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Sample records for model protein rabbit

  1. Transgenic rabbits as therapeutic protein bioreactors and human disease models.

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    Fan, Jianglin; Watanabe, Teruo

    2003-09-01

    Genetically modified laboratory animals provide a powerful approach for studying gene expression and regulation and allow one to directly examine structure-function and cause-and-effect relationships in pathophysiological processes. Today, transgenic mice are available as a research tool in almost every research institution. On the other hand, the development of a relatively large mammalian transgenic model, transgenic rabbits, has provided unprecedented opportunities for investigators to study the mechanisms of human diseases and has also provided an alternative way to produce therapeutic proteins to treat human diseases. Transgenic rabbits expressing human genes have been used as a model for cardiovascular disease, AIDS, and cancer research. The recombinant proteins can be produced from the milk of transgenic rabbits not only at lower cost but also on a relatively large scale. One of the most promising and attractive recombinant proteins derived from transgenic rabbit milk, human alpha-glucosidase, has been successfully used to treat the patients who are genetically deficient in this enzyme. Although the pronuclear microinjection is still the major and most popular method for the creation of transgenic rabbits, recent progress in gene targeting and animal cloning has opened new avenues that should make it possible to produce transgenic rabbits by somatic cell nuclear transfer in the future. Based on a computer-assisted search of the studies of transgenic rabbits published in the English literature here, we introduce to the reader the achievements made thus far with transgenic rabbits, with emphasis on the application of these rabbits as human disease models and live bioreactors for producing human therapeutic proteins and on the recent progress in cloned rabbits.

  2. The transgenic rabbit as model for human diseases and as a source of biologically active recombinant proteins.

    Science.gov (United States)

    Bosze, Zs; Hiripi, L; Carnwath, J W; Niemann, H

    2003-10-01

    Until recently, transgenic rabbits were produced exclusively by pronuclear microinjection which results in additive random insertional transgenesis; however, progress in somatic cell cloning based on nuclear transfer will soon make it possible to produce rabbits with modifications to specific genes by the combination of homologous recombination and subsequent prescreening of nuclear donor cells. Transgenic rabbits have been found to be excellent animal models for inherited and acquired human diseases including hypertrophic cardiomyopathy, perturbed lipoprotein metabolism and atherosclerosis. Transgenic rabbits have also proved to be suitable bioreactors for the production of recombinant protein both on an experimental and a commercial scale. This review summarizes recent research based on the transgenic rabbit model.

  3. Differentially expressed proteins on postoperative 3 days healing in rabbit Achilles tendon rupture model after early kinesitherapy

    Institute of Scientific and Technical Information of China (English)

    Ainuer Jialili; Haxiaobieke Kasimu; Jiasharete Jielile; Shajidan Abudoureyimu; Gulnur Sabirhazi; Darebai Redati; Bai Jingping; Bin Liang; Sailike Duisabai; Jiangaguli Aishan

    2011-01-01

    , peroxiredoxin 1, alpha-1-antiproteinase E a-1and MAD2L1 binding protein, etc. And some with the molecular chaperone, oxidative stress, energy metabolism,signal transduction, coupled with the tendon cell expression and protein synthesis, proliferate, differentiate and are closely related to the AT healing. The GAPDH protein was further validated through Western blotting. It was indicated that some differentially expressed proteins were involved in various metabolism pathways and may play an important role in initial healing of AT rupture.Conclusion: Differentially expressed proteins in rabbit healing AT model may contribute to 3 days healing of AT rupture through a new mechanobiological mechanism due to the application of postoperative early kinesitherapy.

  4. Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on vertebral in the rabbit model of osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Jie Zhang; Yu-Ming Chen; Chen Sheng-Guo; Kaken Habaerxi; Shawuti Alimujiang; Yu Chen; Ming-Zhen Peng; Rong Yue; Yu-Lian Wu; De-Quan Wang

    2014-01-01

    Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of48NewZealand white rabbits were randomly divided into groupⅠ(blank control group), group Ⅱ(CSC injection group), group Ⅲ(CSC/bBMP injection group) and control group.White rabbit osteoporosis model was established rapidly by using castration method+methylprednisolone candidate.After modeling, groups Ⅱ, Ⅲ were given corresponding vertebral body injection material, and4 animals were sacrificed respectively at24 h,6 weeks,12 weeks after vertebral plasty.Tissue pathological status, vertebral mineral density and vertebral body bone mechanical strength were observed.Results:Vertebral body structure form was normal in the groups Ⅱand Ⅲ.Trabecular bone coarsens, connection and repair were observed in micro fracture and bone defects, bone trabecular connectivity was superior to group Ⅰ significantly; vertebral body compression strength in the groupⅠ was on the decline, vertebral compression strength in the groups Ⅱand Ⅲ was on the rise, the largest vertebra.PostoperativeBMC andBMD in groups Ⅱand Ⅲ were incresed, andsignificantly higher than group Ⅰ after6 weeks(P<0.05),BMC and BMD in group Ⅲ after12 weeks were higher than the other three groups.Conclusion:Compound bBMPCSC has good bone induction.It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula, and can significantly improve the vertebral strength, as a vertebral packing material with good application prospect.

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

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    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

  6. Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model.

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    Xulin Xu

    Full Text Available Clinical trials and epidemiological studies have suggested that dietary fish oil (FO supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography-mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of rabbit hearts. Left ventricular myocytes were used in current and voltage clamp experiments to monitor action potentials and ionic currents, respectively. Action potentials of myocytes from FO-fed rabbits exhibited much more positive plateau voltages and prolonged durations. These changes could be explained by an increase in the L-type Ca current (I(CaL and a decrease in the transient outward current (I(to in these myocytes. FO feeding did not change the delayed rectifier or inward rectifier current. Immunoblot experiments showed that the FO-feeding induced changes in I(CaL and I(to were associated with corresponding changes in the protein levels of major pore-forming subunits of these channels: increase in Cav1.2 and decrease in Kv4.2 and Kv1.4. There was no change in other channel subunits (Cav1.1, Kv4.3, KChIP2, and ERG1. We conclude that long-term fish oil supplementation can impact on cardiac electrical activity at least partially by changing channel subunit expression in cardiac myocytes.

  7. Recombinant nAG (a Salamander-Derived Protein Decreases the Formation of Hypertrophic Scarring in the Rabbit Ear Model

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    Mohammad M. Al-Qattan

    2014-01-01

    Full Text Available 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.

  8. Effect of gene modified mesenchymal stem cells overexpression human receptor activity modified protein 1 on inflammation and cardiac repair in a rabbit model of myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    赵然尊

    2012-01-01

    Objective To investigate the effect of mesenchymal stem cells(MSCs) overexpressing human receptor activity modified protein 1(hRAMP1) by adenovirus vector on infarction related inflammation and cardiac repair in a rabbit model of myocardial infarction(MI)

  9. β3-Adrenoceptor Mediates Metabolic Protein Remodeling in a Rabbit Model of Tachypacing-Induced Atrial Fibrillation

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    Yixi Liu

    2013-12-01

    Full Text Available Background: The beta 3-adrenoceptor (β3-AR is closely associated with energy metabolism. This study aimed to explore the role of β3-AR in energy remodeling in a rabbit model of pacing-induced atrial fibrillation (AF. Methods: Rabbits with a sham-operation or pacing-induced AF were used for this study, and the latter group was further divided into three subgroups: 1 the pacing group, 2 the β3-AR agonist (BRL37344-treated group, and 3 the β3-AR antagonist (SR59230A-treated group. Atrial electrogram morphology and surface ECG were used to monitor the induction of AF and atrial effective refractory period (AERP. RT-PCR and western blot (WB were used to show alterations in β3-AR and metabolic-related protein. Results: RT-PCR and WB results showed that β3-AR was significantly upregulated in the pacing group, and that it corresponded with high AF inducibility and significantly decreased AERP200 and ATP production in this group. Inhibition of β3-AR decreased the AF induction rate, reversed AERP200 reduction, and restored ATP levels in the AF rabbits. Further activation of β3-AR using agonist BRL37344 exacerbated AF-induced metabolic disruption. Periodic acid Schiff (PAS and Oil Red O staining showed β3-AR-dependent glycogen and lipid droplet accumulation in cardiac myocytes with AF. Glucose transporter-4 (GLUT-4 and CD36, key transporters of glucose and fatty acids, were downregulated in the pacing group. Expression of carnitine-palmitoyltransferase I (CPT-1, a key regulator in fatty acid metabolism, was also significantly downregulated in the pacing group. Reduced glucose transportation and fatty acid oxidation could be restored by inhibition of β3-AR. Furthermore, key regulators of metabolism, peroxisome proliferator-activated receptor-α (PPARα and PPAR co-activator (PGC-1α can be regulated by pharmacological intervention of the β3-AR. Conclusions: β3-AR is involved in metabolic protein remodeling in AF. PPARα/PGC-1α signaling pathway

  10. Rabbit trochlear model of osteochondral allograft transplantation.

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    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

    2011-10-01

    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft-host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host-graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host-graft bone interface available for analysis.

  11. Differential protein expression in spinal cord tissue of a rabbit model of spinal cord ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Qi Gao; Jian Dong; Jianhang Jiao; Yonghui Liang; Xiaoyu Yang; Guifeng Liu; Xiaoxue Li; Benqing Zhu; Jian Liu; Maoguang Yang; Weiwei Xia

    2012-01-01

    New Zealand rabbits were randomly divided into an ischemia group (occlusion of the abdominal aorta for 60 minutes), an ischemia-reperfusion group (occlusion of the abdominal aorta for 60 minutes followed by 48 hours of reperfusion) and a sham-surgery group. Two-dimensional gel electrophoresis detected 49 differentially expressed proteins in spinal cord tissue from the ischemia and ischemia/reperfusion groups and 23 of them were identified by mass spectrometry. In the ischemia group, the expression of eight proteins was up regulated, and that of the remaining four proteins was down regulated. In the ischemia/reperfusion group, the expression of four proteins was up regulated, and that of two proteins was down regulated. In the sham-surgery group, only one protein was detected. In the ischemia and ischemia/reperfusion groups, four proteins overlapped between groups with the same differential expression, including three that were up regulated and one down regulated. These proteins were related to energy metabolism, cell defense, inflammatory mechanism and cell signaling.

  12. Roles of monocyte chemotactic protein 1 and nuclear factor-κB in immune response to spinal tuberculosis in a New Zealand white rabbit model

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    Guo, X.H.; Bai, Z.; Qiang, B.; Bu, F.H.; Zhao, N.

    2017-01-01

    This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis. PMID:28225889

  13. Auxiliary proteins that facilitate formation of collagen-rich deposits in the posterior knee capsule in a rabbit-based joint contracture model.

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    Steplewski, Andrzej; Fertala, Jolanta; Beredjiklian, Pedro K; Abboud, Joseph A; Wang, Mark L Y; Namdari, Surena; Barlow, Jonathan; Rivlin, Michael; Arnold, William V; Kostas, James; Hou, Cheryl; Fertala, Andrzej

    2016-03-01

    Post-traumatic joint contracture is a debilitating consequence of trauma or surgical procedures. It is associated with fibrosis that develops regardless of the nature of initial trauma and results from complex biological processes associated with inflammation and cell activation. These processes accelerate production of structural elements of the extracellular matrix, particularly collagen fibrils. Although the increased production of collagenous proteins has been demonstrated in tissues of contracted joints, researchers have not yet determined the complex protein machinery needed for the biosynthesis of collagen molecules and for their assembly into fibrils. Consequently, the purpose of our study was to investigate key enzymes and protein chaperones needed to produce collagen-rich deposits. Using a rabbit model of joint contracture, our biochemical and histological assays indicated changes in the expression patterns of heat shock protein 47 and the α-subunit of prolyl 4-hydroxylase, key proteins in processing nascent collagen chains. Moreover, our study shows that the abnormal organization of collagen fibrils in the posterior capsules of injured knees, rather than excessive formation of fibril-stabilizing cross-links, may be a key reason for observed changes in the mechanical characteristics of injured joints. This result sheds new light on pathomechanisms of joint contraction, and identifies potentially attractive anti-fibrotic targets. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  14. Purification and characterization of protein Z from rabbit liver cytosol.

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    Vincent, S H; Holeman, B; Muller-Eberhard, U

    1985-10-30

    Protein Z was purified from rabbit liver cytosol by affinity chromatography on oleic acid-agarose and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After removal of sodium dodecyl sulfate, the renatured protein was found to bind heme and bilirubin with a Kd of approximately 1 microM which produced large red shifts in their absorption spectra. On isoelectric focusing, rabbit protein Z exhibited two main bands with pI around 6.0.

  15. Review of experimental models: sinusitis in rabbits

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    André Coura Perez

    2014-10-01

    Full Text Available INTRODUCTION: In order to better understand the pathophysiology of rhinosinusitis, several attempts have been made to create the disease in an animal model. Among the studied rodents each has its advantages and disadvantages. Rabbits are considered more appropriate for studies that require surgical manipulation or invasive procedures. OBJECTIVES: To evaluate the most viable experimental model of rhinosinusitis in rabbits to be adopted in future studies. METHODS: An electronic search for studies with experimental models of rhinosinusitis in rabbits published in English and Portuguese between July of 1967 and January of 2013 was conducted in Medline, Pub Med, Cochrane, and CAPES databases, using the keywords "sinusitis", "rabbits", and "polyps". RESULTS: A total of 256 studies were retrieved, but in accordance with the inclusion and exclusion criteria, only ten studies were selected. Many different methods of response assessment were used in these studies. CONCLUSION: To date, there is no ideal experimental model for induction of acute or chronic rhinosinusitis in rabbits, but the rhinogenic model appears to be the most viable option for the continuity of studies of the disease.

  16. Increased expression and local accumulation of the Prion Protein, Alzheimer Aβ peptides, superoxide dismutase 1, and Nitric oxide synthases 1 & 2 in muscle in a rabbit model of diabetes

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    Bitel Claudine L

    2010-09-01

    Full Text Available Abstract Background Muscle disease associated with different etiologies has been shown to produce localized accumulations of amyloid and oxidative stress-related proteins that are more commonly associated with neurodegeneration in the brain. In this study we examined changes in muscle tissue in a classic model of diabetes and hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Aβ peptides, the prion protein (PrP, and superoxide dismutase 1 (SOD1, as well as nitric oxide synthases is produced in muscle in diabetic animals. This wild-type rabbit model includes systemic physiological expression of human-like Alzheimer precursor proteins and Aβ peptides that are considered key in Alzheimer protein studies. Results Diabetes was produced in rabbits by injection of the toxic glucose analogue alloxan, which selectively enters pancreatic beta cells and irreversibly decreases insulin production, similar to streptozotocin. Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia were analyzed with biochemical and in situ methods. Immunoblots of whole muscle protein samples demonstrated increased PrP, SOD1, as well as neuronal and inducible Nitric oxide synthases (NOS1 and NOS2 in diabetic muscle. In contrast, we detected little change in Alzheimer Aβ precursor protein expression, or BACE1 and Presenilin 1 levels. However, Aβ peptides measured by ELISA increased several fold in diabetic muscle, suggesting a key role for Aβ cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model. Histological changes in diabetic muscle included localized accumulations of PrP, Aβ, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell infiltration. Conclusions The present study provides evidence that several classic amyloid and oxidative stress-related disease proteins coordinately increase in overall expression and form localized accumulations in diabetic muscle. The present study

  17. Plasma PIVKA proteins in rabbits given warfarin.

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    Zivelin, A; Rao, L V; Rapaport, S I

    1996-06-01

    The presence of partially carboxylated forms of the vitamin K dependent coagulation factors (PIVKA) was evaluated in the plasma of rabbits treated with warfarin. Excess antigen over activity as measured in rabbit specific assays was taken as evidence for PIVKA. Our data confirm a previous report of the absence of plasma PIVKA prothrombin. In contrast, plasma PIVKA factors VII, IX, and X were demonstrable. A striking excess of plasma factor IX antigen over activity was measured and a large fraction of the factor IX antigen persisted in the plasma after its adsorption with barium citrate.

  18. Overweight in young males reduce fertility in rabbit model

    National Research Council Canada - National Science Library

    Francisco Marco-Jiménez; José Salvador Vicente

    2017-01-01

    ... parameters and fertility success in randomized controlled trial in a rabbit model. Fourteen male rabbits were randomly assigned to a control group in which nutritional requirements were satisfied or a group fed...

  19. Habitat Suitability Index Models: Swamp rabbit

    Science.gov (United States)

    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.

  20. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    OpenAIRE

    Bertagnoli, Stéphane; Gelfi, Jacqueline; Le Gall, Ghislaine; Boilletot, Eric; Vautherot, Jean-François; Rasschaert, Denis; Laurent, Sylvie; Petit, Frédérique; Boucraut-Baralon, Corine; Milon, Alain

    1996-01-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma vir...

  1. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    Science.gov (United States)

    Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

    1996-08-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

  2. Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    YANG Xiaoyun; WANG Lin; ZENG Hesong; DUBEY Laxman; ZHOU Ning; PU Jun

    2006-01-01

    To observe the effects of simvastatin on nuclear factor kappaB (NF-κB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects.Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), highcholesterol group (HC), high-cholesterol+ simvastatin group (HC+S) and then were fed for 12weeks. At the end of theexperiment, standard enzymatic assays, electrophoretic mobility shift assay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-κB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-κB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-κB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NFκB-DNA binding activity and by reducing the expression of MCP-1 protein.

  3. Experimental model of bladder instability in rabbits

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    Balasteghin K.T.

    2003-01-01

    Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

  4. A rabbit model of lower eyelid fibrosis.

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    Griepentrog, Gregory J; Park, D J John; Zaldivar, Renzo A; Pulido, Jose S; Cameron, J Douglas; Woog, John J

    2010-01-01

    To create and validate a new model of lower eyelid fibrosis in Dutch-belted rabbits. Five Dutch-belted rabbits were injected with a transcutaneous 1-ml injection of standard 95% ethanol alcohol just inferior to the eyelid margin of one lower eyelid. A control injection of 1 ml of balanced saline solution was given to the opposite eyelid. A small tattoo was placed on the skin overlying the inferior orbital rim and used as a measuring point of reference in relation to the lower eyelid margin. Analysis was twofold: eyelid measurements were made over 8 weeks to determine the presence of eyelid shortening, and a histopathologic analysis was performed. Mean lower eyelid shortening was greater in the ethanol alcohol intervention eyelids than the control group (-3.4 mm +/- 1.67 mm vs. 0.5 mm +/- 0.71 mm, p = 0.01). Histopathologic analysis revealed extensive fibrosis in the ethanol alcohol invention eyelids compared with the control group. Ethanol alcohol induces eyelid fibrosis and lower eyelid shortening. This may be a useful model in the future testing of novel surgical or pharmacologic treatments.

  5. Autoradiographic studies in a rabbit osteoarthrosis model

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    Fengler, H.; Franz, R. (Medizinische Akademie, Dresden (German Democratic Republic))

    1982-02-01

    To study the onset of the osteoarthrotic process, an osteoarthrosis model was used on the knee joint in adult rabbits by a valgus deformity of the proximal tibia of 30/sup 0/ in conformity with Reimann 1973. The synthesis capacity of the chondrocytes was investigated by using /sup 35/S-sulfate autoradiographies. Already prior to the affection of the superficial integrity of the cartilage it was possible to observe an enhanced glycosaminoglycan synthesis, but with progressing fibrillation the sulfate incorporation was found to be diminished. Thanks to autoradiography with /sup 3/H-thymidine the replication of the chondrocytes was already found at very early stages of osteoarthrosis that is likely to occur mitotically. The osteotomy itself induces mitoses and an enhanced glycosaminoglycan synthesis.

  6. GROWTH ANALYSIS IN RABBIT USING GOMPERTZ NON-LINEAR MODEL

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    A. Setiaji

    2014-10-01

    Full Text Available An experiment was conducted to compare the growth curve of rabbit. Three breeds of rabbit,namely Indonesian Local Rabbit (IL, Flamish Giant (FG and Rex (R were used in the study.Individual body weights of each breed was measured from birth to 63 days of age with 3-days interval.Those periodical data were separated into different sex, be then it was averaged to analysis growthpattern. Growth curve parameters were estimated to fit growth data. There was no difference in bodyweight between sexs within breed. Indonesian local rabbit had the lowest body weight. The resultsshowed that growth curve paramaters among three breeds were significantly different (P<0.05 for bothsexes. FG had the highest value of asymptotic mature weight, followed by R and IL. In conclusion,Gompertz model was excellent fit for the growth data in rabbit with a high coefficient determination (R2= 0.999.

  7. Endostatin inhibits hypertrophic scarring in a rabbit ear model*

    OpenAIRE

    Ren, Hai-Tao; Hu, Hang; LI, YUAN; Jiang, Hong-fei; Hu, Xin-lei; Han, Chun-mao

    2013-01-01

    Objective: The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods: Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the cont...

  8. Antigenic structure of the capsid protein of rabbit haemorrhagic disease virus

    DEFF Research Database (Denmark)

    Martinez-Torrecuadrada, Jorge L.; Cortes, Elena; Vela, Carmen;

    1998-01-01

    Rabbit haemorrhagic disease virus (RHDV) causes an important disease in rabbits. The virus capsid is composed of a single 60 kDa protein. The capsid protein gene was cloned in Escherichia coli using the pET3 system, and the antigenic structure of RHDV VP60 was dissected using 11 monoclonal...

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jiahui Yang

    of diseases such as SLE with familial patterns of inheritance. Although no consistent pattern of elevated expression of BAFF mRNA or protein was found in the rabbits studied, the data collected and reported here build upon previous data to refine understanding of a rabbit model of SLE.

  12. Experimental model of cutaneous radiation injury in rabbits

    OpenAIRE

    Meirelles,Rafael Panisi de Campos; Hochman, Bernardo; Helene Junior,Americo; Lellis,Rute; Fraga, Murillo Francisco Pires; Ferreira, Lydia Masako

    2013-01-01

    PURPOSE: To describe an experimental model of cutaneous radiation injury in rabbits. METHODS: On this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. RESULTS: Af...

  13. Acute propranolol infusion stimulates protein synthesis in rabbit skin wound.

    Science.gov (United States)

    Zhang, Xiao-Jun; Meng, Chengyue; Chinkes, David L; Finnerty, Celeste C; Aarsland, Asle; Jeschke, Marc G; Herndon, David N

    2009-05-01

    Propranolol administration has been demonstrated to improve cardiac work, decrease energy expenditure, and attenuate lipolysis in burned patients; however, its effect on wound healing has not been reported. In rabbits, a partial-thickness skin donor site wound was created on the back, and catheters were placed in the carotid artery and jugular vein. A nasogastric feeding tube was placed for enteral feeding. On day 5 after injury, stable isotope tracers were infused to determine protein and DNA kinetics in the wound. Propranolol hydrochloride was injected in 1 group during the tracer infusion to decrease heart rate, and the other group without propranolol injection served as a control. The propranolol infusion decreased heart rate by 21%. The protein fractional synthetic rate in the wound was greater in the propranolol group (8.6 +/- 0.9 vs 6.1 +/- 0.5%/day, P synthesis - breakdown) was increased in the propranolol group (5.0 +/- 1.2 vs 2.8 +/- 0.7%/day, P = .07). Wound DNA fractional synthetic rates were comparable. The protein fractional synthetic rate was correlated with percent decrease in heart rate, but expression of the beta-adrenergic receptors and downstream signaling cascades in local wounds were not affected after propranolol treatment. Propranolol infusion increased wound protein synthetic rate and tended to increase wound protein deposition rate, which might be beneficial to wound healing. These changes might reflect a systemic response to the beta-adrenergic blockade.

  14. INFLUENCE OF NATURAL IMMUNOMODULATORS ON PROTEIN FRACTIONS AND CORTISOL CONTENT IN RABBIT BLOOD UNDER STRESS

    Directory of Open Access Journals (Sweden)

    Grabovskyi S.

    2015-08-01

    Full Text Available The results of determination of protein fractions, cortisol content in blood of rabbits, which further added to the feed of natural origin biologically active substances are presented in the article. As an antistressors and immunomodulators in pre-slaughter period are using of spleen extract biologically active substances were obtained with ultrasound application. The purpose of research — determination of changes of protein fractions, cortisol content in rabbits blood before slaughter and their correction of natural origin biologically active substances (spleen extract. Object and research methods. The experiment was conducted on 15 rabbits with standard diet. Three groups of rabbits five month of age (5 rabbits each was formed for research. The spleen extract were using as an biologically active substances to the feed rabbits in pre-slaughter period (five days before slaughter. The extracts were applied to feed by aerosol method (70 °alcohol solution of spleen extract volume of 1.4 ml per rabbit (group I. The rabbits (group II received to the feed in the same way of 70 °alcohol solution in the same volume. The control group rabbits received the standard feed in the same volume. The feed eating by rabbits was exercised daily. The rabbits ate food completely. The rabbits slaughter was carried out in the morning. The blood plasma protein fractions separation was carried out by horizontal electrophoresis in polyacrylamide gel (PAAG. Mathematical treatment of the research results worked statistically using the software package Statistica 6.0 and Microsoft Excel for Windows XP. Probability differences was assessed by Student t-test and results considered likely at P ≤ 0.05. Results and discussion. We measured the ratio of blood plasma protein fractions of rabbits, which in addition to the feed fed of natural origin biologically active substances. As a result of research was found that aerosol introduction of the spleen extract to the rabbits

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

    Science.gov (United States)

    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 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.

  16. Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits

    Directory of Open Access Journals (Sweden)

    Martin Ungerer

    2012-06-01

    Full Text Available The ABCG1 protein is centrally involved in reverse cholesterol transport from the vessel wall. Investigation of the effects of ABCG1 overexpression or knockdown in vivo has produced controversial results and strongly depended on the gene intervention model in which it was studied. Therefore, we investigated the effect of local overexpression of human ABCG1 in a novel model of vessel wall-directed adenoviral gene transfer in atherosclerotic rabbits. We conducted local, vascular-specific gene transfer by adenoviral delivery of human ABCG1 (Ad-ABCG1-GFP in cholesterol-fed atherosclerotic rabbits in vivo. Endothelial overexpression of ABCG1 markedly reduced atheroprogression (plaque size and almost blunted vascular inflammation, as shown by markedly reduced macrophage and smooth muscle cell invasion into the vascular wall. Also endothelial function, as determined by vascular ultrasound in vivo, was improved in rabbits after gene transfer with Ad-ABCG1-GFP. Therefore, both earlier and later stages of atherosclerosis were improved in this model of somatic gene transfer into the vessel wall. In contrast to results in transgenic mice, overexpression of ABCG1 by somatic gene transfer to the atherosclerotic vessel wall results in a significant improvement of plaque morphology and composition, and of vascular function in vivo.

  17. Deterministic Models of Inhalational Anthrax in New Zealand White Rabbits

    Science.gov (United States)

    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. PMID:24527843

  18. Rabbit as an animal model for experimental research.

    Science.gov (United States)

    Mapara, Manjeet; Thomas, Betsy Sara; Bhat, K M

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. Though experimentation on rabbits seems to be easy there are many pitfalls. Our endeavor in this article is to integrate all the data about maintaining rabbits as a model and to critically analyze it on the basis of our experimentation.

  19. Immunopotentiation of outer membrane protein through anti-idiotype Pasteurella multocida vaccine in rabbits.

    Science.gov (United States)

    Arif, Javid; Rahman, Sajjad-Ur; Arshad, Muhammad; Akhtar, Pervez

    2013-11-01

    Pasteurella multocida was isolated from cattle affected with haemorrhagic septicaemia and characterized on the basis of morphological, cultural and biochemical tests. Bacterial outer membrane proteins (OMPs) were extracted with 1% Sarkosyl method. P. multocida anti-idiotype vaccine prepared from OMPs (21.3 mg per 100 ml), was evaluated and compared with bacterin supplemented with 10% OMPs and plain alum-adsorbed bacterin in rabbit models. It was observed that OMPs-anti-idiotype vaccine induced high levels of antibody titres (geomean titres -GMT) detected using indirect haemagglutination (IHA) test. The OMPs anti-idiotype antibody titres of 168.9 GMT were obtained to 42.2 GMT in OMPs supplemented bacterin on 21 days post vaccination, while the plain bacterin had the least titre of 27.9 GMT. The OMPs-anti-idiotype vaccine provoked better immunogenic response in terms of highest GMT titres and long lasting effect in rabbits and 100% protection against the challenge with homologous strain of P. multocida,while 88% protection was obtained in rabbits, given OMPs supplemented bacterin.

  20. Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is the functional homologue for human CXCL6.

    Science.gov (United States)

    Catusse, Julie; Struyf, Sofie; Wuyts, Anja; Weyler, Myke; Loos, Tamara; Gijsbers, Klara; Gouwy, Mieke; Proost, Paul; Van Damme, Jo

    2004-11-15

    Neutrophil chemotactic protein (NCP) is a rabbit CXC chemokine with activating and chemotactic properties on neutrophilic granulocytes. Although its selective activity on neutrophils is demonstrated, its interactions with specific chemokine receptors are not defined. For further functional characterization, NCP was chemically synthesized and was found to be equipotent as natural NCP in neutrophil chemotaxis. To identify its human homologue, we separately expressed two potential rabbit NCP receptors (CXCR1 and CXCR2) in Jurkat cells. Pure synthetic NCP was equally efficient to promote chemotaxis through either rabbit CXCR1 or CXCR2. Moreover, chemotaxis assays on rabbit CXCR1 and CXCR2 transfectants showed that NCP uses the same receptors as interleukin-8 (IL-8), a major rabbit CXC chemokine, but not rabbit GROalpha, which only recognized CXCR2. In addition, specific inhibitors for CXCR1 or CXCR2 reduced rabbit neutrophil chemotaxis induced by NCP and rabbit IL-8. Furthermore, NCP and the structurally related human CXCR1/CXCR2 agonist CXCL6/GCP-2 (granulocyte chemotactic protein-2) cross-desensitized each other in intracellular calcium release assays on human neutrophils, further indicating that both chemokines share the same receptors. The inflammatory role of NCP was also evidenced by its potent granulocytosis inducing capacity in rabbits upon systemic administration. This study provides in vitro and in vivo evidences that NCP is the functional rabbit homologue for human CXCL6/GCP-2 rather than the most related CXCR2 agonist CXCL5/ENA-78 (epithelial cell-derived neutrophil activating peptide-78). It is concluded that the rabbit is a better model to study human neutrophil activation compared to mice, which lack CXCL8/IL-8.

  1. The rabbit as an experimental model in laryngology

    Directory of Open Access Journals (Sweden)

    Carneiro, Christiano de Giacomo

    2009-06-01

    Full Text Available Introduction: In the research in laryngology we normally use animal models. The animal experimentation may also contribute largely for this evolution, mainly for the easy access compared to human larynxes and for they are more easily controlled. Objective: The objective of this work is to analyze the laryngofissure with vocal cords graft as an experimental surgical technique in male adult rabbits. Method: We studied 46 New Zealand albino rabbits submitted to microsurgery in both vocal cords with autologous unilateral or bilateral graft of fat or fascia. Results: There were 4 losses of 3 animals until the first week of the postoperative period and another after 19 days after surgery. In the subsequent animals there were no infection, hematoma or sutures dehiscence. Conclusion: The study enables the conclusion that the experimental laryngofissure in rabbits is a safe method that may be used for laryngological studies.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  5. Brain death induces the alteration of liver protein expression profiles in rabbits.

    Science.gov (United States)

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  6. The use of rabbits in atherosclerosis research. Diet and drug intervention in different rabbit models exposed to selected dietary fats and the calcium antagonist (-)-anipamil

    DEFF Research Database (Denmark)

    Mortensen, Alicja

    Laboratory animal models play an important role in atherosclerosis research. One of the most popular laboratory animal species in this field of research is the rabbit. The rabbit fulfils most of the criteria for an animal model for human atherosclerosis. Three rabbit models were established...

  7. A Human-Type Nonalcoholic Steatohepatitis Model with Advanced Fibrosis in Rabbits

    Science.gov (United States)

    Ogawa, Tomohiro; Fujii, Hideki; Yoshizato, Katsutoshi; Kawada, Norifumi

    2010-01-01

    Nonalcoholic steatohepatitis (NASH) progresses to liver fibrosis and cirrhosis, which can lead to life-threatening liver failure and the development of hepatocellular carcinoma. The aim of the present study was to create a rabbit model of NASH with advanced fibrosis (almost cirrhosis) by feeding the animals a diet supplemented with 0.75% cholesterol and 12% corn oil. After 9 months of feeding with this diet, the rabbits showed high total cholesterol levels in serum and liver tissues in the absence of insulin resistance. The livers became whitish and nodular. In addition, the number of rabbit macrophage antigen-positive cells and the expression of mRNAs for inflammatory cytokines showed a significant increase. Moreover, fibrotic septa composed of collagens and α-smooth muscle actin-positive cells were found between the central and portal veins, indicating alteration of the parenchymal architecture. There was also a marked increase of mRNAs for transforming growth factor-β1 and collagen 1A1. Comprehensive analysis of protein and gene expression revealed an imbalance of the antioxidant system and methionine metabolism. We also found that ezetimibe attenuated steatohepatitis in this model. In conclusion, the present rabbit model of NASH features advanced fibrosis that is close to cirrhosis and may be useful for analyzing the molecular mechanisms of human NASH. Ezetimibe blunted the development of NASH in this model, suggesting its potential clinical usefulness for human steatohepatitis. PMID:20489159

  8. Experimental Study on the Preventive Mechanism of Salviae Miltiorrhizae Against Atherosclerosis in Rabbits Models

    Institute of Scientific and Technical Information of China (English)

    李树生; 万磊

    2004-01-01

    Summary: The preventive mechanism of salviae miltiorrhizae (SM) against experimental atherosclerosis (AS) in rabbits models was investigated. The experimental AS rabbit models were reproduced by feeding the high cholesterol diet. The changes of atherosclerotic plaques in normal group, model group and SM treated group were observed. The levels of serum TG, TC, HDL-C and LDL-C were determined. The immunohistochemistry was used to detect the expression of Bcl-2,Bax and IL-6 proteins in atherosclerotic plaques. The results showed that the level of serum TG in SM treated group was significantly lower than in model group (P<0.01). Immunohistochemistry revealed that the expression of Bcl-2, Bax ano IL-6 in model group was significantly higher than in normal group.In the SM group, the expression of Bcl-2 protein was up-regulated and that of Bax was down-regulated. It was suggested that SM could inhibit formation of AS in experimental rabbits. To decrease the expression of Bax and increase the expression of Bcl-2 protein may be one of the mechanisms of SM against atherosclerosis.

  9. Ocular hypotensive effects of a Rho-associated protein kinase inhibitor in rabbits

    Directory of Open Access Journals (Sweden)

    Kamaruddin MI

    2017-03-01

    Full Text Available Muhammad Irfan Kamaruddin,1,2 Momoko Nakamura-Shibasaki,1 Yu Mizuno,1 Yoshiaki Kiuchi1 1Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Ophthalmology, Hasanuddin University, Makassar, South Sulawesi, Indonesia Purpose: Ripasudil is a novel Rho-associated protein kinase inhibitor that is used to treat ocular hypertension. However, the comparison of the intraocular pressure (IOP-lowering effects between ripasudil alone and other ocular hypotensive drugs has not been studied thoroughly. The purpose of this study is to examine the ocular hypotensive effects of 0.4% ripasudil, 2% pilocarpine, 0.5% timolol and 0.1% dorzolamide in rabbits. We also studied the IOP changes when 0.4% ripasudil was combined with 2% pilocarpine, 0.5% timolol or 0.1% dorzolamide. Methods: One drop of saline solution, 0.4% ripasudil, 0.5% timolol, 2% pilocarpine or 1% dorzolamide or a combination of these agents was applied topically to the left eyes of eight healthy albino rabbits. Posttreatment changes in the IOP of albino rabbits were monitored using a rebound tonometer over a 5-h time course. Changes in IOP after application of saline served as the control. One-way analysis of variance and Dunnett’s post hoc tests were used for statistical analyses. Results: After topical instillation, 0.4% ripasudil resulted in significant decreases in IOP at 0.5 and 1 h compared with the control group. Treatment with timolol, pilocarpine or dorzolamide had no significant effect on IOP. Treatment with timolol, pilocarpine or dorzolamide in combination with ripasudil resulted in significant reductions in IOP at 1 h. However, none of these agents enhanced the IOP-lowering effects of ripasudil. Conclusion: Ripasudil has stronger IOP-lowering effects than timolol, pilocarpine or dorzolamide hypotensive agents in our rabbit model. Addition of timolol, pilocarpine or dorzolamide did not enhance

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  12. The rabbit pup, a natural model of nursing anticipatory activity

    Science.gov (United States)

    Caba, Mario; González-Mariscal, Gabriela

    2009-01-01

    Mother rabbits nurse their young once a day with circadian periodicity. Nursing bouts are brief (ca. 3 min) and occur inside the maternal burrow. Despite this limited contact mother rabbits and their pups are tuned to each other to ensure that the capacities of each party are used efficiently to ensure the weaning of a healthy litter. In this review we present behavioral, hormonal, metabolic and hormonal correlates of this phenomenon in mother rabbits and their pups. Research is revealing that the circadian rhythm of locomotion shifts in parallel to the timing of nursing in both parties. In pups corticosterone has a circadian rhythm with highest levels at the time of nursing. Other metabolic and hormonal parameters follow an exogenous or endogenous rhythm which is affected by the time of nursing. In the brain clock genes (e.g., Per1) are differentially expressed in specific brain regions (e.g., suprachiasmatic nucleus, paraventricular nucleus) in relation to providing or ingesting milk in mothers and young, respectively. These findings suggest that circadian activities are modulated, in the mothers, by suckling stimulation and, in the young, by the ingestion of milk and/or the perception of the mammary pheromone. In conclusion the rabbit pup is an extraordinary model for studying the entraining by a single daily food pulse with minimal manipulations. The mother offers the possibility of studying nursing as a non-photic synchronizer, also with minimal manipulation, as suckling stimulation from the litter occurs only once daily PMID:19863657

  13. Rabbit as an animal model for experimental research

    OpenAIRE

    Manjeet Mapara; Betsy Sara Thomas; Bhat, K. M.

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. T...

  14. Rabbit as an animal model for experimental research

    OpenAIRE

    Manjeet Mapara; Betsy Sara Thomas; Bhat, K. M.

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. T...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  18. Rabbit Hemorrhagic Disease Virus Variant Recombinant VP60 Protein Induces Protective Immunogenicity.

    Science.gov (United States)

    Yang, Dong-Kun; Kim, Ha-Hyun; Nah, Jin-Ju; Song, Jae-Young

    2015-11-01

    Rabbit hemorrhagic disease virus (RHDV) is highly contagious and often causes fatal disease that affects both wild and domestic rabbits of the species Oryctolagus cuniculus. A highly pathogenic RHDV variant (RHDVa) has been circulation in the Korean rabbit population since 2007 and has a devastating effect on the rabbit industry in Korea. A highly pathogenic RHDVa was isolated from naturally infected rabbits, and the gene encoding the VP60 protein was cloned into a baculovirus transfer vector and expressed in insect cells. The hemagglutination titer of the Sf-9 cell lysate infected with recombinant VP60 baculovirus was 131,072 units/50 μl and of the supernatant 4,096 units/50 μl. Guinea pigs immunized twice intramuscularly with a trial inactivated RHDVa vaccine containing recombinant VP60 contained 2,152 hemagglutination inhibition (HI) geometric mean titers. The 8-week-old white rabbits inoculated with one vaccine dose were challenged with a lethal RHDVa 21 days later and showed 100% survival rates. The recombinant VP60 protein expressed in a baculovirus system induced high HI titers in guinea pigs and rendered complete protection, which led to the development of a novel inactivated RHDVa vaccine.

  19. Protein changes in the retina following experimental retinal detachment in rabbits

    DEFF Research Database (Denmark)

    Mandal, Nakul; Lewis, Geoffrey P; Fisher, Steven K

    2011-01-01

    Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most...

  20. The rabbit pup, a natural model of nursing-anticipatory activity.

    Science.gov (United States)

    Caba, Mario; González-Mariscal, Gabriela

    2009-11-01

    Mother rabbits nurse their young once a day with circadian periodicity. Nursing bouts are brief (ca. 3 min) and occur inside the maternal burrow. Despite this limited contact mother rabbits and their pups are tuned to each other to ensure that the capacities of each party are used efficiently to ensure the weaning of a healthy litter. In this review we present behavioral, metabolic and hormonal correlates of this phenomenon in mother rabbits and their pups. Research is revealing that the circadian rhythm of locomotion shifts in parallel to the timing of nursing in both parties. In pups corticosterone has a circadian rhythm with highest levels at the time of nursing. Other metabolic and hormonal parameters follow an exogenous or endogenous rhythm which is affected by the time of nursing. In the brain, clock genes and their proteins (e.g. Per1) are differentially expressed in specific brain regions (e.g. suprachiasmatic nucleus, paraventricular nucleus) in relation to providing or ingesting milk in mothers and young, respectively. These findings suggest that circadian activities are modulated, in the mothers, by suckling stimulation and, in the young, by the ingestion of milk and/or the perception of the mammary pheromone. In conclusion, the rabbit pup is an extraordinary model for studying the entraining by a single daily food pulse with minimal manipulations. The mother offers the possibility of studying nursing as a non-photic synchronizer, also with minimal manipulation, as suckling stimulation from the litter occurs only once daily.

  1. Rabbit serum amyloid protein A: expression and primary structure deduced from cDNA sequences.

    Science.gov (United States)

    Rygg, M; Marhaug, G; Husby, G; Dowton, S B

    1991-12-01

    Serum amyloid A protein (SAA), the precursor of amyloid protein A (AA) in deposits of secondary amyloidosis, is an acute phase plasma apolipoprotein produced by hepatocytes. The primary structure of SAA demonstrates high interspecies homology. Several isoforms exist in individual species, probably with different amyloidogenic potential. The nucleotide sequences of two different rabbit serum amyloid A cDNA clones have been analysed, one (corresponding to SAA1) 569 base pairs (bp) long and the other (corresponding to SAA2) 513 bp long. Their deduced amino acid sequences differ at five amino acid positions, four of which are located in the NH2-terminal region of the protein. The deduced amino acid sequence of SAA2 corresponds to rabbit protein AA previously described except for one amino acid in position 22. Eighteen hours after turpentine stimulation, rabbit SAA mRNA is abundant in liver, while lower levels are present in spleen. None of the other extrahepatic organs studied showed any SAA mRNA expression. A third mRNA species (1.9 kb) hybridizing with a single-stranded RNA probe transcribed from the rabbit SAA cDNA, was identified. SAA1 and SAA2 mRNA were found in approximately equal amounts in turpentine-stimulated rabbit liver, but seem to be coordinately decreased after repeated inflammatory stimulation.

  2. Experimental model of cutaneous radiation injury in rabbits.

    Science.gov (United States)

    Meirelles, Rafael Panisi de Campos; Hochman, Bernardo; Helene Junior, Americo; Lellis, Rute; Fraga, Murillo Francisco Pires; Ferreira, Lydia Masako

    2013-11-01

    To describe an experimental model of cutaneous radiation injury in rabbits. On this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5 kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. After 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000 cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. The proposed experimental model is reproductable. This study suggests that the dosage 4500 cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits.

  3. Experimental model of cutaneous radiation injury in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

    2013-07-01

    Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

  4. Rabbit model of radiation-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zong Du; Hua Ren; Jian-Fei Song; Li-Fei Zhang; Feng Lin; Hai-Yong Wang

    2013-01-01

    Objective:To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury.Methods:Twenty-eightNewZealand white rabbits were randomly divided into3 groups(the right lung irradiation group, the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwentCT and pathological examinations at1,2,4,8,12,16 weeks, respectively after radiation.Results:Within4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At8-12 weeks after irradiation,CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

  5. Ultrastructural immunohistochemical localization of Clara cell secretory protein in pulmonary epithelium of rabbits.

    OpenAIRE

    Patton, S E; Gupta, R. P.; Nishio, S.; Eddy, E M; Jetten, A. M.; Plopper, C. G.; Nettesheim, P; Hook, G E

    1991-01-01

    Highly purified Clara cells (93 +/- 3%) isolated from the lungs of rabbits were used to produce an antiserum against Clara cell secretory proteins. This antiserum was used to identify and study the biosynthesis and secretion of [35S]methionine-labeled proteins from isolated Clara cells. The antiserum recognized one major secretory protein with apparent molecular weight of 6 kDa and reacted weakly with a higher molecular weight protein of about 180 kDa. Biosynthesis and secretion of these prot...

  6. Laser facial nerve welding in a rabbit model.

    Science.gov (United States)

    Bloom, Jason D; Bleier, Benjamin S; Goldstein, Stephen A; Carniol, Paul J; Palmer, James N; Cohen, Noam A

    2012-01-01

    To assess the feasibility of laser tissue welding for repair of facial nerve injury. In a prospective in vivo animal survival surgery model, rabbit facial nerve injury was followed by either standard suture neurorrhaphy or laser tissue welding using a diode laser (808 ± 1 nm) to weld biological solder. Rabbits were evaluated at 4, 8, 12, and 16 weeks by facial videography and electromyography. Histopathological analysis of the repair was performed at 4 and 16 weeks. Videographic analysis demonstrated the laser tissue welding repair trended toward superior outcomes compared with suture neurorrhaphy at all 4 time points. Electrophysiological analysis demonstrated similar or better results, with statistically significant improvement at week 16 (P laser nerve repair created a greater initial inflammatory reaction. An analysis of operative time demonstrated significantly decreased time and ease of use for laser tissue welding. This pilot study demonstrates that laser nerve welding may be an expedient, feasible, and safe method for facial nerve repair in a rabbit model. Further experiments with larger numbers are needed to provide additional evidence that laser tissue welding produces a neurorrhaphy that has functional, electrophysiological, and histological results that could rival traditional suture neurorrhaphy.

  7. ALTERATIONS IN TOTAL PROTEIN CONCENTRATION, SERUM PROTEIN FRACTIONS AND ALBUMIN/GLOBULIN RATIO IN HEALTHY RABBITS

    Directory of Open Access Journals (Sweden)

    Nuzhat Sultana

    2013-08-01

    Full Text Available This study assessed the effect of oral administration of Aloe vera and was to evaluate total serum protein, albumin and globulin concentrations as well as albumin / globulin (A / G ratio. Twenty rabbits weighing 1000 – 1800 g were divided into 2 groups. Each group consisted of ten animals. One served as control and other group served as experimental group. Results show that animals after 07, 15 and 30 days dosing of Aloe vera showed highly significant decrease in total protein and globulin and highly significant decrease in Albumin after 15 and 30 days of dosing of Aloe vera in comparison to control animals group. It is concluded that the long-term use of Aloe vera may cause hypoglobinemia and hypoalbuminemia at 30 days of dosing and it could be due to the liver diseases, evidence of hepatotoxicity induced Aloe vera also reported in previous studies.

  8. How does domain replacement affect fibril formation of the rabbit/human prion proteins.

    Directory of Open Access Journals (Sweden)

    Xu Yan

    Full Text Available It is known that in vivo human prion protein (PrP have the tendency to form fibril deposits and are associated with infectious fatal prion diseases, while the rabbit PrP does not readily form fibrils and is unlikely to cause prion diseases. Although we have previously demonstrated that amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and macromolecular crowding has different effects on fibril formation of the rabbit/human PrPs, we do not know which domains of PrPs cause such differences. In this study, we have constructed two PrP chimeras, rabbit chimera and human chimera, and investigated how domain replacement affects fibril formation of the rabbit/human PrPs.As revealed by thioflavin T binding assays and Sarkosyl-soluble SDS-PAGE, the presence of a strong crowding agent dramatically promotes fibril formation of both chimeras. As evidenced by circular dichroism, Fourier transform infrared spectroscopy, and proteinase K digestion assays, amyloid fibrils formed by human chimera have secondary structures and proteinase K-resistant features similar to those formed by the human PrP. However, amyloid fibrils formed by rabbit chimera have proteinase K-resistant features and secondary structures in crowded physiological environments different from those formed by the rabbit PrP, and secondary structures in dilute solutions similar to the rabbit PrP. The results from transmission electron microscopy show that macromolecular crowding caused human chimera but not rabbit chimera to form short fibrils and non-fibrillar particles.We demonstrate for the first time that the domains beyond PrP-H2H3 (β-strand 1, α-helix 1, and β-strand 2 have a remarkable effect on fibrillization of the rabbit PrP but almost no effect on the human PrP. Our findings can help to explain why amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and why macromolecular crowding has different

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

    Science.gov (United States)

    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.

  10. Recovery in ERG gene expression with biventricular pacing in a rabbit model of myocardial infarction

    Directory of Open Access Journals (Sweden)

    Saba S

    2013-05-01

    Full Text Available Samir Saba,* Haider Mehdi,* William Barrington, Fardeen Mehdi, Zahid Islam, Barry LondonCardiovascular Institute of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA*These authors contributed equally to this workBackground: Improved clinical and echocardiographic parameters have been documented with biventricular (BIV pacing in patients after myocardial infarction (MI. We investigated the changes in gene expression in cardiac tissue with BIV pacing, using a rabbit model of MI.Method: New Zealand White rabbits were divided into four groups: sham-operated controls, MI with no pacing, MI with right ventricle (RV pacing (MI + RV, and MI with BIV pacing (MI + BIV. Pacing was initiated 1–2 weeks after the coronary ligation. At 5 weeks, the hearts were excised. The tissue extracted from the left ventricle (LV and RV underwent analysis for protein and messenger ribonucleic acid (mRNA levels.Results: The ether-a-go-go-related gene (ERG protein levels recovered from the base of the LV away from the MI area were two- to threefold lower in the MI and the MI + RV compared with the MI + BIV groups (P = 0.07. The ERG protein levels were similar between the MI + BIV and the control groups. However, the RNA levels were comparable between the four study groups, suggesting that a posttranscriptional mechanism accounted for the difference in protein levels.Conclusion: In this rabbit model of MI, we demonstrated a recovery in ERG protein levels with BIV pacing, after MI. This recovery may underlie some of the benefits seen with BIV pacing in ischemic cardiomyopathy.Keywords: heart failure, biventricular pacing, cardiac reverse remodeling, ether-a-go-go-related gene

  11. Determining the critical size of a rabbit rib segmental bone defect model.

    Science.gov (United States)

    Liu, Fengzhen; Chen, Kun; Hou, Lei; Li, Keyi; Wang, Dawei; Zhang, Bin; Wang, Xiumei

    2016-10-01

    In order to establish and standardize the rabbit rib segmental bone defect model, it is of vital importance to determine rabbit rib critical size defect (CSD). According to the general time needed for spontaneous long-bone regeneration, three-month observation period was set to determine the CSD. The rabbit rib segmental bone defects with different sizes from 1 to 5 cm with or without periosteum were performed in the eighth rib of 4-month-old male New Zealand rabbits and underwent X-ray examinations at the 4th, 8th and 12th weeks postoperatively. The gross and histological examinations at postoperative week 12 were evaluated, which showed that the critical sizes in the rabbit rib models with and without periosteum were 5 and 2 cm, respectively. This study provides prerequisite data for establishing rabbit rib CSD model and evaluating bone materials using this model.

  12. Effect of losartan on sarcoplasmic reticulum Ca2+ handing proteins in heart failure rabbit

    Institute of Scientific and Technical Information of China (English)

    姚艳

    2006-01-01

    Objective To investigate the effects of losartan on mRNA expression of myocardial sarcoplasmic reticulum calcium handling proteins (SERCA2, RyR2 and PLB) and the role of which in prevention of chronic heart failure in rabbit. Methods After chronic heart failure was

  13. Age-related loss of calcium binding proteins in rabbit hippocampus

    NARCIS (Netherlands)

    deJong, GI; Naber, PA; VanderZee, EA; Thompson, LT; Disterhoft, JF; Luiten, PGM

    1996-01-01

    Using immunocytochemistry hippocampal levels of the calcium binding proteins calbindin 28K (CB) and parvalbumin (PV) was studied in young (1 month) to very old (60 month) Albino rabbits. Young (3 month) and senescent (30 month) Wistar rats were also examined to compare the distribution and age depen

  14. Studying the expression patterns of OCT4 and SOX2 proteins in regenerating rabbit ear tissue

    Directory of Open Access Journals (Sweden)

    A. S. Javanmard

    2016-06-01

    Full Text Available Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound healing in which blastema formation is involved in replacement of injured tissues. It has been suggested that isolated cells from regenerating rabbit ear possess stem-like properties. In this study, we aimed to determine the expression of stemness markers, OCT4 and SOX2 proteins, in regenerating rabbit tissues by immunohistochemistry. Results indicated that both proteins could be detected in epithelial cells, hair follicle cells and perichondrium cells. Expression pattern analysis of OCT4 and SOX2 proteins showed no clear differences between regenerative and non-regenerative control tissues. According to several reports of OCT4 and SOX2 proteins expression in adult stem cells, it could be proposed that OCT4 and SOX2 expressing cells in regenerating rabbit ear tissues are progenitor/adult stem cells which are resident in these tissues, and other markers should be used for detection of blastema cells.

  15. Age-related loss of calcium binding proteins in rabbit hippocampus

    OpenAIRE

    deJong, GI; Naber, PA; VANDERZEE, EA; Thompson, LT; Disterhoft, JF; Luiten, PGM

    1996-01-01

    Using immunocytochemistry hippocampal levels of the calcium binding proteins calbindin 28K (CB) and parvalbumin (PV) was studied in young (1 month) to very old (60 month) Albino rabbits. Young (3 month) and senescent (30 month) Wistar rats were also examined to compare the distribution and age dependency of PV and CB in both species. The distribution of PV-ir is similar in the rabbit and rat hippocampus. Aging in both species yielded a small loss of PV-ir in axon terminals. The presence of CB...

  16. Molecular evidence and functional expression of multidrug resistance associated protein (MRP) in rabbit corneal epithelial cells.

    Science.gov (United States)

    Karla, Pradeep K; Pal, Dananjay; Mitra, Ashim K

    2007-01-01

    Multidrug resistance associated protein (MRP) is a major family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify if the role of efflux transporters. MRP-2 is a major homologue of MRP family and found to express on the apical side of cell membrane. Cultured Rabbit Corneal Epithelial Cells (rCEC) were selected as an in vitro model for corneal epithelium. [14C]-erythromycin which is a proven substrate for MRP-2 was selected as a model drug for functional expression studies. MK-571, a known specific and potent inhibitor for MRP-2 was added to inhibit MRP mediated efflux. Membrane fraction of rCEC was used for western blot analysis. Polarized transport of [14C]-erythromycin was observed in rCEC and transport from B-->A was significantly high than from A-->B. Permeability's increased significantly from A-->B in the presence of MK-571 and ketoconozole. Uptake of [14C]-erythromycin in the presence of MK-571 was significantly higher than control in rCEC. RT-PCR analysis indicated a unique and distinct band at approximately 498 bp corresponding to MRP-2 in rCEC and MDCK11-MRP-2 cells. Immunoprecipitation followed by Western Blot analysis indicated a specific band at approximately 190 kDa in membrane fraction of rCEC and MDCK11-MRP-2 cells. For the first time we have demonstrated high expression of MRP-2 in rabbit corneal epithelium and its functional activity causing drug efflux. RT-PCR, immunoprecipitation followed by Western blot analysis further confirms the result.

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

    Science.gov (United States)

    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.

  18. Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

    Directory of Open Access Journals (Sweden)

    Leo Heyndrickx

    Full Text Available BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01. Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. RESULTS: It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model

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

    Directory of Open Access Journals (Sweden)

    Elizabeth W. Tucker

    2016-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  1. Endostatin inhibits hypertrophic scarring in a rabbit ear model

    Institute of Scientific and Technical Information of China (English)

    Hai-tao REN; Hang HU; Yuan LI; Hong-fei JIANG; Xin-lei HU; Chun-mao HAN

    2013-01-01

    Objective:The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation.Methods:Eight male New Zealand white rabbits were randomly assigned to two groups.Scar model was established by making six full skin defect wounds in each ear.For the intervention group,intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding).For the control group,equal volume of saline was injected.Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15,21,28,and 35 post wounding.Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding.Results:Macroscopically,scars of the control group were thicker than those of the intervention group.Significant differences between the two groups were observed on Days 21 and 35 (p<0.05).Scar thickness,measured by scar elevation index (SEI) at Day 35 post wounding,was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28).Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78)on Day 35.The distribution of collagen fibers in scars treated with endostatin was relatively regular,while collagen fibers in untreated controls were thicker and showed disordered alignment.Western blot analysis showed that the expressions of type Ⅰ collagen and Bcl-2 were depressed by injection of endostatin.Conclusions:Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation,possibly through reducing scar vascularization and angiogenesis.Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their

  2. Computational Studies of the Structural Stability of Rabbit Prion Protein Compared to Human and Mouse Prion Proteins

    CERN Document Server

    Zhang, Jiapu

    2011-01-01

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. The neurodegenerative diseases such as Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob diseases, Gerstmann-Str$\\ddot{a}$ussler-Scheinker syndrome, Fatal Familial Insomnia, Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow' disease) and chronic wasting disease in cattle belong to prion diseases. By now there have not been some effective therapeutic approaches to treat all these prion diseases. Dogs, rabbits and horses were reported to be resistant to prion diseases. By the end of year 2010 all the NMR structures of dog, rabbit and horse prion proteins (X-ray for rabbits too) had been finished to release into protein data bank. Thus, at this moment it is very worth studying the NMR and X-ray molecular structures of horse, dog and rabbit prion proteins to obtain insights into their immunity prion diseases. The author found that dog and horse prion proteins have sta...

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

    Science.gov (United States)

    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.

  4. Hemocoagulase atrox reduces vascular modeling in rabbit carotid artery adventitia

    Science.gov (United States)

    Wan, Sheng-Yun; Hu, Yuan-Cheng; Zhan, Yan-Qing; Qin, Dan-Dan; Ding, Yang

    2013-01-01

    Objective: This study aimed to compare the effects of hemocoagulase atrox and cauterization hemostasis on intimal hyperplasia and explore the effect of hemocoagulase atrox on vascular modeling in rabbit carotid artery adventitia. Methods: A total of 27 rabbits were randomly divided into 3 groups (0d, 14d, 28d). They were anaesthetized using an intramuscular injection of phenobarbital sodium (1 ml/kg). The left and right common carotid arteries were exposed and capillary hemorrhaged after blunt dissection of the adventitia layers of common carotid arteries. Nine rabbits in each group were again randomly divided into 3 groups, in which animals were respectively treated with hemocoagulase (2 U/ml), cauterization (power = 40 w) and saline (as control). Groups of animals were euthanized at 0, 14 and 28 days after surgery. The samples were equally divided in the middle of the adventitia removal section to obtain equal parts for histologic, immunohistochemical and molecular biologic analysis. The vascular repair after adventitial stripping was observed by HE staining, Masson staining and transmission electron microscopy. The expression of carotid MCP-1, PCNA, TGF-β1, α-SMA and VEGF were measured at different time points by RT-PCR and immunohistochemical staining. Results: HE staining and Masson staining showed that hemocoagulase atrox had a significantly stronger effect on reducing intimal hyperplasia than the cauterization after 14 and 28 days. The results of RT-PCR showed that the expression of MCP-1, TGF-β1, α-SMA and VEGF in hemocoagulase atrox-treated animals were lower than that of cauterization-treated animals. Conclusion: Our results suggested that hemocoagulase atrox as a topical hemostatic is safety and efficiently and it can accelerate adventitia restoration and decrease intimal proliferation. PMID:24228100

  5. Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model

    OpenAIRE

    Kesavan, Anup K.; Brooks, Megan; Tufariello, JoAnn; Chan, John; Manabe, Yukari C.

    2008-01-01

    As previously published, after aerosol infection with Mycobacterium tuberculosis H37Rv, New Zealand white rabbits established infection with active bacillary replication, but later contained disease to a paucibacillary state through an effective adaptive response consistent with latency. Despite the heterogeneity among outbred rabbits, the resistant response was uniform. Immunosuppression resulted in reactivation with increased lung bacillary burden. Using this rabbit model, we isolated bacil...

  6. Evaluation of Arterial Impairment after Experimental Gelatin Sponge Embolization in a Rabbit Renal Model

    OpenAIRE

    Oh, Jung Suk; Lee, Hae Giu; Chun, Ho Jong; Choi, Byung Gil; Choi, Yeong Jin

    2015-01-01

    Objective Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. Materials and Methods A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were perfor...

  7. The rabbit pup, a natural model of nursing anticipatory activity

    OpenAIRE

    Caba, Mario; González-Mariscal, Gabriela

    2009-01-01

    Mother rabbits nurse their young once a day with circadian periodicity. Nursing bouts are brief (ca. 3 min) and occur inside the maternal burrow. Despite this limited contact mother rabbits and their pups are tuned to each other to ensure that the capacities of each party are used efficiently to ensure the weaning of a healthy litter. In this review we present behavioral, hormonal, metabolic and hormonal correlates of this phenomenon in mother rabbits and their pups. Research is revealing tha...

  8. The rabbit as an animal model for post-natal vitreous matrix differentiation and degeneration

    NARCIS (Netherlands)

    Los, L. I.

    2008-01-01

    Purpose This study evaluates whether rabbits are a suitable animal model to study post-natal vitreous differentiation and degeneration. Methods Human and rabbit eyes of various ages were studied by complementary anatomical techniques, light microscopy, and transmission electron microscopy. Results T

  9. A rabbit model of graded primary mechanical injury to brainstem

    Institute of Scientific and Technical Information of China (English)

    YU Yong-min; WANG Xiao-wei; XUE Hai-bin; XIA Peng; LI Hong-wei; DAI Guo-xin; JI Xiao-yuan; ZHAO Hui; YIN Zhi-yong

    2012-01-01

    Objective:To introduce a new animal model of graded mechanical primary brainstem injury (BSI).Methods:Altogether 45 rabbits were subjected to BSI by type Ⅱ biological impact machine designed by the Third Military Medical University.The animals were divided into 4 experimental groups (n=10) and 1 control group (n=5) according to different magnitudes of impact pressure imposed on the occipital nodule:Group 1,500-520 kPa; Group 2,520-540 kPa; Group 3,540-560 kPa; Group 4,560-580 kPa and Group 5,0 kPa with 20 kPa increase in each grade.The impact depth was a constant 0.5 cm.After injury,the clinical symptoms and signs as well as pathological changes were observed.Results:Rabbits in Group 1 revealed mild physiological reaction of BSI.They had localized cerebral contusion with punctate hemorrhage and subarachnoid hemorrhage (SAH) was limited to the peripheral tissues at the impact area.In Group 2,obvious physiological reaction was observed.Local pathological lesions reached the superficial layer ofbrainstem tissues; focal hemorrhage and girdleshaped SAH in basilar pon were observed under microscope.In Group 3,BSI was more severe with a long respiratory depression.Pathological lesions reached the inner portion of brainstem with massive hemorrhage and the whole brainstem was wrapped by subarachnoid hematoma.In Group 4,most rabbits died due to severe BSI.Pathological lesions deepened to the central brainstem with wide pathological change,rapture of the medulla oblongata central canal.Group 5 was the control group,with normal brainstem structure and no lesion observed.Conclusion:This model successfully simulates different levels ofbrainstem mechanical injury and clearly shows the subsequent pathological changes following injury.It takes two external parameters (impact pressure and depth) and has a similar injury mechanism to clinical accelerating BSI.Moreover it is reproducible and stable,thus being beneficial for exploring pathophysiological mechanism,diagnosis and

  10. Effect of feed restriction and different crude protein sources on the performance, health status and carcass traits of growing rabbits

    Directory of Open Access Journals (Sweden)

    L. Uhlířová

    2015-12-01

    Full Text Available We evaluate the effect of the crude protein source (CP in combination with 2 feeding strategies (AL: ad libitum or R: restricted on the performance, health status and carcass traits of growing-fattening rabbits (between 33 and 75 d of age. Two experimental diets were formulated; the first containing soybean meal (SBM: 70 g/kg as the main CP source and the second containing white lupin seeds (WLS: 105 g/kg as the main CP source. A total of 160 weaned Hyplus rabbits (774±10 g live weight were randomly allocated to the experimental groups, combination of feeding strategy and diet (AL SBM, R SBM, AL WLS and R WLS; 40 rabbits per group with 4 rabbits per cage, for 42 d. The feeding programme was applied as follows: both the AL SBM and AL WLS rabbits were fed ad libitum for the entire fattening period, whereas the R SBM and R WLS rabbits were subjected to feed restriction between 33 and 47 d of age (75% of the ad libitum intake. Afterwards, all restricted rabbits were fed ad libitum until 75 d of age. Regardless of the CP source, the feed restriction reduced the final live weight by 83 g, chilled carcass weight by 65 g, and dressing out percentage by 0.9 percentage points (P<0.05. There was a higher chilled carcass weight (+114 g; P=0.001 and reference carcass weight (+91 g; P=0.001 in rabbits fed with WLS diet than in rabbits fed with SBM diet. No dead or morbid rabbits were observed in restricted rabbits during the restriction period. There was no effect of the diet on the health of rabbits. However when the rabbits of AL SBM and AL WLS group were compared did we observe a lower number of rabbits at sanitary risk in AL WLS group (2 vs. 12 rabbits, P=0.006. In conclusion, the growth performance was not affected by the crude protein source, and no interaction between dietary CP source and feeding regime was observed. Feed restriction regime did not improve sanitary risk index throughout the entire period.

  11. Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

    Science.gov (United States)

    Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

    2011-02-01

    Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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

    Science.gov (United States)

    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.

  13. Effects of estradiol on reduction of osteoarthritis in rabbits through effect on matrix metalloproteinase proteins

    Directory of Open Access Journals (Sweden)

    Weiguo Wang

    2016-03-01

    Full Text Available Objective(s: Osteoarthritis (OA, as a known degenerative joint disease, is the most common form of arthritis. In this study, we aimed to elucidate unclear pathogenesis of OA. Materials and Methods: Rabbit models of OA were established by the transection of the anterior cruciate ligament. Rabbits were randomly divided into three equal groups: the experimental group (OA modeling, treated with estradiol, the control group (OA modeling, treated with normal saline and the normal group (without OA modeling. The glycosaminoglycan (GAG and hyaluronan (HA content of knee joint were collected and assayed. In addition, gene expression of matrix metalloproteinase (MMP-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP-1 were evaluated by real-time PCR and Western blot analysis. Results: Animal models were developed successfully. GAG and HA concentrations were significantly increased in the experimental and the normal group compared with the control group (PP

  14. Characterization and localization of the rabbit ocular calcitonin gene-related peptide (CGRP)-receptor component protein (RCP).

    Science.gov (United States)

    Rosenblatt, M I; Dahl, G P; Dickerson, I M

    2000-04-01

    To determine whether the calcitonin gene-related peptide (CGRP) receptor component protein (RCP), a novel signal transduction molecule, is required for CGRP signaling in the eye and to determine potential ocular sites of CGRP action. The cDNA for the rabbit ocular RCP homologue was cloned using a combination of reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). Function of the rabbit ocular RCP was assessed using a sensitive oocyte-based assay, which utilizes the protein kinase A (PKA)-sensitive cystic fibrosis transmembrane conductance regulator (CFTR) as a sensor of cAMP formation. RCP expression in the rabbit eye was localized using immunohistochemistry. A 2063-bp cDNA for the rabbit ocular RCP was cloned and sequenced. Expression of the rabbit RCP cDNA confers CGRP responsiveness in a sensitive oocyte-based assay. Antisense oligonucleotides made to the ocular RCP abolishes CGRP responsiveness of ciliary body and iris mRNA in the oocyte-CFTR assay. Localization of RCP protein in the rabbit eye using immunohistochemistry demonstrated RCP immunoreactivity in the ciliary body and iris blood vessels, as well as in layers of the ciliary epithelium. The rabbit ocular RCP appears to be required for signal transduction at ocular CGRP receptors and is localized to sites previously reported to bind CGRP, which affect intraocular pressure and neurogenic inflammation.

  15. Twenty years of experience with the rabbit model, a versatile model for tracheal transplantation research

    Institute of Scientific and Technical Information of China (English)

    Margot Den Hondt; Bart M Vanaudenaerde; Pierre Delaere; Jan J Vranckx

    2016-01-01

    Pathologies comprising more than half the length of the trachea are a challenge to the reconstructive surgeon. Innovative tracheal transplantation techniques aim to offer the patient a curative solution with a sustained improvement in quality of life. This review summarizes the authors’ experience with the rabbit as a versatile model for research regarding tracheal transplantation. Because of the segmental blood supply of the trachea, it is not feasible to transplant the organ together with a well-defined vascular pedicle. As such, the key element of successful tracheal transplantation is the creation of a new blood supply. This vascularized construct is created by prelaminating the rabbit trachea heterotopically, within the lateral thoracic fascia. After prelamination, the construct and its vascular pedicle are transferred to the orthotopic position in the neck. This model has become gold standard because of the advantages of working with rabbits, the anatomy of the rabbit trachea, and the reliability of the lateral thoracic artery flap. In this paper, the key elements of surgery in the rabbit are discussed, as well as the tracheal anastomosis and the harvest of the lateral thoracic artery flap. Practical tips and tricks are presented. The data described in this review represent the fundaments of ongoing translational research in the center over the past twenty years.

  16. Research on Perfusion CT in Rabbit Brain Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Bon Chul; Kwak, Byung Kook; Jung, Ji Sung [Dept. of Diagnostic Radiology, Chung Ang University Hospital, Seoul (Korea, Republic of); Lim, Cheong Hwan; Jung, Hong Ryang [Dept. of Radiological Science, Hanseo University, Seosan (Korea, Republic of)

    2012-06-15

    We investigated the vascular characteristics of tumors and normal tissue using perfusion CT in the rabbit brain tumor model. The VX2 carcinoma concentration of 1 x 10{sup 7} cells/ml(0.1 ml) was implanted in the brain of nine New Zealand white rabbits (weight: 2.4 kg-3.0 kg, mean: 2.6 kg). The perfusion CT was scanned when the tumors were grown up to 5 mm. The tumor volume and perfusion value were quantitatively analyzed by using commercial workstation (advantage windows workstation, AW, version 4.2, GE, USA). The mean volume of implanted tumors was 316{+-}181 mm{sup 3}, and the biggest and smallest volumes of tumor were 497 mm{sup 3} and 195 mm{sup 3}, respectively. All the implanted tumors in rabbits are single-nodular tumors, and intracranial metastasis was not observed. In the perfusion CT, cerebral blood volume (CBV) were 74.40{+-}9.63, 16.8{+-}0.64, 15.24{+-}3.23 ml/100g in the tumor core, ipsilateral normal brain, and contralateral normal brain, respectively (p{<=}0.05). In the cerebral blood flow (CBF), there were significant differences between the tumor core and both normal brains (p{<=}0.05), but no significant differences between ipsilateral and contralateral normal brains (962.91{+-}75.96 vs. 357.82{+-}12.82 vs. 323.19{+-}83.24 ml/100g/min). In the mean transit time (MTT), there were significant differences between the tumor core and both normal brains (p{<=}0.05), but no significant differences between ipsilateral and contralateral normal brains (4.37{+-}0.19 vs. 3.02{+-}0.41 vs. 2.86{+-}0.22 sec). In the permeability surface (PS), there were significant differences among the tumor core, ipsilateral and contralateral normal brains (47.23{+-}25.44 vs. 14.54{+-}1.60 vs. 6.81{+-}4.20 ml/100g/min)(p{<=}0.05). In the time to peak (TTP) were no significant differences among the tumor core, ipsilateral and contralateral normal brains. In the positive enhancement integral (PEI), there were significant differences among the tumor core, ipsilateral and

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

    Directory of Open Access Journals (Sweden)

    Jennyffer Cruz

    Full Text Available 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

  18. Early Ankle Mobilization Promotes Healing in a Rabbit Model of Achilles Tendon Rupture.

    Science.gov (United States)

    Jielile, Jiasharete; Asilehan, Batiza; Wupuer, Aikeremu; Qianman, Bayixiati; Jialihasi, Ayidaer; Tangkejie, Wulanbai; Maimaitiaili, Abudouheilil; Shawutali, Nuerai; Badelhan, Aynaz; Niyazebieke, Hadelebieke; Aizezi, Adili; Aisaiding, Amuding; Bakyt, Yerzat; Aibek, Rakimbaiev; Wuerliebieke, Jianati

    2016-01-01

    The use of early mobilization of the ankle joint without orthosis in the treatment of Achilles tendon rupture has been advocated as the optimal management. The goal of this study was to compare outcomes in a postoperative rabbit model of Achilles tendon rupture between early mobilization and immobilized animals using a differential proteomics approach. In total, 135 rabbits were randomized into the control group (n=15), the postoperative cast immobilization (PCI) group (n=60), and the early mobilization (EM) group (n=60). A rupture of the Achilles tendon was created in each animal model and repaired microsurgically, and tendon samples were removed at 3, 7, 14, and 21 days postoperatively. Proteins were separated using 2-dimensional polyacrylamide gel electrophoresis and identified using peptide mass fingerprinting, tandem mass spectrometry, NCBI database searches, and bioinformatics analyses. A series of differentially expressed proteins were identified between groups, some of which may play an important role in Achilles tendon healing. Notable candidate proteins that were upregulated in the EM group were identified, such as CRMP-2, galactokinase 1, tropomyosin-4, and transthyretin. The healing of ruptured Achilles tendons appears to be affected at the level of protein expression with the use of early mobilization. The classic postoperative treatment of Achilles tendon rupture with an orthosis ignored the self-protecting instinct of humans. With a novel operative technique, the repaired tendon can persist the load that comes from traction in knee and ankle joint functional movement. In addition, kinesitherapy provided an excellent experimental outcome via a mechanobiological mechanism. Copyright 2016, SLACK Incorporated.

  19. Digestible fibre to starch ratio and protein level in diets for growing rabbits

    Directory of Open Access Journals (Sweden)

    Gerolamo Xiccato

    2010-01-01

    Full Text Available To evaluate the effect of digestible fibre (DF to starch ratio (0.8, 1.5, and 2.8 and protein level (15% and 16% on health status, digestive physiology, growth performance, and carcass traits, 246 rabbits weaned at 33 d were fed until slaughter (75 d six diets formulated according to a bi-factorial arrangement (3 DF to starch ratios by 2 protein levels. Growth performance and carcass quality at slaughter were not af- fected by treatments. Increasing DF to starch ratio did not modify dry matter digestibility (62.0% on average, while increased (P<0.001 DF digestibility (52.3 to 68.1%, stimulated caecal fermentation (total VFA: 56.0 vs 67.8 and 67.2 mmol/l; P=0.02 and changed VFA molar proportions. Increasing dietary protein increased digestibility of dry matter (P=0.02, crude protein (P<0.001 and digestible fibre (P<0.001 and increased cae- cal VFA production (P<0.01. The highest mortality (17.1% vs 1.5% average mortality of the other groups, P<0.001 was found in rabbits fed the diet with the lowest DF to starch ratio and the highest protein level.

  20. Implementation of the ISTH classification of non-overt DIC in a thromboplastin induced rabbit model

    DEFF Research Database (Denmark)

    Berthelsen, Line Olrik; Kristensen, Annemarie Thuri; Wiinberg, Bo

    2009-01-01

    , but the scoring systems have rarely been applied to animal models of DIC. In this study, we use rabbit brain thromboplastin (thromboplastin) to induce DIC in a rabbit model and test the applicability of the ISTH criteria for standardized diagnosis of DIC. Cardiovascular and haematological parameters from rabbits...... thromboplastin/kg was lethal. For the remaining groups, a dose dependent decrease in blood pressure, platelet count and fibrinogen level together with a dose dependent increase in prothrombin time, activated partial thromboplastin time, level of thrombin-antithrombin complexes, fibrin degradation products...

  1. Modelling the chronotropic effect of isoprenaline on rabbit sinoatrial node

    Directory of Open Access Journals (Sweden)

    Henggui eZhang

    2012-07-01

    Full Text Available Introduction: β-adrenergic stimulation increases the heart rate by accelerating the electrical activity of the pacemaker of the heart, the sinoatrial node (SAN. Ionic mechanisms underlying the actions of β-adrenergic stimulation are not yet fully understood. Isoprenaline (ISO, a β-adrenoceptor agonist, shifts voltage-dependent If activation to more positive potentials resulting in an increase of If, which has been suggested to be the main mechanism underlying the effect of β-adrenergic stimulation. However, ISO has been found to increase the firing rate of rabbit SAN cells when If is blocked. ISO also increases ICaL, Ist, IKr and IKs; and shifts the activation of IKr to more negative potentials and increases the rate of its deactivation. ISO has also been reported to increase the intracellular Ca2+ transient, which can contribute to chronotropy by modulating the Ca2+ clock. The aim of this study was to analyse the ionic mechanisms underlying the positive chronotropy of β-adrenergic stimulation using two distinct and well established computational models. Methods and results: We modified the Boyett et al. (2001 and Kurata et al. (2008 models of electrical activity for the central and peripheral rabbit SAN cells by incorporating equations for the known dose-dependent actions of ISO on various ionic channel currents (ICaL, Ist, IKr and IKs, kinetics of IKr and If, and the intracellular Ca2+ transient. These equations were constructed from experimental data. To investigate the ionic basis of the effects of ISO, we simulated the chronotropic effect of a range of ISO concentrations when ISO exerted all its actions or just a subset of them. Conclusions: In both the Boyett et al. and Kurata et al. SAN models, the chronotropic effect of ISO was found to result from an integrated action of ISO on ICaL, If, Ist, IKr and IKs, among which an increase in the rate of deactivation of IKr plays a prominent role, though the effect of ISO on If and [Ca]i also

  2. NIRS PREDICTION FOR PROTEIN AND INTRAMUSCULAR FAT CONTENT OF RABBIT HIND LEG MEAT

    Directory of Open Access Journals (Sweden)

    Gy. Bázár

    2007-06-01

    Full Text Available The goal of this study was to develop calibration equations to predict the chemical composition of raw, homogenized rabbit meat by means of near infrared spectroscopy (NIRS. 44 Pannon White rabbits were housed in groups in three different pen types (16 anim./m2, and were fed the same diet. Another 45 animals were housed in cages (12 anim./m2 and fed by different feeding regimes. Rabbits were slaughtered at the bodyweight of 2.4-2.5 kg. Homogenized fresh and freeze-dried left total hind leg muscles were investigated by NIRS using a NIRSystem 6500 equipment with small ring cup sample holder. The ether extract and protein content of all samples were determined chemically. Samples 44 of housing experiment were applied in producing LOCAL calibration equations tested on the 45 samples from the separate feeding experiment. Coefficients of determination (R2 of the predictions were 0.89 and 0.99 for fat, 0.85 and 0.96 for protein in fresh and freeze-dried samples, respectively. Results are reassuring, because the equations were applicable, however the analyzed samples were from independent housing and feeding systems. Therefore the chemical compositions differed in the two datasets, i.e. 9.46%, and 11.79% for fat, 85.75% and 83.44% for protein content in calibration and prediction datasets, respectively. The average of NIRS predicted values for fat and protein was 11.36%, 83.88% or 11.54%, 83.45% when using fresh or freeze-dried samples, respectively.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Osteitis and mucosal inflammation in a rabbit model of sinusitis.

    Science.gov (United States)

    Campos, Carlos Augusto Correia de; Dolci, Eduardo Landini Lutaif; Silva, Leonardo da; Dolci, José Eduardo Lutaif; Campos, Carlos Alberto Herrerias de; Dolci, Ricardo Landini Lutaif

    2015-01-01

    Several experimental studies have shown osteitis after the onset of sinusitis, supporting the idea that bone involvement could participate in the dissemination and perpetuation of this inflammatory disease. However, procedures commonly performed for the induction of sinusitis, such as antrostomies, can trigger sinusitis by themselves. To evaluate osteitis in an animal model of sinusitis that does not violate the sinus directly and verify whether this is limited to the induction side, or if it affects the contralateral side. Experimental study in which sinusitis was produced by inserting an obstructing sponge into the nasal cavity of 20 rabbits. After defined intervals, the animals were euthanized and maxillary sinus samples were removed for semi-quantitative histological analysis of mucosa and bone. Signs of bone and mucosal inflammation were observed, affecting both the induction and contralateral sides. Statistical analysis showed correlation between the intensity of osteitis on both sides, but not between mucosal and bone inflammation on the same side, supporting the theory that inflammation can spread through bone structures, regardless of mucosal inflammation. This study demonstrated that in an animal model of sinusitis that does not disturb the sinus directly osteitis occurs in the affected sinus and that it also affects the contralateral side. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

    Science.gov (United States)

    2012-06-13

    daily low-dose Bacillus anthracis spore inhalation exposures in the rabbit model Roy E. Barnewall 1, Jason E. Comer 1, Brian D. Miller 1, BradfordW...multiple exposure days. Keywords: Bacillus anthracis , inhalation exposures, low-dose, subchronic exposures, spores, anthrax, aerosol system INTRODUCTION... Bacillus Anthracis Spore Inhalation Exposures In The Rabbit Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

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

    Science.gov (United States)

    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.

  7. Adopting oculopressure tonometry as a transient in vivo rabbit glaucoma model

    Directory of Open Access Journals (Sweden)

    Stahnke T.

    2015-09-01

    Full Text Available Glaucoma represents a group of eye disorders partly related to raised intraocular pressure (IOP leading to progressive optic nerve damage resulting in impaired vision and possibly blindness. To assess the suitability of new IOP lowering therapeutic strategies, such as the implantation of glaucoma drainage devices, appropriate animal models have to be used. Currently, a number of rodent glaucoma models are available [1], however, especially for surgical interventions rodent eyes are too small. Rabbits are much more suitable with respect to dimension. Unfortunately, rabbit glaucoma model systems described in literature are difficult to reproduce or fail totally, associated with a high level of discomfort and pain for treated animals. Therefore, development of an in vivo rabbit glaucoma model is one of the most important goals in glaucoma research. Here, we describe the adaptation of the oculopressure tonometry, an existing method to quantify the outflow of aqueous humor in humans, to generate a transient glaucoma model in rabbits. The existing suction-cup oculopressor (SCOP is extended with newly designed suction-cups, which are adjusted to the anatomy of the rabbit eye. The modification of the oculopressure tonometry method facilitates an increase in IOP over a time frame of 9 minutes by vacuum induced deformation of the rabbit eye. This method can be used to test functionality of fistulating glaucoma surgeries or implanted drainage devices in a long term follow-up without any side effects and suffering of the animals.

  8. A model of myxomatosis based on hormonal control of rabbit-flea reproduction.

    Science.gov (United States)

    Antonelli, P L; Seymour, R M

    1988-01-01

    A two-dimensional first-order nonlinear system of ordinary differential equations with constant coefficients is constructed to model the rabbit/flea dynamics of the European rabbit viral disease known as myxomatosis. It is proved that infected fleas induce stable oscillations of small amplitude for a range of coefficient values when the Rothschild coupling coefficient r, which models biochemical control of flea reproduction by the rabbit, attains a critical (Hopf) value rO. These oscillations may lead to rapid local extinction of rabbits depending on the virulence gamma 2 of myxoma. The coefficient gamma 1 = r gamma 2 measures the effect on the fleas. Since the four determining coefficients may change over evolutionary time-scales, the mathematical results together with a natural selection argument proves that virulence gamma 2 attenuates. This has been observed both in Australia and in Great Britain. However, the rabbit flea Spilopsyllus cuniculi is not an effective vector for myxoma in Australia, but is the principal vector in Britain, as verified by R. Muirhead-Thomson at the suggestion of M. Rothschild. This preliminary model assumes density-independent rabbit reproductivity pR, but the qualitative results hold for a wider class of density-dependent models. Yet, the former condition is basic for the technique of parameter reduction used to simplify statistical estimation of the more general density-dependent model.

  9. SERUM PROTEIN CHANGES IN RABBITS AFTER CHRONIC ADMINISTRATION OF LEAD AND CADMIUM

    Directory of Open Access Journals (Sweden)

    Hristo HRISTEV

    2008-07-01

    Full Text Available The infl uence of lead (5mg/kg b.w and cadmium (2mg/kg b.w after chronic treatment of the rabbits on serum protein is investigated. Signifi cantly raised content of the cholesterol, ASAT and ALAT; hypo-albuminemia and hyperbetaglobulinemia of the background of one hypoproteinemia and low A/G coeffi cient are established. On basis of obtained result can to show degree of liver parenchyma damage and as trial for used the hyperbeta-globulinemia (at chronic treatment with cadmium is stronger markedly as indicator for delimitation of enteral from parenteral toxication, at that is noted hypergamma-globulinemia.

  10. Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

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    J.B. Rezende-Neto

    2010-12-01

    Full Text Available Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals and hypotensive resuscitation at 60% of baseline MAP (10 animals. Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg. Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%, sham (95 ± 2.8 vs 59 ± 4.1%, and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%. Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

  11. Effect of Momordica charantia (bitter melon on serum glucose level and various protein parameters in acetaminophen intoxicated rabbits

    Directory of Open Access Journals (Sweden)

    Kanwal Zahra

    2012-02-01

    Full Text Available Aim: Liver function tests, including total plasma proteins, albumin, bilirubin and glucose were analyzed to find out the hepatocurative and hepatoprotective effects of Momordica charantia. Method: The study was divided into two categories. In first category, the livers of rabbits were intoxicated with acetaminophen, and then Momordica fruit extract was given to observe its hepatocurative effects. Results: The results indicated significant changes in concentrations of the parameters in acetaminophen-challenged rabbits. In the second category, treatment was started by giving Momordica fruit extract dose orally for 10 days and 15 days to two groups of rabbits, respectively. Then, livers of rabbits were damaged with acetaminophen and hepatoprotective effects of Momordica were observed. Conclusion: The results showed that the animals treated with Momordica fruit extract experienced less liver damage due to acetaminophen intoxication, indicating that Momordica has hepatoprotective properties. [J Intercult Ethnopharmacol 2012; 1(1.000: 7-12

  12. Evaluation of the microcirculation in a rabbit hemorrhagic shock model using laser Doppler imaging.

    Science.gov (United States)

    Luo, Zhenchun; Wang, Pengfei; Zhang, An; Zuo, Guoqing; Zheng, Yuanyi; Huang, Yan

    2015-01-01

    The aim of this study is to evaluate the feasibility of Laser Doppler imaging (LDI) for noninvasive and dynamic assessment of hemorrhagic shock in a rabbit model. A rabbit model of hemorrhagic shock was generated and LDI of the microcirculation in the rabbit ears was performed before and at 0, 30, 60, and 90 min after hemorrhage. The CCD (Charge Coupled Device) image of the ears, the mean arterial pressure (MAP) and the heart rate (HR) were monitored. The mean LDI flux was calculated. The HR of rabbits was significantly (p 0.05). Both the flux numbers and the red-to-blue color changes on LDI imaging showed the reduction of the microcirculation. LDI imaging is a noninvasive and non-contact approach to evaluate the microcirculation and may offer benefits in the diagnosis and treatment of hemorrhage shock. Further studies are needed to confirm its effectiveness in clinical practice.

  13. Evaluation of the microcirculation in a rabbit hemorrhagic shock model using laser Doppler imaging.

    Directory of Open Access Journals (Sweden)

    Zhenchun Luo

    Full Text Available The aim of this study is to evaluate the feasibility of Laser Doppler imaging (LDI for noninvasive and dynamic assessment of hemorrhagic shock in a rabbit model. A rabbit model of hemorrhagic shock was generated and LDI of the microcirculation in the rabbit ears was performed before and at 0, 30, 60, and 90 min after hemorrhage. The CCD (Charge Coupled Device image of the ears, the mean arterial pressure (MAP and the heart rate (HR were monitored. The mean LDI flux was calculated. The HR of rabbits was significantly (p 0.05. Both the flux numbers and the red-to-blue color changes on LDI imaging showed the reduction of the microcirculation. LDI imaging is a noninvasive and non-contact approach to evaluate the microcirculation and may offer benefits in the diagnosis and treatment of hemorrhage shock. Further studies are needed to confirm its effectiveness in clinical practice.

  14. Immune Reactivity of Brucella Melitensis–Vaccinated Rabbit Serum with Recombinant Omp31 and Dnak Proteins

    Directory of Open Access Journals (Sweden)

    Mahmood Jeddi-Tehrani

    2013-03-01

    Full Text Available Background and objectives: Brucella melitensis infection is still a major health problem for human and cattle in developing countries and the Middle East.Materials and Methods: In this study, in order to screen immunogenic candidate antigens for the development of a Brucella subunit vaccine, a cytoplasmic protein (DnaK and an outer membrane protein (Omp31 of B. melitensis were cloned, expressed in E.coli BL21 and then purified using Ni-NTA agarose. Immunized serum was prepared from a rabbit inoculated with attenuated B. melitensis.Results and Conclusion: It was proved that immunized serum contains antibodies against recombinant Omp31 (rOmp31 and DnaK (rDnaK by Western blot and ELISA assays. The results may suggest the importance of these proteins as subunit vaccines against B. melitensis as well as targets for immunotherapy.

  15. Influence of human diets containing casein, soy protein isolate, and soy protein concentrate on serum cholesterol and lipoproteins in humans, rabbits and rats

    NARCIS (Netherlands)

    Raaij, van J.M.A.

    1982-01-01

    It is well known that feeding animals such as rabbits with semipurified diets containing animal proteins, as for example casein, results in hypercholesterolemia and atherosclerosis. On the other hand, diets containing vegetable proteins such as soybean protein maintain low levels of serum cholestero

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

    OpenAIRE

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

    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 ...

  17. Persistent Bacteremia in Rabbit Fetuses despite Maternal Antibiotic Therapy in a Novel Intrauterine-Infection Model

    OpenAIRE

    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.

    2003-01-01

    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, qua...

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

    Science.gov (United States)

    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

  19. Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV).

    Science.gov (United States)

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  20. Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

    Directory of Open Access Journals (Sweden)

    Jie Zhu

    Full Text Available Rabbit hemorrhagic disease virus (RHDV, the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  1. Self-assembly of virus-like particles of rabbit hemorrhagic disease virus capsid protein expressed in Escherichia coli and their immunogenicity in rabbits.

    Science.gov (United States)

    Guo, Huimin; Zhu, Jie; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Sun, Shiqi; Liu, Guangqing

    2016-07-01

    In this study, virus-like particles (VLPs) derived from rabbit hemorrhagic disease virus (RHDV) were evaluated for the development of a vaccine against RHDV infection. The VP60 gene was cloned and inserted into a pSMK expression vector containing a small ubiquitin-like modifier (SUMO) tag that can promote the soluble expression of heterologous proteins in Escherichia coli cells. After expression and purification of His-SUMO-VP60 and cleavage of the SUMO tag, we found that the RHDV VP60 protein had self-assembled into VLPs with a similar shape and smaller size compared with authentic RHDV capsid. Next, the antigenicity and immunogenicity of the VLPs were examined. The results showed that RHDV-specific responses were clearly induced in rabbits and that all rabbits in the VLP group survived while those in the negative control group died within 72 h post-infection. These results suggest that VLP-based RHDV could be a promising RHDV vaccine candidate.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model.

    Science.gov (United States)

    Kesavan, Anup K; Brooks, Megan; Tufariello, JoAnn; Chan, John; Manabe, Yukari C

    2009-01-01

    As previously published, after aerosol infection with Mycobacterium tuberculosis H37Rv, New Zealand white rabbits established infection with active bacillary replication, but later contained disease to a paucibacillary state through an effective adaptive response consistent with latency. Despite the heterogeneity among outbred rabbits, the resistant response was uniform. Immunosuppression resulted in reactivation with increased lung bacillary burden. Using this rabbit model, we isolated bacillary RNA from infected rabbit lungs and assessed transcriptional profiles of bacillary genes using RT-PCR to examine genes differentially regulated during active replication, persistence, steroid-induced reactivation, and post-steroid immune reconstitution. Genes involved in hypoxia response (fdxA), resuscitation promoting factors (rpfB), and DNA repair pathways (Rv2191) may be important in bacillary persistence. Further investigation into these gene pathways is warranted.

  5. Modeling complexes of modeled proteins.

    Science.gov (United States)

    Anishchenko, Ivan; Kundrotas, Petras J; Vakser, Ilya A

    2017-03-01

    Structural characterization of proteins is essential for understanding life processes at the molecular level. However, only a fraction of known proteins have experimentally determined structures. This fraction is even smaller for protein-protein complexes. Thus, structural modeling of protein-protein interactions (docking) primarily has to rely on modeled structures of the individual proteins, which typically are less accurate than the experimentally determined ones. Such "double" modeling is the Grand Challenge of structural reconstruction of the interactome. Yet it remains so far largely untested in a systematic way. We present a comprehensive validation of template-based and free docking on a set of 165 complexes, where each protein model has six levels of structural accuracy, from 1 to 6 Å C(α) RMSD. Many template-based docking predictions fall into acceptable quality category, according to the CAPRI criteria, even for highly inaccurate proteins (5-6 Å RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD > 4 Å. The results show that the existing docking methodologies can be successfully applied to protein models with a broad range of structural accuracy, and the template-based docking is much less sensitive to inaccuracies of protein models than the free docking. Proteins 2017; 85:470-478. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Protein Models Comparator

    CERN Document Server

    Widera, Paweł

    2011-01-01

    The process of comparison of computer generated protein structural models is an important element of protein structure prediction. It has many uses including model quality evaluation, selection of the final models from a large set of candidates or optimisation of parameters of energy functions used in template free modelling and refinement. Although many protein comparison methods are available online on numerous web servers, their ability to handle a large scale model comparison is often very limited. Most of the servers offer only a single pairwise structural comparison, and they usually do not provide a model-specific comparison with a fixed alignment between the models. To bridge the gap between the protein and model structure comparison we have developed the Protein Models Comparator (pm-cmp). To be able to deliver the scalability on demand and handle large comparison experiments the pm-cmp was implemented "in the cloud". Protein Models Comparator is a scalable web application for a fast distributed comp...

  7. Optimisation of reference genes for gene-expression analysis in a rabbit model of left ventricular diastolic dysfunction.

    Directory of Open Access Journals (Sweden)

    Walid Nachar

    Full Text Available Left ventricular diastolic dysfunction (LVDD is characterized by the disturbance of ventricle's performance due to its abnormal relaxation or to its increased stiffness during the diastolic phase. The molecular mechanisms underlying LVDD remain unknown. We aimed to identify normalization genes for accurate gene-expression analysis of LVDD using quantitative real-time PCR (RT-PCR in a new rabbit model of LVDD. Eighteen rabbits were fed with a normal diet (n = 7 or a 0.5% cholesterol-enriched diet supplemented with vitamin D2 (n = 11 for an average of 14.5 weeks. We validated the presence of LVDD in this model using echocardiography for diastolic function assessment. RT-PCR was performed using cDNA derived from left ventricle samples to measure the stability of 10 genes as candidate reference genes (Gapdh, Hprt1, Ppia, Sdha, Rpl5, Actb, Eef1e1, Ywhaz, Pgk1, and G6pd. Using geNorm analysis, we report that Sdha, Gapdh and Hprt1 genes had the highest stability (M <0.2. By contrast, Hprt1 and Rpl5 genes were found to represent the best combination for normalization when using the Normfinder algorithm (stability value of 0.042. Comparison of both normalization strategies highlighted an increase of natriuretic peptides (Bnp and Anp, monocytes chemotactic protein-1 (Mcp-1 and NADPH oxidase subunit (Nox-2 mRNA expressions in ventricle samples of the hypercholesterolemic rabbits compared to controls (P<0.05. This increase correlates with LVDD echocardiographic parameters and most importantly it molecularly validates the presence of the disease in our model. This is the first study emphasizing the selection of stable reference genes for RT-PCR normalization in a rabbit model of LVDD.

  8. Sequence and gene expression analysis of the agouti signalling protein gene in Rex rabbits with different coat colours

    Directory of Open Access Journals (Sweden)

    Cuijun Yang

    2015-08-01

    Full Text Available Rex rabbits have a unique fur structure with a variety of different coat colours. In this study, we analysed variability in the agouti signalling protein (ASIP gene in Rex rabbits with different coat colours (castor, red, blue, chinchilla, otter and black. Three alleles at this locus were identified: A, light-bellied agouti (wild type, in castor and chinchilla Rex; at, black and tan, in otter, castor and chinchilla Rex; and a, black non-agouti, in black, red, blue, castor and chinchilla Rex rabbits. Two missense mutations, two synonymous substitutions and one indel were the identified polymorphisms associated to these three alleles, as already described by others. Gene expression of the ASIP gene was also evaluated in different tissues from animals of the six coat colours. Agouti signalling protein expression was always observed in all tissue/coat colour combinations.

  9. Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model

    DEFF Research Database (Denmark)

    Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne Bendixen

    2013-01-01

    Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence...

  10. Landscape ecology and wild rabbit (Oryctolagus cuniculus habitat modeling in the Mediterranean region

    Directory of Open Access Journals (Sweden)

    Narce, M.

    2012-01-01

    Full Text Available Landscape modification is one of the reasons for the decrease in rabbit populations. The objective of this study was to model wild rabbit habitat using landscape ecology to create a diagnosis method able to assess habitat quality at a large scale. Rabbit presence/absence was recorded on 536 plots of 1 ha. Spotlight transect counts indicated a low relative abundance (KIA = 2.3 rabbits/km. We produced a land use map with metric precision using remote sensing. Water, bare soil, herbaceous, shrubs and trees were identified. Landscape structure and diversity were evaluated using variables available in FRAGSTATS. A logistic regression was performed to assess the link between rabbit presence/absence and landscape structure. Our results indicate that a suitable habitat has a high diversity, a medium number of patches and a small proportion of shrubs. These results could be used to diagnose the landscape prior to any management action to enhance rabbit populations and conversely be helpful as a tool of integrated control in the cases of local outbreaks with agricultural damages.

  11. Development of a rabbit model for a preclinical comparison of coronary stent types in-vivo.

    Science.gov (United States)

    Lee, Joo Myung; Lee, Jaewon; Jeong, Heewon; Choe, Won Seok; Seo, Won-Woo; Lim, Woo-Hyun; Kim, Young-Chan; Hur, Jin; Lee, Sang Eun; Yang, Han-Mo; Cho, Hyun-Jai; Kim, Hyo-Soo

    2013-11-01

    Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.

  12. Comparative analysis of the nuclear basic proteins in rat, human, guinea pig, mouse and rabbit spermatozoa.

    Science.gov (United States)

    Calvin, H I

    1976-06-15

    Cysteine-rich protamines (Arg = 47-61%, Cys = 8-16%) were isolated from the sperm of an individual guinea pig, human and rabbit and from pooled samples of mouse and rat sperm. Appreciable concentrations of histones were not found in the sperm nuclei of these species. In addition to the protamines, a substance of relatively low molecular weight, which reacted with the Lowry reagent, appeared in crude acid-soluble extracts of sperm nucleoprotein. This unidentified contaminent was resolved from the protamines by chromatography on Bio-Rex 70. Heterogeneity of human and mouse protamines was revealed by electrophoresis at pH 2.7, in the presence of 2.5 M urea, and confirmed by amino acid analysis, which also suggested the presence of 2 or more species of protamine in the rabbit. By contrast, the guinea pig and rat preparations displayed nearly stoichiometric ratios of amino acid residues, approaching homogeneity by this criterion. The functional consequences of crosslinks between cysteine residues of these proteins and the possible species-specific significance of their differing percentages of histidine are discussed. Potentially analogous functions are suggested for phosphorylated serine and threonine, and for ionized cysteine and tyrosine, within the protamines of developing spermatids. Their amino acid compositions indicate that the protamines of eutherian mammals are coded by a C.G-rich genome which has been unusually susceptible to genetic drift. An especially high rate of G leads to A transitions seems to have occurred in the human protamine genes.

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

    Science.gov (United States)

    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.

  14. Molecular Dynamics Studies on the Structural Stability of Wild-Type Rabbit Prion Protein: Surface Electrostatic Charge Distributions

    CERN Document Server

    Zhang, Jiapu

    2011-01-01

    Prion diseases cover a large range of neurodegenerative diseases in humans and animals, which are invariably fatal and highly infectious. By now there have not been some effective therapeutic approaches or medications to treat all prion diseases. Fortunately, numerous experimental experiences have showed that rabbits are resistant to infection from prion diseases isolated from other species, and recently the molecular structures of rabbit prion protein and its mutants were released into protein data bank. Prion diseases are "protein structural conformational" diseases. Thus, in order to reveal some secrets of prion diseases, it is amenable to study rabbits by techniques of the molecular structure and its dynamics. Wen et al. (PLoS One 5(10) e13273 (2010), Journal of Biological Chemistry 285(41) 31682-31693 (2010)) reported the surface of NMR RaPrPC(124-228) molecular snapshot has a large land of continuous positive charge distribution, which contributes to the structural stability of rabbit prion protein. Thi...

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

    Science.gov (United States)

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

    2016-10-01

    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. 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. Distraction osteogenesis was carried out successfully in all rabbits when the device used to distract the rib up to 4 cm. 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.

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

    Science.gov (United States)

    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, pcontrols. 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.

  17. Study of Topical Human Umbilical Cord Blood Serum in the Treatment of Alkaline Corneal Epithelial Wounds in Rabbit Model

    Directory of Open Access Journals (Sweden)

    B Sharifi

    2011-04-01

    Full Text Available Introduction & Objective: One of the important functions of the cornea is to maintain normal vision by refracting light onto the lens and retina. This property is dependent in part on the ability of the corneal epithelium to undergo continuous renewal. Ocular surface failure which follows a variety of endogenous and exogenous precipitating factors, the most common being: chemical trauma, infection, alkaline burn, inflammation and hereditary conditions, lid or lash abnormalities, tear deficiency or reduced sensation. The core principal underpinning management strategy for ocular surface failure is establishing or promoting new growth of healthy conjunctiva and corneal epithelium. This process is mediated by many proteins that are inducers of corneal cell migration, proliferation, and differentiation. The current study was performed to investigate the efficacy of umbilical cord serum on alkaline corneal epithelial wound healing in the rabbit model. Materials & Methods: In this study conducted at Yasuj University of Medical Sciences in 2010, thirty two rabbits were randomly assigned into two equal groups. Central corneal alkali wound was formed in one eye of the rabbits by applying a 6-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. Group one of animals received umbilical cord blood serum and group two received Sno*Tear in the eyes. The treatment was dosed 4 times a day with the eye drops, and epithelial wound closure was recorded using slit lamp. The data were analyzed to determine the rate of wound closure. Results: The mean wound radius closure rate was 0.77 mm/day (SD=0.013 for umbilical cord blood serum-treated eyes, 0.73 mm/day (SD=0.018 for artificial tear-treated eyes. Conclusion: This study shows that alkali-injured corneal epithelial wound heal faster when treated with umbilical cord blood serum than with artificial tear in rabbit model.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Local administration of growth hormone enhances periimplant bone reaction in an osteoporotic rabbit model.

    Science.gov (United States)

    Tresguerres, Isabel F; Clemente, Celia; Donado, Manuel; Gómez-Pellico, Luis; Blanco, Luis; Alobera, Miguel Angel; Tresguerres, Jesús A F

    2002-12-01

    The purpose of this study was to determine whether rhGH administered locally during the surgical placement of an implant, in the tibia of an osteoporotic rabbit model, would induce qualitative and quantitative differences in peri-implant bone reaction. Eight New Zealand rabbits were ovariectomized and fed with a low-calcium diet (with 0.07% of calcium) to induce osteoporosis. After 6 weeks, an experimental titanium sheet was inserted into the rabbit tibiae. The rabbits were randomly divided into two groups. The experimental group was treated with 4 IU of rhGH added locally into the ostectomy as a lyophilized powder and the control group was left without any treatment. After 2 weeks, animals were sacrificed, tibial sections were prepared and bone-titanium interface was examined at light microscopy, using Masson, hematoxylin-eosin and Pichrosirius stains. Light microscopic morphometry and densitometry were used to comparatively quantitate bone reaction. Local administration of rhGH during the surgical placement of titanium sheets on the tibiae of an osteoporotic rabbit model enhances periosteal and transcortical reaction and mineralization of osteoid 14 days later around titanium sheets, without increasing bone resorption.

  20. Cloning of neuromedin B and its receptor in the rabbit and generating a polyclonal antibody to the neuromedin B protein.

    Science.gov (United States)

    Guo, Ting-Ting; Su, Juan; Ma, Zhi-Yu; Ma, Jun-Xiao; Jin, Meng-Meng; Li, Xiang; Lei, Zhi-Hai

    2015-06-10

    Neuromedin B (NMB) is a highly conserved bombesin-related neuropeptide found in mammals. Neuromedin B (NMB) executes its effect by binding to the cell surface receptor, neuromedin B receptor (NMBR). In this study, we cloned the rabbit NMB and NMBR genes. The similarity and phylogenetic analyses of NMB and NMBR gene sequences were performed. The expression of NMB and NMBR mRNA in the rabbit was investigated using real-time RT-PCR. Our bioinformatic analysis demonstrated that the cloned rabbit NMB precursor cDNA encoded Gly-His-Phe-Met-NH2 amino acids at the C-terminus, and that its receptor possessed typical transmembrane features. The NMB mRNA was highly expressed in the CNS, while the NMBR mRNA was widely expressed in many tissues, with the highest expression in the gastrointestinal tract. The studies on the NMB distribution and function are limited by the lack of a specific antibody to this neuropeptide. In this paper, polyclonal NMB antibody was generated in mice. Western blotting analysis revealed that the prepared antibody could specifically recognize the recombinant and the endogenous NMB proteins. Immunohistochemistry analysis indicated that the NMB protein was localized in the cytoplasm of the pituitary cells. The existence of NMB protein in the hypothalamic-pituitary-gonadal axis suggests that NMB might function in rabbit reproduction.

  1. Paclitaxel reduces formation of hypertrophic scars in the rabbit ear model

    Directory of Open Access Journals (Sweden)

    Huang LP

    2015-07-01

    Full Text Available Li-ping Huang,1* Guo-qi Wang,2* Zi-shan Jia,1 Jing-wen Chen,1 Gang Wang,1 Xing-lin Wang1   1Department of Physical Therapy, 2Department of Orthopedics, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Background and objective: The onset and progression of pathological scarring involves multiple cytokines and complex mechanisms. However, hyperplasia of fibroblasts and neovascularization plays important roles, which can be inhibited by paclitaxel. The aim of this study was to investigate the efficacy of paclitaxel in the treatment of hypertrophic scars on rabbit ears. Methods: Rabbit ear models of hypertrophic scars were established to observe the therapeutic effects of paclitaxel at different concentrations (12 mg/L, 24 mg/L, 48 mg/L, 96 mg/L, 18 mg/L, 54 mg/L, 162 mg/L, 486 mg/L, 30 mg/L, 150 mg/L, 750 mg/L, 3,750 mg/L. The outcome measures included hypertrophic index (HI, density of fibroblasts, density of collagenous fibers, and microvessel density. Results: In comparison with the control group, the concentrations of 96 mg/L, 150 mg/L, and 162 mg/L significantly reduce the formation of hypertrophic scars in the rabbit ear models. However, local necrosis was found in the rabbit ear models treated with paclitaxel solution >400 mg/L. Conclusion: Paclitaxel has strong inhibitory effects on the hyperplasia of fibroblasts, deposition of collagen, and microangiogenesis in hypertrophic scars on rabbit ears within the concentration range from 48 mg/L to 162 mg/L, without causing local necrosis. Keywords: hypertrophic scar, paclitaxel, rabbit ear model

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

    Institute of Scientific and Technical Information of China (English)

    Cang-Song XIAO; Chang-Qing GAO; Li-Bing LI; Yao WANG; Tao ZHAO; Wei-Hua YE; Chong-Lei REN; Zhi-Yong LIU; Yang WU

    2014-01-01

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

  3. Serum level of high-sensitivity C-reactive protein in a rabbit model of atherosclerosis following repeated long-term exposure to positive acceleration%重复长时间正加速度暴露动脉粥样硬化家兔模型血清超敏C-反应蛋白的变化

    Institute of Scientific and Technical Information of China (English)

    罗慧兰; 陈勇胜

    2012-01-01

    BACKGROUND: Serum levels of high-sensitivity C-reactive protein (hs-CRP) can be used to predict cardiovascular injury.OBJECTIVE: To investigate the serum levels of hs-CRP in a rabbit model of atherosclerosis following repeated long-termexposure to positive acceleration and to predict the risk of cardiovascular injury.METHODS: Twenty-four New Zealand purebred rabbits were randomly divided into a positive acceleration group and a controlgroup. Rabbits in the positive acceleration group were exposed to +4 g rotation for 20 seconds with an acceleration of 1 g/s. Therotation interval was 5 minutes and totally three rotations were daily performed for 3 days per week. 0.5 g rotation was addedevery week, and by week 4, +6 g rotation was added, and the exposure lasted for 40 seconds.RESULTS AND CONCLUSION: Exposure to positive acceleration yielded significant effects on serum level of hs-CRP in rabbitswith atherosclerosis compared with before exposure (P 0.05). The interaction between exposure to positive acceleration and exposure time also did not produce significanteffects on serum level of hs-CRP (P > 0.05). Hyperplastic foam cells in the aortic tunica intima and the superficial layer of mediaincreased with the prolongation of exposure to positive acceleration. Repeated long-term exposure to positive acceleration maylead to a long-term high serum level of hs-CRP in rabbits.%背景:血清超敏C-反应蛋白的水平能够预测心血管损伤.目的:探讨重复正加速度暴露时动脉粥样硬化模型家兔血清超敏C-反应蛋白的变化与心血管损伤的风险预测.方法:将24 只新西兰纯种兔随机等分为正加速度组和对照组.正加速度组兔先在+4 g 水平(持续20 s,增长率为1 g/s)下暴露,旋转间隔时间为5 min,连续旋转3 次,每周3 d.每周增加0.5 g,至第4 周时增加至+6 g,持续暴露40 s.差异也无显著性意义(P > 0.05).兔主动脉内膜下及中膜浅层增生的泡沫细胞量随正加速度暴露的延长

  4. Bovine leukemia virus structural gene vectors are immunogenic and lack pathogenicity in a rabbit model.

    Science.gov (United States)

    Kucerova, L; Altanerova, V; Altaner, C; Boris-Lawrie, K

    1999-10-01

    Infection with a replication-competent bovine leukemia virus structural gene vector (BLV SGV) is an innovative vaccination approach to prevent disease by complex retroviruses. Previously we developed BLV SGV that constitutively expresses BLV gag, pol, and env and related cis-acting sequences but lacks tax, rex, RIII, and GIV and most of the BLV long terminal repeat sequences, including the cis-acting Tax and Rex response elements. The novel SGV virus is replication competent and replicates a selectable vector to a titer similar to that of the parental BLV in cell culture. The overall goal of this study was to test the hypothesis that infection with BLV SGV is nonpathogenic in rabbits. BLV infection of rabbits by inoculation of cell-free BLV or cell-associated BLV typically causes an immunodeficiency-like syndrome and death by 1 year postinfection. We sought to evaluate whether in vivo transfection of BLV provirus recapitulates pathogenic BLV infection and to compare BLV and BLV SGV with respect to infection, immunogenicity, and clinical outcome. Three groups of rabbits were subjected to in vivo transfection with BLV, BLV SGV, or negative control DNA. The results of our 20-month study indicate that in vivo transfection of rabbits with BLV recapitulates the fatal BLV infection produced by cell-free or cell-associated BLV. The BLV-infected rabbits exhibited sudden onset of clinical decline and immunodeficiency-like symptoms that culminated in death. BLV and BLV SGV infected peripheral blood mononuclear cells and induced similar levels of seroconversion to BLV structural proteins. However, BLV SGV exhibited a reduced proviral load and did not trigger the immunodeficiency-like syndrome. These results are consistent with the hypothesis that BLV SGV is infectious and immunogenic and lacks BLV pathogenicity in rabbits, and they support the use of this modified proviral vector delivery system for vaccines against complex retroviruses like BLV.

  5. Use of a Rabbit Soft Tissue Chamber Model to Investigate Campylobacter jejuni - Host Interactions

    Directory of Open Access Journals (Sweden)

    Annika eFlint

    2010-11-01

    Full Text Available Despite the prevalence of C. jejuni as an important food borne pathogen, the microbial factors governing its infection process are poorly characterized. In this study, we developed a novel rabbit soft tissue chamber model to investigate C. jejuni interactions with its host. The in vivo transcriptome profile of C. jejuni was monitored as a function of time post-infection by competitive microarray hybridization with cDNA obtained from C. jejuni grown in vitro. Genome-wide expression analysis identified 449 genes expressed at significantly different levels in vivo. Genes implicated to play important roles in early colonization of C. jejuni within the tissue chamber include up-regulation of genes involved in ribosomal protein synthesis and modification, heat shock response, and primary adaptation to the host environment (DccSR regulon. Genes encoding proteins involved in the TCA cycle and flagella related components were found to be significantly down regulated during early colonization. Oxidative stress defense and stringent response genes were found to be maximally induced during the acute infectious phase. Overall, these findings reveal possible mechanisms involved in adaptation of Campylobacter to the host.

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    Background:Stellate ganglion (SG) plays an important role in cardiovascular diseases.The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system.The aim of this research was to evaluate the effects offluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia (MI).Methods:The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits.Using whole-cell patch clamp technique,we studied the characteristic changes of ion channels and action potentials (APs) in isolated SG neurons in control group (n =20),MI group (n =20) and fluvastatin pretreated group (fluvastatin group,n =20),respectively.The protein expression of sodium channel in SG was determined by immunohistochemical analysis.Results:MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents.The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves,inactivation curves,and recovery curves after inactivation were changed in the MI group.The peak current densities of control group,MI group,and fluvastatin group (n =10 in each group) were-71.77 ± 23.22 pA/pF,-126.75 ± 18.90 pA/pF,and-86.42 ± 28.30 pA/pF,respectively (F=4.862,P =0.008).Fluvastatin can decrease the current amplitude which has been increased by MI.Moreover,fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group.But the expression of sodium channel-associated protein (Nav 1.7) had no significantly statistical difference among the three groups.The percentages of Nav 1.7 protein in control group,MI group,and fluvastatin group (n =5 in each group) were 21.49 ± 7.33%,28.53 ± 8.26%,and 21.64 ± 2.78%,respectively (F =1.495,P =0.275).Moreover,MI reduced the electrical activity of AP and increased amplitude of AP

  8. Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus

    Science.gov (United States)

    2016-01-01

    Purpose The purpose of the present study was to evaluate the effectiveness of a minimal concentration of bone morphogenetic protein-2 (BMP-2) in terms of quantitative and qualitative analyses of newly formed bone in a rabbit maxillary sinus model. Methods In 7 rabbits, sinus windows were prepared bilaterally. Biphasic calcium phosphate (BCP) loaded with 0.05 mg/mL BMP-2 was grafted into one sinus (the BMP group) and saline-soaked BCP was placed into the other (the control group) in each animal. The animals were allowed an 8-week healing period before being sacrificed. Specimens including the augmented area and surrounding tissues were then removed and evaluated both radiographically and histologically. Results There was a difference in the mineralization of new bone between the groups. In the BMP group, the greater part of the new bone consisted of mature lamellar bone with an evident trabecular pattern, whereas the control group showed mostly woven bone, consisting only partially of lamellar bone. Histometrically, the area of new bone was significantly greater (4.55±1.35 mm2 vs. 2.99±0.86 mm2) in the BMP group than in the control group (Pmineralization in a rabbit sinus model using a BCP carrier. PMID:27800217

  9. Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein.

    Science.gov (United States)

    Ngo, Doan T M; Stafford, Irene; Kelly, Darren J; Sverdlov, Aaron L; Wuttke, Ronald D; Weedon, Helen; Nightingale, Angus K; Rosenkranz, Anke C; Smith, Malcolm D; Chirkov, Yuliy Y; Kennedy, Jennifer A; Horowitz, John D

    2008-08-20

    Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, Pvitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.

  10. MODELS OF PROTEIN FOLDING

    Directory of Open Access Journals (Sweden)

    Unnati Ahluwalia

    2012-12-01

    Full Text Available In an attempt to explore the understanding of protein folding mechanism, various models have been proposed in the literature. Advances in recent experimental and computational techniques rationalized our understanding on some of the fundamental features of the protein folding pathways. The goal of this review is to revisit the various models and outline the essential aspects of the folding reaction.

  11. Persistent Penumbra in a Rabbit Stroke Model: Incidence and Histologic Characteristics

    Directory of Open Access Journals (Sweden)

    Leah J. Hennings

    2011-01-01

    Full Text Available Duration and extent of penumbra determine the window and brain volume in which interventions may save injured tissue after stroke. Understanding the penumbra in animals is necessary in order to design models that translate to effective clinical therapies. New Zealand white rabbits were embolized with aged autologous clot (n=23 or insoluble microspheres (n=21. To examine effects of treatment on penumbra, sphere-stroked animals were treated with 3 μm microbubbles plus ultrasound (n=19. Rabbits were euthanized at 4 or 24 hr. Infarct volume was measured following triphenyltetrazolium chloride (TTC staining of brain sections. Penumbra was visualized using immunostaining of pimonidazole injected fifteen minutes prior to euthanasia. Potentially reversible penumbra was present in 14.3% stroked rabbits at 4 hours and 15.7% at 24 hours after embolic stroke and represented up to 35% of total lost tissue. Intervention at up to 24 hours may benefit a significant patient population.

  12. Effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

    Institute of Scientific and Technical Information of China (English)

    Zhao-Xun Pan; Hong-Xin Zhang; Ye-Xin Wang; Long-Di Zhai; Wei Du

    2014-01-01

    Objective:To observe the effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis. Methods: Bilateral femoral head necrosis models of rabbit were established by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4 groups: Group A, control group with12 rabbits, 24 femoral head necrosis;Group B, treated with rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis;Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral head necrosis;Group D treated with core depression group without implantation, with 12 rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the defect regions were used to evaluate the level of ossification. The morphologic change and bone formation was assessed by HE staining. The angiogenesis was evaluated by VEGF immunohistochemistry. Results: The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in group B was better than other groups. Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D. Conclusions:The treatment of rhBMP-2/PLGA implantation after core depression can promote the repair of rabbit femoral head necrosis. It is a promising and efficient synthetic bone material to treat the femoral head necrosis.

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

    Science.gov (United States)

    Baydin, A; Cokluk, C; Aydin, K

    2007-06-01

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

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

    Science.gov (United States)

    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.

  15. Fenestration defects in the rabbit jaw: an inadequate model for studying periodontal regeneration.

    Science.gov (United States)

    Oortgiesen, Daniel A W; Meijer, Gert J; Bronckers, Antonius L J J; Walboomers, X Frank; Jansen, John A

    2010-02-01

    Periodontitis is an inflammatory disease affecting the support of the teeth, eventually leading to loosening and subsequent loss of teeth. Effective procedures for periodontal tissue engineering or regeneration require preclinical models before market introduction. Research has been performed in either small or large animals. Unfortunately, there is no intermediate-sized in vivo model available for periodontal regeneration studies, such as, for instance, rabbits. The objective of this study was to evaluate the rabbit as a new experimental model to study periodontal regeneration. In 12 rabbits, periodontal defects were created in a 4 x 6 mm bone window. The animals were sacrificed after 2, 4, 6, 8, 10, and 12 weeks. Up to 6 weeks, the fenestration defects healed partly by repair and partly by regeneration. After 6 weeks the root had erupted to such an extent that the original root defect shifted into the oral cavity. This signifies that the periodontal ligament (PDL) bordering the original bone defect site is newly formed during the natural eruption process and not locally regenerated. Apparently, the new PDL originates from mesenchymal cells that arise from the apical part (sheath of Hertwig) and subsequently developed into PDL fibroblasts. At 12 weeks, no signs of surgery were present anymore. On the basis of our observation that the defect of the PDL was replaced rather than restored, we conclude that the rabbit model has disadvantages and is less suitable for studies of regeneration of PDL.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  18. AN IMMUNOCYTOCHEMICAL STUDY OF BONEMORPHOGENETIC PROTEIN IN EXPERIMENTAL FRACTURE HEALING OF THE RABBIT MANDIBLE

    Institute of Scientific and Technical Information of China (English)

    金岩; 杨连甲; FrankH.White

    1994-01-01

    A monoclonal antibody raised against bone morphogenetic protein (BMP-McAb)has been used to demonstrate the presence of bone mrphogenetic protein(BMP) in experimental fracture healing.Rabbit mandibles were frac-tured using standrdized methods and left to heal for 3,7,14,21and 24 d,respectively.The avidin-biotin com- plex(ABC)method demonstrated an accumulation of positively stained primitive mesenchyman cells at the fracture site in the hematoma stage of bone repair.These cells appeared to undergo differentiation into positively-stained chondroblasts and osteoblasts during the phase of callus formation.Undifferentiated mesenchymal cells showed a high positive reactivity in the early post-fracture stages but a much lower reactivity during the remodelling phase.The results of our study suggest that bone inductive processes are accompanied by the presence of BMP in osteopro-genitor cells during fracture healing of the mandible and that BMP may plqy a significant role in osteogenesis dur-ing bone healing.

  19. Corticosteroids and immunosuppressive agents in rabbit heterolamellar corneal transplant model.

    Science.gov (United States)

    Ohia, E; Kulkarni, P

    1991-09-01

    Bovine cornea (epithelium and stroma) was transplanted on to the rabbit cornea from which the epithelium and stroma had been removed. Conjuntival hyperemia and edema occurred from day 1-5 post-operation, followed by neovascularization and graft rejection within 7-10 days. Topical dexamethasone (0.1%) and prenisolone (1%) t.i.d. inhibited post-surgical hyperemia, edema, delayed hypersensitivity and neovascularization. These agents and the immunosuppressants (cyclosporin A and rapamycin) inhibited graft rejection observed up to 20 days. After cessation of treatment on the 20th day, grafts remained viable up to 35 days with dexamethasone, 10 days with prednisolone and rapamycin, and 5 days with cyclosporin A.

  20. Phosphorylation of anchoring protein by calmodulin protein kinase associated to the sarcoplasmic reticulum of rabbit fast-twitch muscle.

    Science.gov (United States)

    Damiani, E; Sacchetto, R; Margreth, A

    2000-12-09

    Regulatory phosphorylation of phospholamban and of SR Ca(2+)-ATPase SERCA2a isoform by endogenous CaM-K II in slow-twitch skeletal and cardiac sarcoplasmic reticulum (SR) is well documented, but much less is known of the exact functional role of CaM K II in fast-twitch muscle SR. Recently, it was shown that RNA splicing of brain-specific alpha CaM K II, gives rise to a truncated protein (alpha KAP), consisting mainly of the association domain, serving to anchor CaM K II to SR membrane in rat skeletal muscle [Bayer, K.-U., et al. (1998) EMBO J. 19, 5598-5605]. In the present study, we searched for the presence of alpha KAP in sucrose-density purified SR membrane fractions from representative fast-twitch and slow-twitch limb muscles, both of the rabbit and the rat, using immunoblot techniques and antibody directed against the association domain of alpha CaM K II. Putative alpha KAP was immunodetected as a 23-kDa electrophoretic component on SDS-PAGE of the isolated SR from fast-twitch but not from slow-twitch muscle, and was further identified as a specific substrate of endogenous CaM K II, in the rabbit. Immunodetected, (32)P-labeled, non-calmodulin binding protein, behaved as a single 23-kDa protein species under several electrophoretic conditions. The 23-kDa protein, with defined properties, was isolated as a complex with 60-kDa delta CaM K II isoform, by sucrose-density sedimentation analysis. Moreover, we show here that putative alphaKAP, in spite of its inability to bind CaM in ligand blot overlay, co-eluted with delta CaM K II from CaM-affinity columns. That raises the question of whether CaM K II-mediated phosphorylation of alpha KAP and triadin together might be involved in a molecular signaling pathway important for SR Ca(2+)-release in fast-twitch muscle SR.

  1. Protein Model Database

    Energy Technology Data Exchange (ETDEWEB)

    Fidelis, K; Adzhubej, A; Kryshtafovych, A; Daniluk, P

    2005-02-23

    The phenomenal success of the genome sequencing projects reveals the power of completeness in revolutionizing biological science. Currently it is possible to sequence entire organisms at a time, allowing for a systemic rather than fractional view of their organization and the various genome-encoded functions. There is an international plan to move towards a similar goal in the area of protein structure. This will not be achieved by experiment alone, but rather by a combination of efforts in crystallography, NMR spectroscopy, and computational modeling. Only a small fraction of structures are expected to be identified experimentally, the remainder to be modeled. Presently there is no organized infrastructure to critically evaluate and present these data to the biological community. The goal of the Protein Model Database project is to create such infrastructure, including (1) public database of theoretically derived protein structures; (2) reliable annotation of protein model quality, (3) novel structure analysis tools, and (4) access to the highest quality modeling techniques available.

  2. Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome

    DEFF Research Database (Denmark)

    Diness, Thomas G; Yeh, Yung-Hsin; Qi, Xiao Yan;

    2008-01-01

    effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, I(Kr), in two rabbit models of acquired LQTS. METHODS AND RESULTS: We used two clinically relevant in vivo rabbit models of TdP in which we infused NS1643 or vehicle: (i) three-week atrioventricular block...... with ventricular bradypacing; (ii) dofetilide-induced I(Kr) inhibition in methoxamine-sensitized rabbits. In addition, we studied effects on ionic currents in cardiomyocytes with I(Kr) suppressed by bradycardia remodelling or dofetilide exposure. Bradypaced rabbits developed QT interval prolongation, spontaneous...... ventricular ectopy, and TdP. Infusion of NS1643 completely suppressed arrhythmic activity and shortened the QT interval; vehicle had no effect. NS1643 also suppressed ventricular tachyarrhythmias caused by infusion of dofetilide to methoxamine-sensitized rabbits, and reversed dofetilide-induced QT...

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

    Science.gov (United States)

    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.

  4. A modified rabbit model of stroke: evaluation using clinical MRI scanner.

    Science.gov (United States)

    Yang, Ji-Ping; Liu, Huai-Jun; Liu, Rui-Chun

    2009-12-01

    Occluding the middle cerebral artery of small animals with an intraluminal filament to build a stroke model has gained increasing acceptance. In light of the growing demand for magnetic resonance imaging (MRI) studies using the clinical MRI scanner, large animal models can be superior to small animal models. In this work, we developed a modified rabbit model of stroke, which was assessed using clinical MRI scanner and compared with a most commonly silicone-coated filament model. We presented a focal cerebral ischemia in rabbits. The key feature of this modified method is the use of a guide wire as a 'nylon suture'. At 3 days after ischemia, the percentage of brain infarct volume, neurobehavioral score, intracranial hemorrhagic incidence and dynamic changes of T(2) and apparent diffusion coefficient values were assessed respectively and compared between the focal cerebral models. Wire-induced models had more severe brain infarct size with less dispersion (32.7 +/- 6.5%, coefficient of variation=0.20) than that with filament models (25.4 +/- 8.9%, coefficient of variation=0.31; pwire, 20/20; filament, 17/20) and less intracranial hemorrhage (wire, 0/20; filament, 3/20) in wire-induced models than in filament-induced rabbits (pwire-induced method can provide a useful tool for the earlier research of ischemia.

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

    Science.gov (United States)

    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.

  6. Multimodal imaging of vocal fold scarring in a rabbit model by multiphoton microscopy

    Science.gov (United States)

    Kazarine, Alexei; Bouhabel, Sarah; Douillette, Annie H.; Kost, Karen; Li-Jessen, Nicole Y. K.; Mongeau, Luc; Wiseman, Paul W.

    2017-02-01

    Vocal fold scarring as a result of injury or disease can lead to voice disorders which can significantly affect the quality of life. During the scarring process, the normally elastic tissue of the vocal fold lamina propria is replaced by a much stiffer collagen-based fibrotic tissue, which impacts the fold's ability to vibrate. Surgical removal of this tissue is often ineffective and can result in further scarring. Injectable biomaterials, a form of tissue engineering, have been proposed as a potential solution to reduce existing scars or prevent scarring altogether. In order to properly evaluate the effectiveness of these new materials, multiphoton microscopy emerges as an effective tool due to its intrinsic multiple label free contrast mechanisms that highlight extracellular matrix elements. In this study, we evaluate the spatial distribution of collagen and elastin fibers in a rabbit model using second harmonic generation (SHG), third harmonic generation (THG) and two photon autofluorescence (TPAF) applied to unlabeled tissue sections. In comparison to traditional methods that rely on histological staining or immunohistochemistry, SHG, THG and TPAF provide a more reliable detection of these native proteins. The evaluation of collagen levels allows us to follow the extent of scarring, while the presence of elastin fibers is thought to be indicative of the level of healing of the injured fold. Using these imaging modalities, we characterize the outcome of injectable biomaterial treatments in order to direct future treatments for tissue engineering.

  7. Establishment of a blunt impact-induced brain injury model in rabbits

    Directory of Open Access Journals (Sweden)

    LI Kui

    2012-04-01

    Full Text Available 【Abstract】 Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine. Methods: Twenty-four New Zealand white rabbits were randomly divided into control group (n=4, minor injury group (n=10 and severe injury group (n=10. Based on the BIM-Ⅱ Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of intracranial pressure (ICP during the impact-ing process by pressure microsensors. Six hours after injury, all the rabbits were dissected to observe the injury mor-phology and underwent routine pathological examination. Results: Varying degrees of nervous system positive signs were observed in all the injured rabbits. Within 6 hours, the mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group. Morphological changes con-sisted of different levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma, subarachnoid hemo-rrhage and brain injury. At the moment of hitting, the ICP was greater in severe injury group than in mild injury group; and within the same group, the impact side showed positive pressure while the opposite side showed negative pressure. Conclusions: Under the rigidly-controlled experimen-tal condition, this animal model has a good reproducibility and stable results. Meanwhile, it is able to simulate the mor-phology of iron strike-induced injury, thus can be used to study the mechanism of blunt head injury in forensic medicine. Key words: Brain injuries; Forensic medicine; Wounds, nonpenetrating; Models, animal; Rabbits

  8. Molecular dynamics studies on the NMR structures of rabbit prion protein wild-type and mutants: surface electrostatic charge distributions

    CERN Document Server

    Zhang, Jiapu

    2014-01-01

    Prion is a misfolded protein found in mammals that causes infectious diseases of the nervous system in humans and animals. Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elk and humans etc. Recent studies have shown that rabbits have a low susceptibility to be infected by prion diseases with respect to other animals including humans. The present study employs molecular dynamics (MD) means to unravel the mechanism of rabbit prion proteins (RaPrPC) based on the recently available rabbit NMR structures (of the wild-type and its two mutants of two surface residues). The electrostatic charge distributions on the protein surface are the focus when analysing the MD trajectories. It is found that we can conclude that surface electrostatic charge distributions indeed contribute to the structural stability of wild-type RaPrPC; this may be useful for the medicinal treatment of prion diseases.

  9. RABBIT EARS, encoding a SUPERMAN-like zinc finger protein, regulates petal development in Arabidopsis thaliana.

    Science.gov (United States)

    Takeda, Seiji; Matsumoto, Noritaka; Okada, Kiyotaka

    2004-01-01

    Floral organs usually initiate at fixed positions in concentric whorls within a flower. Although it is understood that floral homeotic genes determine the identity of floral organs, the mechanisms of position determination and the development of each organ have not been clearly explained. We isolated a novel mutant, rabbit ears (rbe), with defects in petal development. In rbe, under-developed petals are formed at the correct position in a flower, and the initiation of petal primordia is altered. The rbe mutation affects the second whorl organ shapes independently of the organ identity. RBE encodes a SUPERMAN-like protein and is located in the nucleus, and thus may be a transcription factor. RBE transcripts are expressed in petal primordia and their precursor cells, and disappeared at later stages. When cells that express RBE are ablated genetically, no petal primordia arise. RBE is not expressed in ap1-1 and ptl-1 mutants, indicating that RBE acts downstream of AP1 and PTL genes. These characteristics suggest that RBE is required for the early development of the organ primordia of the second whorl.

  10. Absence of force suppression in rabbit bladder correlates with low expression of heat shock protein 20

    Directory of Open Access Journals (Sweden)

    Murphy Richard A

    2005-11-01

    Full Text Available Abstract Background Nitroglycerin can induce relaxation of swine carotid artery without sustained reductions in [Ca2+]i or myosin regulatory light chain (MRLC phosphorylation. This has been termed force suppression and been found to correlate with ser16-phosphorylation of heat shock protein 20 (HSP20. We tested for the existence of this mechanism in a smooth muscle that is not responsive to nitric oxide. Methods Isometrically mounted mucosa free rabbit bladder strips were contracted with carbachol and relaxed with 8-Br-cGMP, forskolin, or isoprenaline. Results Contraction was associated with a highly cooperative relation between MRLC phosphorylation and force such that very small increases in MRLC phosphorylation induced large increases in force. Relaxation induced by 8-Br-cGMP, forskolin, or isoprenaline did not shift the MRLC phosphorylation-force relation from that observed with carbachol alone, i.e. there was no force suppression. HSP20 content was negligible (approximately two hundred-fold less than swine carotid. Conclusion The lack of force suppression in the absence of HSP20 is consistent with the hypothesized role for HSP20 in the force suppression observed in tonic smooth muscles.

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

    Science.gov (United States)

    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. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  13. Increasing thickness and fibrosis of the cartilage in acetabular dysplasia: a rabbit model research

    Institute of Scientific and Technical Information of China (English)

    LI Tian-you; MA Rui-xue

    2010-01-01

    Background The order and mechanism of pathological changes in acetabular dysplasia are still unclear. This study investigated cartilage changes in rabbit acetabular dysplasia models at different ages.Methods Twenty-seven 1-month-old New Zealand rabbits underwent cast immobilization of the left hind limb in knee extension. Serial acetabular dysplasia models were established by assessment of the acetabular index and Sharp's angle on radiographs. The thickness of the acetabular cartilage was measured under a microscope, and fibrosis was observed. Ultrastructural changes were investigated with scanning electron microscopy and transmission electron microscopy. The messenger RNA expression of collagen Ⅰ and Ⅱ, β1 integrin, and caspase-9 were measured by real-time fluorescence quantitative polymerase chain reaction.Results In an immature group of rabbits, the acetabular index of the treated hip increased with animal growth. The cartilage on the brim of the left acetabulum was significantly thicker than that on the right side. The collagen fibrils on the surface of the cartilage became gross, and the chondrocytes in the enlargement layer underwent necrosis. In a mature group of rabbits, the left Sharp's angle increased in the rabbits with 6-week casting. The cartilage on the brim of the left acetabulum underwent fibrosis. The chondrocytes were weakly stained, and the number of lysosomes was much larger than normal. The messenger RNA expression of collagen Ⅰ and Ⅱ, β1 integrin, and caspase-9 in the cartilage differed significantly at different ages.Conclusions Increasing thickness followed by fibrosis may be the order of pathological cartilage changes in acetabular dysplasia, with changes in ultrastructure and collagen expression contributing to the process.

  14. Ultrastructural changes of the peritoneum in a rabbit model of peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Jovanović Nataša

    2013-01-01

    Full Text Available Background/Aim. The number of patients with end-stage renal diseases treated with chronic dialysis is increasing over the last years. Long-term peritoneal dialysis is associated with progressive development of structural and functional alterations of peritoneal membrane. The aim of the study was to analyze ultrastructural alterations of mesothelial monolayer and submesothelial tissue in a modified nonuremic experimental model of peritoneal dialysis in rabbits. Methods. The study was performed on 5 healthy Chinchilla rabbits. Surgical procedures of implantation and removal of peritoneal catheter, prevention of catheter clothing, prevention of infection and dialysate instillation were performed according to previously described protocols. Peritoneal tissue samples were collected upon catheter placement and removal after a 5-week follow-up and processed for transmission electron microscopy (TEM examination. Results. The rabbits tolerated anesthesia, surgical procedure and the applied regimen of dialysate instillations well. The animals recovered completely and no adverse effects were noted. In the animals treated with peritoneal dialysis instillations, TEM revealed alterations of the mesothelial monolayer and submesothelial tissue. The mesothelial cells in direct contact with dialysis fluid were prone to shrinking. They lost the typical cobblestone morphology and assumed a flattened shape. The mesothelial cells were often detached from the basement membrane. These cells showed euchromatic nuclei, higher number of microvilli in their apical part and very numerous vesicles. A higher quantity of collagen fibers was noticed in the peritoneal lamina propria in close relation to the basement membrane of mesothelium. The nuclei of the fibroblasts were also euchromatic. Numerous mitochondria, granules and vesicles were present in their cytoplasm. Conclusion. The used rabbit model of peritoneal dialysis is simple, practical to perform, reproducible, not

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

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    J Casey Olson

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

  16. Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model.

    Science.gov (United States)

    Kim, Jinku; McBride, Sean; Donovan, Amy; Darr, Aniq; Magno, Maria Hanshella R; Hollinger, Jeffrey O

    2015-05-08

    The aim of the study was to determine bone regeneration in a rabbit radius critical-size defect (CSD) model using a specific polymer composition (E1001(1k)) from a library of tyrosine-derived polycarbonate scaffolds coated with a calcium phosphate (CP) formulation (E1001(1k) + CP) supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2). Specific doses of rhBMP-2 (0, 17, and 35 μg/scaffold) were used. E1001(1k) + CP scaffolds were implanted in unilateral segmental defects (15 mm length) in the radial diaphyses of New Zealand White rabbits. At 4 and 8 weeks post-implantation, bone regeneration was determined using micro-computed tomography (µCT), histology, and histomorphometry. The quantitative outcome data suggest that E1001(1k) + CP scaffolds with rhBMP-2 were biocompatible and promoted bone regeneration in segmental bone defects. Histological examination of the implant sites showed that scaffolds made of E1001(1k) + CP did not elicit adverse cellular or tissue responses throughout test periods up to 8 weeks. Noteworthy is that the incorporation of a very small amount of rhBMP-2 into the scaffolds (as low as 17 μg/defect site) promoted significant bone regeneration compared to scaffolds consisting of E1001(1k) + CP alone. This finding indicates that E1001(1k) + CP may be an effective platform for bone regeneration in a critical size rabbit radius segmental defect model, requiring only a minimal dose of rhBMP-2.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  18. Influence of Implant Surface Topography on Primary Stability in a Standardized Osteoporosis Rabbit Model Study

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    Hiroshi Oue

    2015-03-01

    Full Text Available Evaluating primary stability is important to predict the prognosis of dental implant treatment. Primary stability is decreased in a low bone density site such as osteoporosis. However, it is difficult to apply in small animal and the effect of the different implant surface topography for the primary stability at low bone density site has not yet fully been investigated. The purpose of the present study was to evaluate the influence of implant surface topography on primary stability in a standardized osteoporosis animal model. Six rabbits underwent ovariectomy and administrated glucocorticoid to induce an osteoporosis model. Sham-operations were performed in additional six rabbits. Implants with machined or oxidized-surfaces were inserted into the femur epiphyses and insertion torque (IT and implant stability quotient (ISQ were measured. In sham model, the IT and ISQ did not differ significantly between the both implant. However, the IT value of oxidized-surface implant was significantly higher than that of the machined implant in the osteoporosis model. Meanwhile, ISQ did not significantly differ between the machined and oxidized-surfaced implants. In conclusion, the IT of implants is higher with rough than with smooth surfaces but that there are no differences in ISQ value between different surfaces in a standardized osteoporosis bone reduced rabbit model.

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

    Science.gov (United States)

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

    2016-08-01

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

  20. Effect of calcium citrate on bone integration in a rabbit femur defect model

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Peng-Fei Nie; Xiu-Cui Li; Ferdinand An Rompis; Hang Huang; Hua Zhang; Zhong-Lin Mu; Lei Peng; Wei Wang; Qing-Yu Chen; Zhong-Qin Lin; Shao-Wen Cheng; Dong-Quan Kou; Xiao-Zhou Ying; Yue Shen; Xiao-Jie Cheng

    2012-01-01

    ABSTRACT Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (GroupA, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus6.0 software after animal was sacrificed at 4th(GroupA), 6th(GroupB) and8th(GroupC) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative4th and6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to2.0 mm. No statistical difference was observed when these defects were larger than2.0 mm at all healing periods except at the4th week.Conclusions: Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

  1. Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

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    Collard Fabien

    2010-01-01

    Full Text Available Abstract Background The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection rabbit model of osteoarthritis (OA and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA grading scale and associated radiographic atlas. Methods In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits. Results Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p s = 0.68 and rs = 0.58, p s = 0.64, p Conclusion Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.

  2. The angiotensin II type 1 receptor blocker losartan attenuates bioprosthetic valve leaflet calcification in a rabbit intravascular implant model.

    Science.gov (United States)

    Shin, Hong Ju; Kim, Dae-Hyun; Park, Han Ki; Park, Young Hwan

    2016-12-01

    There is evidence that angiotensin II type I receptor blocker (ARB) could reduce structural valve deterioration. However, the anticalcification effect on the bioprosthetic heart valve (BHV) has not been investigated. Thus, we investigated the effects of losartan (an ARB) on calcification of implanted bovine pericardial tissue in a rabbit intravascular implant model. A total of 16 male New Zealand White rabbits (20 weeks old, 2.98-3.34 kg) were used in this study. Commercially available BHV leaflet of bovine pericardium was trimmed to the shape of a 3-mm triangle and implanted to both external jugular veins of the rabbit. The ARB group (n = 8) was given 25 mg/kg of powdered losartan daily until 6 weeks after surgery by direct administration in the buccal pouch of the animals. The control group (n = 8) was given 5 ml of normal saline by the same method. After 6 weeks, quantitative calcium determination, histological evaluation and western blot analysis of interleukin-6 (IL-6), osteopontin and bone morphogenetic protein 2 (BMP-2) were performed to investigate the mechanisms of the anticalcification effect of losartan. No deaths or complications such as infection or haematoma were recorded during the experiment. All animals were euthanized on the planned date. The calcium measurement level in the ARB group (2.28 ± 0.65 mg/g) was significantly lower than that in the control group (3.68 ± 1.00 mg/g) (P = 0.0092). Immunohistochemistry analyses revealed that BMP-2-positive reactions were significantly attenuated in the ARB group. Western blot analysis showed that losartan suppressed the expression of IL-6, osteopontin and BMP-2. Our results indicate that losartan significantly attenuates postimplant degenerative calcification of a bovine pericardial bioprosthesis in a rabbit intravascular implant model. Further studies are required to assess the effects of ARBs on BHV tissue in orthotopic implantations using a large animal model. © The Author 2016. Published by Oxford

  3. A Review on the Salt Bridge Between ASP177 and ARG163 of Wild-Type Rabbit Prion Protein

    CERN Document Server

    Zhang, Jiapu

    2014-01-01

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered beta2-alpha2 loop [PLoS One 5 (10) e13273 (2010); Journal of Biological Chemistry 285 (41) 31682-31693 (2010)] and a helix-capping motif within this loop [PLoS One 8 (5) e63047 (2013)]. The beta2-alpha2 loop has been a focus in prion studies. For this loop we found a salt bridge linkage ASP177-ARG163 (O-N) [Journal of Theoretical Biology 342 (7 February 2014) 70-82 (2014)]. Some scientists said on the 2FJ3.pdb NMR file of the rabbit prion protein, the distance of ASP177-ARG163 (O-N) gives the salt bridge of about 10 angstroms which is nearly null in terms of energy thus think our result is wrong. This opinion is clearly wrong simply due to the 3O7...

  4. Distraction osteogenesis after irradiation in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Kenji [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-06-01

    Little is known about how preoperative irradiation delays distraction osteogenesis. The purpose of this study is to investigate the effect of preoperative irradiation on distraction osteogenesis. A single dose of 15 Gy irradiation was applied in a medial-to-lateral direction to the right rear legs of Japanese white rabbits. This was followed immediately by application of a unilateral external fixator and diaphyseal osteotomy of the tibia. Seven days later, lengthening of the tibia was initiated at a rate of 0.5 mm/day and continued for 4 weeks, with a total elongation of 14 mm. Radiographic and histological findings and microangiography were examined. Radiographs of the legs were obtained once a week. The animals were sacrificed at 0 and 4 weeks after completion of lengthening, and the tibia were subjected to histological examination and microangiography. Routine staining was performed with hematoxyline and eosin, and immunostaining with a vascular endothelial growth factor (VEGF) antibody. The radiographs showed little regeneration during the elongation phase. Although the callus appeared very slowly during the maturation phase, it did not show the usual three distinct zones, but only spotty callus formation. Furthermore, regeneration was not completed until the 4th week of the maturation period. The histological examination at the end of distraction showed a gap in the distraction, consisting of loose connective tissue with part of the fibrous tissue oriented longitudinally. There was no evidence of new mineralization. Four weeks after completion of distraction, the major part of the radiolucent region consisted of cartilage. There was no evidence of the normal regeneration pattern described in many previous reports. The spotty osteogenesis was identified as endochondral ossification. Immunochemical examination of the regeneration area revealed that the blood vessels were extremely localized, and that expression of VEGF in the osteoblasts was very high

  5. Surgical capsular release reduces flexion contracture in a rabbit model of arthrofibrosis.

    Science.gov (United States)

    Barlow, Jonathan D; Hartzler, Robert U; Abdel, Matthew P; Morrey, Mark E; An, Kai-Nan; Steinmann, Scott P; Morrey, Bernard F; Sanchez-Sotelo, Joaquin

    2013-10-01

    Animal models of joint contracture may be used to elucidate the mechanisms of arthrofibrosis. Patients with joint contracture commonly undergo surgical capsular release. Previous animal models of joint contracture do not simulate this aspect of arthrofibrosis. We hypothesize that a surgical capsular release will decrease the severity of arthrofibrosis in this rabbit model. A capsular contracture was surgically created in 20 skeletally mature rabbits. Eight weeks later, ten rabbits underwent capsular release, which consisted of elevation of the posterior capsule through a lateral incision and manipulation under anesthesia. Ten rabbits had a sham incision, without release (control group). Immediately after release or sham surgery, extension loss (calculated by subtracting the knee extension angle (degrees) of the operative limb from the nonoperative, contralateral limb) was measured using fluoroscopy. All animals were sacrificed following 16 weeks of postoperative free cage activity. At sacrifice, joint contracture was measured using a custom, calibrated device. The histology of the posterior joint capsule was assessed at sacrifice. All animals survived both operations without complications. Immediately after surgical release or sham surgery, the average extension loss was 129.2 ± 10.7° in the control group versus 29.6 ± 8.2° in the capsular release group (p = 0.0002). Following 16 weeks of remobilization, the average extension loss of the control and capsular release animals were 49.0 ± 12.7° and 36.5 ± 14.2°, respectively (p = 0.035). There were no histological differences between the two groups. In this animal model, a surgical capsular release decreased the extension loss (flexion contracture) immediately after surgery, as well as following sixteen weeks of remobilization. There were no histological changes detected in the posterior joint capsule. Copyright © 2013 Orthopaedic Research Society.

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

    OpenAIRE

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

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  7. ANTIGENICITY OF COW'S MILK PROTEINS IN TWO ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    T.R. Neyestani

    2000-08-01

    Full Text Available Antigenicity of proteins found in cow's milk is age dependent. This is primarily due to infants possessing a more permeable intestinal wall than that in adults. Thus infants may acquire cow's milk allergy during their first year of life. While milk antigen specific IgE may cause allergy in susceptible subjects, there is some evidence indicating that milk antigen specific IgG may play some role in chronic disease development. The puropose of this study was to determine the antigenicity of cow's milk proteins in two animal models and to recommend the more sensitivie one, as an evaluation tool, to assess the antigenicity of a poteintial hypoallergenic formula. A crude extract of cow's milk was injected either to young male rabbits or BALB/C mice in four doses. Pure standard proteins of cow's milk were also injected to separate groups of animals to use their anti sera in later stages. The polyclonal pooled serum was then used to evaluate the antigenicity of the extract by indirect enzyme-linked immunossorbeni assay (LEISA. and Western blotting. Both the rabbit and BALB/C murine mode! demonstrated strong ELISA titres against casein and BSA proteins. However, the rabbit model also had a high antibody response against beta-lactoglobulin (/Mg. The lowest antibody response was found against alpha-kictalbumin («-la in both animal models and no response against immunoglobulins (Igs in either model. In Western blotting, rabbit antiserum showed four bands («-la, /Mg, caseins and BSA compared to two bands (caseins and BSA for mouse antiserum. Considering the allergenicity of these proteins in genetically prone subjects, it may be wise to exclude food sources of caseins as well as major whey proteins (BSA, from the diet of infants with a family history of atopy during the first year of life. The rabbit hyperimmunization model was more sensitive than the murine mode! in detecting antibodies against milk proteins. Thus, the rabbii model should be employed when

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

    Science.gov (United States)

    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.

  9. Effects of different sutures on fibrosis and wound healing in a rabbit model of corneal wounds.

    Science.gov (United States)

    Li, Ying; Chen, Hui J; Zhang, Hua; Wu, Jian G; Hu, Yun T; Ma, Zhi Z

    2016-11-01

    The aim of the study was to investigate wound healing and scar formation in rabbit corneal lamellar wounds repaired with simple interrupted sutures (SIS) or horizontal mattress sutures (HMS). Two parallel 'I'-shaped lamellar cornea wounds were created in one eye of 40 white New Zealand rabbits, while 5 uninjured rabbits were sacrificed to serve as normal controls. One side of the wounds, in the test rabbits, was closed with SIS, while the other side was treated with HMS. Ten days later, the stitches were removed under anesthesia. The animals were sacrificed on days 14 and 21, and months 3 and 6 after the suturing surgery, and corneal samples were subjected to histological and immunofluorescent studies: α-smooth muscle actin (α-SMA) and vimentin were used to detect myofibroblasts and fibroblasts, respectively, and collagen type I and III was used to detect extracellular matrix (ECM) deposition. Relevant mRNA levels were assessed by quantitative polymerase chain reaction (qPCR) to elucidate the differences in wound healing and formation of fibrosis. Macroscopic and hematoxylin and eosin staining observations showed that the two sides of the wounds developed the most prominent fibrotic tissue on day 21. The immunofluorescence and qPCR results showed that HMS wounds produced increased α-SMA, vimentin and collagen type III compared to the SIS wounds on day 14 or 21. The collagen type I expression showed no distinctive difference in SIS and HMS wounds. In conclusion, corneal lamellar wounds treated with SIS developed less fibrotic-related proteins and related mRNA in the early stages of wound healing than wounds treated with HMS. Although differences were not distinct after 3 months, the results of the present study suggest a benefit in choosing SIS over HMS, as at least the initial fibrotic process seems more benign with SIS. Corneal wounds should be carefully sutured, ensuring the tissue is well aligned.

  10. Solution structure and dynamics of the I214V mutant of the rabbit prion protein.

    Directory of Open Access Journals (Sweden)

    Yi Wen

    Full Text Available BACKGROUND: The conformational conversion of the host-derived cellular prion protein (PrP(C into the disease-associated scrapie isoform (PrP(Sc is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs. Various single-point mutations in PrP(Cs could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the differences between the wild-type rabbit PrP(C (RaPrP(C and various mutants would be of great help to understand the ability of RaPrP(C to be resistant to TSE agents. METHODOLOGY/PRINCIPAL FINDINGS: We determined the solution structure of the I214V mutant of RaPrP(C(91-228 and detected the backbone dynamics of its structured C-terminal domain (121-228. The I214V mutant displays a visible shift of surface charge distribution that may have a potential effect on the binding specificity and affinity with other chaperones. The number of hydrogen bonds declines dramatically. Urea-induced transition experiments reveal an obvious decrease in the conformational stability. Furthermore, the NMR dynamics analysis discloses a significant increase in the backbone flexibility on the pico- to nanosecond time scale, indicative of lower energy barrier for structural rearrangement. CONCLUSIONS/SIGNIFICANCE: Our results suggest that both the surface charge distribution and the intrinsic backbone flexibility greatly contribute to species barriers for the transmission of TSEs, and thereby provide valuable hints for understanding the inability of the conformational conversion for RaPrP(C.

  11. Osteogenesis and mineralization in a rabbit mandibular distraction osteogenesis model is promoted by the human LMP-1 gene.

    Science.gov (United States)

    Jiang, Xiaowen; Chen, Yanzhe; Fan, Xiaosheng; Zhang, Hao; Kun, Lu

    2015-04-01

    To observe the effects of LIM mineralization protein-1 (LMP-1) on bone regeneration in the distraction zone based on gene transduction, 36 New Zealand white rabbits underwent mandibular lengthening with a distraction rate of 2 mm/day. The animals were then randomly divided into group A and group B (n = 18, each). At the end of the distraction, Ad5-EGFP viruses and Ad5-LMP-1/EGFP viruses were injected into the distraction gaps in groups A and B, respectively. Seven days later, five randomly selected animals from each group were sacrificed to evaluate the survival of the virus. Four and 8 weeks after distraction osteogenesis (DO), six samples randomly selected from each group underwent CT scanning and dual energy X-ray absorptiometry detection. Eight weeks after DO, the rabbits were sacrificed, and the distracted mandibles were harvested. Six animals from each group processed for radiography, micro-CT, histology, and the rest samples were taken three-point bend testing. Using this model, better bone formation and mineralization in the distracted callus were observed in group B when compared with those in group A. The results suggest local transduction with LMP-1 gene promotes osteogenesis and mineralization in DO.

  12. Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Martyn Harvey

    2011-01-01

    Full Text Available Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING, and more recently intravenous lipid emulsion (ILE, have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity. Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group, or 10 mL/kg 20% Intralipid (ILE group. Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure was greatest in the ING group at 60 minutes (P<.05. A trend toward greater heart rate was observed in the ING group (P=.06. No difference was observed in survival between groups (4/5 ING versus 2/5 ILE; P=.524. Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2012-01-01

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

  15. Regeneration of whole meniscus using meniscal cells and polymer scaffolds in a rabbit total meniscectomy model.

    Science.gov (United States)

    Kang, Sun-Woong; Son, Sun-Mi; Lee, Jae-Sun; Lee, Eung-Seok; Lee, Kwon-Yong; Park, Sang-Guk; Park, Jung-Ho; Kim, Byung-Soo

    2006-09-01

    The current treatments of meniscal lesion in knee joint are not perfect to prevent adverse effects of meniscus injury. Tissue engineering of meniscus using meniscal cells and polymer scaffolds could be an alternative option to treat meniscus injury. This study reports on the regeneration of whole medial meniscus in a rabbit total meniscectomy model using the tissue engineering technique. Biodegradable scaffolds in a meniscal shape were fabricated from polyglycolic acid (PGA) fiber meshes that were mechanically reinforced by bonding PGA fibers at cross points with 75:25 poly(lactic-co-glycolic acid). The compressive modulus of the bonded PGA scaffold was 28-fold higher than that of nonbonded scaffold. Allogeneic meniscal cells were isolated from rabbit meniscus biopsy and cultured in vitro. The expanded meniscal cells were seeded onto the polymer scaffolds, cultured in vitro for 1 week, and transplanted to rabbit knee joints from which medial menisci were removed. Ten or 36 weeks after transplantation, the implants formed neomenisci with the original scaffold shape maintained approximately. Hematoxylin and eosin staining of the sections of the neomenisci at 6 and 10 weeks revealed the regeneration of fibrocartilage. Safranin-O staining showed that abundant proteoglycan was present in the neomenisci at 10 weeks. Masson's trichrome staining indicated the presence of collagen. Immunohistochemical analysis showed that the presence of type I and II collagen in neomenisci at 10 weeks was similar to that of normal meniscal tissue. Biochemical and biomechanical analyses of the tissue-engineered menisci at 36 weeks were performed to determine the quality of the tissue-engineered menisci. Tissue-engineered meniscus showed differences in collagen content and aggregate modulus in comparison with native meniscus. This study demonstrates, for the first time, the feasibility of regenerating whole meniscal cartilage in a rabbit total meniscectomy model using the tissue engineering

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Establishment of a blunt impact-induced brain injury model in rabbits

    Institute of Scientific and Technical Information of China (English)

    LI Kui; CAO Yun-xing; YANG Yong-qiang; YIN Zhi-yong; ZHAO Hui; WANG Li-jun

    2012-01-01

    Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine.Methods:Twenty-four New Zealand white rabbits were randomly divided into control group (n=4),minor injury group (n=10) and severe injury group (n=10).Based on the BIM- Ⅱ Horizontal Bio-impact Machine,self-designed iron bar was used to produce blunt brain injury.Two rabbits from each injury group were randomly selected to monitor the change ofintracranial pressure (ICP) during the impacting process by pressure microsensors.Six hours after injury,all the rabbits were dissected to observe the injury morphology and underwent routine pathological examination.Results: Varying degrees of nervous system positive signs were observed in all the injured rabbits.Within 6 hours,the mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group.Morphological changes consisted of different levels of scalp hematoma,skull fracture,epiduraI hematoma,subdural hematoma,subarachnoid hemorrhage and brain injury.At the moment of hitting,the ICP was greater in severe injury group than in mild injury group; and within the same group,the impact side showed positive pressure while the opposite side showed negative pressure.Conclusions:Under the rigidly-controlled experimental condition,this animal model has a good reproducibility and stable results.Meanwhile,it is able to simulate the morphology of iron strike-induced injury,thus can be used to study the mechanism of blunt head injury in forensic medicine.

  18. Characterization of rabbit ileal receptors for Clostridium difficile toxin A. Evidence for a receptor-coupled G protein

    Energy Technology Data Exchange (ETDEWEB)

    Pothoulakis, C.; LaMont, J.T.; Eglow, R.; Gao, N.; Rubins, J.B.; Theoharides, T.C.; Dickey, B.F. (Boston Univ. School of Medicine, MA (USA))

    1991-07-01

    The purpose of this study was to characterize the surface receptor for toxin A, the enterotoxin from Clostridium difficile, on rabbit intestinal brush borders (BB) and on rat basophilic leukemia (RBL) cells. Purified toxin A was radiolabeled using a modified Bolton-Hunter method to sp act 2 microCi/micrograms, with retention of full biologic activity. 3H-Toxin A bound specifically to a single class of receptors on rabbit BB and on RBL cells with dissociation constants of 5.4 x 10(-8) and 3.5 x 10(-8) M, respectively. RBL cells were highly sensitive to toxin A (cell rounding) and had 180,000 specific binding sites per cell, whereas IMR-90 fibroblasts were far less sensitive to toxin A and lacked detectable specific binding sites. Exposure of BB to trypsin or chymotrypsin significantly reduced 3H-toxin A specific binding. Preincubation of BB with Bandeirea simplicifolia (BS-1) lectin also reduced specific binding, and CHAPS-solubilized receptors could be immobilized with WGA-agarose. The addition of 100 nM toxin A accelerated the association of 35S-GTP gamma S with rabbit ileal BB, and preincubation of BB with the GTP analogues GTP gamma S or Gpp(NH)p, significantly reduced 3H-toxin A specific binding. Our data indicate that the membrane receptor for toxin A is a galactose and N-acetyl-glucosamine-containing glycoprotein which appears to be coupled to a G protein.

  19. Implanting hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 and hyaluronic acid into distal femoral metaphysis of rabbits

    Institute of Scientific and Technical Information of China (English)

    PENG Lei; BIAN Wei-guo; LIANG Fang-hui; XU Hua-zi

    2008-01-01

    Objective: To assess the osseointegration capability of hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 (BMP-2) and hyaluronic acid to repair defects in the distal femur metaphysis in rabbits. Methods: Porous titanium implants were made by sintering titanium powder at high temperature, which were coated with hydroxyapatite by alkali and heat treatment and with BMP-2 combined with bone regeneration materials. And hyaluronic acid was further used as delivery system to prolong the effect of BMP-2. The implants were inserted into the metaphysis of the distal femur of rabbits. The animals were killed at 6, 12 and 24 weeks to accomplish histological and biomechanical analyses. Results: According to the result of histological analysis, the osseointegration in BMP-2 group was better than that of the HA-coated porous titanium group. In push-out test, all the samples had bigger shear stress as time passed by. There was statistical difference between the two groups in 6 and 12 weeks but not in 24 weeks. Conclusion: Hydroxyapatite-coated porous titanium with BMP-2 and hyaluronic acid has a good effect in repairing defects of distal fumur in rabbits, which is a fine biotechnology for future clinical application.

  20. A Novel Minimally Invasive Technique to Create a Rabbit VX2 Lung Tumor Model for Nano-Sized Image Contrast and Interventional Studies

    OpenAIRE

    Takashi Anayama; Takahiro Nakajima; Michael Dunne; Jinzi Zheng; Christine Allen; Brandon Driscoll; Douglass Vines; Shaf Keshavjee; David Jaffray; Kazuhiro Yasufuku

    2013-01-01

    BACKGROUND: The rabbit VX2 lung cancer model is a large animal model useful for preclinical lung cancer imaging and interventional studies. However, previously reported models had issues in terms of invasiveness of tumor inoculation, control of tumor aggressiveness and incidence of complications. PURPOSE: We aimed to develop a minimally invasive rabbit VX2 lung cancer model suitable for imaging and transbronchial interventional studies. METHODS: New Zealand white rabbits and VX2 tumors were u...

  1. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    OpenAIRE

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck f...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Yue Song

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

  4. Evaluation of arterial impairment after experimental gelatin sponge embolization in a rabbit renal model

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Suk; Lee, Hae Gi; Chun, Ho Jong; Choi, Byung Gil; Choi, Yeong Jin [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-02-15

    Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle actin immunohistochemical stained sections. Gelatin sponge particles were mainly observed in the segmental and interlobar arteries. Transmural inflammation of the embolized arterial wall and mild thickening of the media were observed 1 week after embolization. Resorption of the gelatin sponge and organization of thrombus accompanied by foreign body reactions, were observed from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group showed vessel lumens filled mostly with organized thrombi, resulting in severe stenosis. Additionally, vessels showed a thickened intima that contained migrating smooth muscle cells and accompanying interruption of the internal elastic lamina. The migrating smooth muscle cells were distributed around the recanalized arterial lumen. Gelatin sponge embolization may induce arterial stenosis by causing organized thrombus and intimal hyperplasia, which consists of migrating smooth muscle cells and intimal collagen deposits.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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

  8. Modeling Mercury in Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeremy C [ORNL; Parks, Jerry M [ORNL

    2016-01-01

    Mercury (Hg) is a naturally occurring element that is released into the biosphere both by natural processes and anthropogenic activities. Although its reduced, elemental form Hg(0) is relatively non-toxic, other forms such as Hg2+ and, in particular, its methylated form, methylmercury, are toxic, with deleterious effects on both ecosystems and humans. Microorganisms play important roles in the transformation of mercury in the environment. Inorganic Hg2+ can be methylated by certain bacteria and archaea to form methylmercury. Conversely, bacteria also demethylate methylmercury and reduce Hg2+ to relatively inert Hg(0). Transformations and toxicity occur as a result of mercury interacting with various proteins. Clearly, then, understanding the toxic effects of mercury and its cycling in the environment requires characterization of these interactions. Computational approaches are ideally suited to studies of mercury in proteins because they can provide a detailed picture and circumvent issues associated with toxicity. Here we describe computational methods for investigating and characterizing how mercury binds to proteins, how inter- and intra-protein transfer of mercury is orchestrated in biological systems, and how chemical reactions in proteins transform the metal. We describe quantum chemical analyses of aqueous Hg(II), which reveal critical factors that determine ligand binding propensities. We then provide a perspective on how we used chemical reasoning to discover how microorganisms methylate mercury. We also highlight our combined computational and experimental studies of the proteins and enzymes of the mer operon, a suite of genes that confers mercury resistance in many bacteria. Lastly, we place work on mercury in proteins in the context of what is needed for a comprehensive multi-scale model of environmental mercury cycling.

  9. Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Jeff Min

    Full Text Available CLINICAL RELEVANCE: Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS. Safer, more targeted, anti-fibrosis agents are sought. OBJECTIVES: The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections. METHODS: Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS, or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings. RESULTS: Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018. No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749. Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity. CONCLUSIONS: Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fichorova, Raina N., E-mail: rfichorova@rics.bwh.harvard.edu [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chandra, Neelima; Doncel, Gustavo F. [CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA (United States)

    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

  11. Adenosine monophosphate-activated protein kinase activation and suppression of inflammatory response by cell stretching in rabbit synovial fibroblasts.

    Science.gov (United States)

    Kunanusornchai, Wanlop; Muanprasat, Chatchai; Chatsudthipong, Varanuj

    2016-12-01

    Joint mobilization is known to be beneficial in osteoarthritis (OA) patients. This study aimed to investigate the effect of stretching on adenosine monophosphate-activated protein kinase (AMPK) activity and its role in modulating inflammation in rabbit synovial fibroblasts. Uniaxial stretching of isolated rabbit synovial fibroblasts for ten min was performed. Stretching-induced AMPK activation, its underlying mechanism, and its anti-inflammatory effect were investigated using Western blot. Static stretching at 20 % of initial length resulted in AMPK activation characterized by expression of phosphorylated AMPK and phosphorylated acetyl-Co A carboxylase. AMP-activated protein kinase phosphorylation peaked 1 h after stretching and declined toward resting activity. Using cell viability assays, static stretching did not appear to cause cellular damage. Activation of AMPK involves Ca(2+) influx via a mechanosensitive L-type Ca(2+) channel, which subsequently raises intracellular Ca(2+) and activates AMPK via Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ). Interestingly, stretching suppressed TNFα-induced expression of COX-2, iNOS, and phosphorylated NF-κB. These effects were prevented by pretreatment with compound C, an AMPK inhibitor. These results suggest that mechanical stretching suppressed inflammatory responses in synovial fibroblasts via a L-type Ca(2+)-channel-CaMKKβ-AMPK-dependent pathway which may underlie joint mobilization's ability to alleviate OA symptoms.

  12. Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines

    DEFF Research Database (Denmark)

    Case, R M; Conigrave, A D; Novak, I

    1980-01-01

    1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate.2. During perfusion with solutions containing acetylcholine, the gland secretes vigor...

  13. Distribution of endotracheally instilled surfactant protein SP-C in lung-lavaged rabbits.

    NARCIS (Netherlands)

    Bambang Oetomo, Sidarto; de Leij, Louis; Curstedt, T; ter Haar, J G; Schoots, Coenraad; Wildevuur, Charles; Okken, Albert

    1991-01-01

    In lung-lavaged surfactant-deficient rabbits (n = 6) requiring artificial ventilation, porcine surfactant was instilled endotracheally. This resulted in improvement of lung function so that the animals could be weaned off artificial ventilation. The animals were killed 4 1/2 h after surfactant admin

  14. Effects of Yiqi Tongyang on HCN4 Protein Phosphorylation in Damaged Rabbit Sinoatrial Node Cells

    Directory of Open Access Journals (Sweden)

    Jinfeng Liu

    2016-01-01

    Full Text Available The hyperpolarization-activated cyclic nucleotide-gated cation channel (If is closely associated with sinoatrial node pacing function. The present study aimed to investigate the molecular mechanisms involved in pacing function improvements of damaged sinoatrial node cells and the consequent treatment effects on sick sinus syndrome (SSS after the use of Yiqi Tongyang. HCN4 channel protein expression and phosphorylation were measured by immunoblotting and fluorescent quantitation. After ischemia-reperfusion injury (model group, the HCN4 protein and the optical density (OD of the phosphorylated HCN4 protein as well as intracellular PKA activity in the sinoatrial node cells decreased significantly. However, the OD values and PKA activity increased to different degrees after treatment with serum containing different doses of Yiqi Tongyang; in contrast, no significant improvement was seen in the control group compared to the model group. These findings demonstrated that the use of the traditional Chinese medicine Yiqi Tongyang could increase HCN4 protein expression and phosphorylation as well as PKA activity within sinoatrial node cells damaged by ischemia-reperfusion. The HCN4 protein is involved in the If-related ion channel. Here, we speculated that these effects could be associated with upregulation of HCN4 protein phosphorylation, which consequently improved cell automaticity, increased heart rate, and had treatment effects on SSS.

  15. Effects of Yiqi Tongyang on HCN4 Protein Phosphorylation in Damaged Rabbit Sinoatrial Node Cells.

    Science.gov (United States)

    Liu, Jinfeng; Liu, Ruxiu; Peng, Jie; Wang, Yanli

    2016-01-01

    The hyperpolarization-activated cyclic nucleotide-gated cation channel (I f ) is closely associated with sinoatrial node pacing function. The present study aimed to investigate the molecular mechanisms involved in pacing function improvements of damaged sinoatrial node cells and the consequent treatment effects on sick sinus syndrome (SSS) after the use of Yiqi Tongyang. HCN4 channel protein expression and phosphorylation were measured by immunoblotting and fluorescent quantitation. After ischemia-reperfusion injury (model group), the HCN4 protein and the optical density (OD) of the phosphorylated HCN4 protein as well as intracellular PKA activity in the sinoatrial node cells decreased significantly. However, the OD values and PKA activity increased to different degrees after treatment with serum containing different doses of Yiqi Tongyang; in contrast, no significant improvement was seen in the control group compared to the model group. These findings demonstrated that the use of the traditional Chinese medicine Yiqi Tongyang could increase HCN4 protein expression and phosphorylation as well as PKA activity within sinoatrial node cells damaged by ischemia-reperfusion. The HCN4 protein is involved in the I f -related ion channel. Here, we speculated that these effects could be associated with upregulation of HCN4 protein phosphorylation, which consequently improved cell automaticity, increased heart rate, and had treatment effects on SSS.

  16. Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ghribi Othman

    2008-04-01

    Full Text Available Abstract High levels of serum cholesterol and disruptions of the blood brain barrier (BBB have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.

  17. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    Science.gov (United States)

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge.

  18. Investigation of carbohydrate and protein metabolism in the digestive organs of the rabbit under the combined influence of vibration, acceleration and irradiation

    Science.gov (United States)

    Yuy, R. I.

    1975-01-01

    During spaceflight, the organism is subjected to the influence of various extremal factors such as acceleration, vibration, irradiation, etc. The study of the influence of these factors on metabolism, especially carbohydrate and protein metabolism, in young rabbits is of great significance in simulation experiments. Dynamic factors and irradiation, depending on dose and duration, lead to reduced RNA and protein metabolism.

  19. Circadian nursing induces PER1 protein in neuroendocrine tyrosine hydroxylase neurones in the rabbit doe.

    Science.gov (United States)

    Meza, E; Waliszewski, S M; Caba, M

    2011-06-01

    Rabbit does nurse their pups once a day with circadian periodicity and pups ingest up to 35% of their body weight in milk in < 5 min. In the doe, there is a massive release of prolactin. We hypothesised that periodic suckling synchronises dopaminergic populations that control prolactin secretion. We explored this by immunohistochemical colocalisation of PER1 protein, the product of the clock gene Per1 on tyrosine hydroxylase (TH) cells in three dopaminergic populations: tuberoinfundibular dopaminergic (TIDA), periventricular hypophyseal dopaminergic (PHDA) and incertohypothalamic dopaminergic (IHDA) cells. PER1/TH colocalisation was explored every 4 h through a complete 24-h cycle at postpartum day 7 in does that nursed their pups either at 10.00 h (ZT03) or at 02.00 h (ZT19; ZT0 = 07.00 h, time of lights on). Nonpregnant, nonlactating females were used as controls. In control females, there was a rhythm of PER1 that peaks at ZT15. By contrast, in nursed does, the PER1 peak shifted in parallel to scheduled nursing in TIDA and PHDA cells but not in IHDA cells, which are not related to the control of prolactin. Next, we determined that the absence of suckling for 48 h significantly decreases the number of PER1/TH colocalised cells in PHDA but not TIDA cells. Locomotor behaviour in control subjects was maximal at around the time of lights on but, in nursed females, shifted at around the time of scheduled nursing. Finally, in the suprachiasmatic nucleus, there is a maximal expression of PER1 at ZT11 in the three groups. However, this maximal expression was significantly lower in the nursed groups in relation to the control group and in the groups deprived of nursing for 48 h. We conclude that suckling synchronises dopaminergic cells related to the control of prolactin and appears to be a nonphotic stimulus for the suprachiasmatic nucleus. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  20. Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus.

    Science.gov (United States)

    Hu, Jiafen; Budgeon, Lynn R; Cladel, Nancy M; Culp, Timothy D; Balogh, Karla K; Christensen, Neil D

    2007-12-01

    Shope papillomavirus or cottontail rabbit papillomavirus (CRPV) is one of the first small DNA tumour viruses to be characterized. Although the natural host for CRPV is the cottontail rabbit (Sylvilagus floridanus), CRPV can infect domestic laboratory rabbits (Oryctolagus cuniculus) and induce tumour outgrowth and cancer development. In previous studies, investigators attempted to passage CRPV in domestic rabbits, but achieved very limited success, leading to the suggestion that CRPV infection in domestic rabbits was abortive. The persistence of specific anti-L1 antibody in sera from rabbits infected with either virus or viral DNA led us to revisit the questions as to whether L1 and infectious CRPV can be produced in domestic rabbit tissues. We detected various levels of L1 protein in most papillomas from CRPV-infected rabbits using recently developed monoclonal antibodies. Sensitive in vitro infectivity assays additionally confirmed that extracts from these papillomas were infectious. These studies demonstrated that the CRPV/New Zealand White rabbit model could be used as an in vivo model to study natural virus infection and viral life cycle of CRPV and not be limited to studies on abortive infections.

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

    Science.gov (United States)

    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.

  2. Multiscale modeling of proteins.

    Science.gov (United States)

    Tozzini, Valentina

    2010-02-16

    The activity within a living cell is based on a complex network of interactions among biomolecules, exchanging information and energy through biochemical processes. These events occur on different scales, from the nano- to the macroscale, spanning about 10 orders of magnitude in the space domain and 15 orders of magnitude in the time domain. Consequently, many different modeling techniques, each proper for a particular time or space scale, are commonly used. In addition, a single process often spans more than a single time or space scale. Thus, the necessity arises for combining the modeling techniques in multiscale approaches. In this Account, I first review the different modeling methods for bio-systems, from quantum mechanics to the coarse-grained and continuum-like descriptions, passing through the atomistic force field simulations. Special attention is devoted to their combination in different possible multiscale approaches and to the questions and problems related to their coherent matching in the space and time domains. These aspects are often considered secondary, but in fact, they have primary relevance when the aim is the coherent and complete description of bioprocesses. Subsequently, applications are illustrated by means of two paradigmatic examples: (i) the green fluorescent protein (GFP) family and (ii) the proteins involved in the human immunodeficiency virus (HIV) replication cycle. The GFPs are currently one of the most frequently used markers for monitoring protein trafficking within living cells; nanobiotechnology and cell biology strongly rely on their use in fluorescence microscopy techniques. A detailed knowledge of the actions of the virus-specific enzymes of HIV (specifically HIV protease and integrase) is necessary to study novel therapeutic strategies against this disease. Thus, the insight accumulated over years of intense study is an excellent framework for this Account. The foremost relevance of these two biomolecular systems was

  3. Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

    Directory of Open Access Journals (Sweden)

    M. Skaff

    2012-02-01

    Full Text Available OBJECTIVE: The aim of the study was to develop a new durable animal model (using rabbits for anatomical-functional evaluation of urethral sphincter deficiency. MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two animals underwent urethrolysis and 8 animals received sham operation. Before and at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed cystometry and leak point pressure (LPP evaluation with different bladder distension volumes (10, 20, 30 mL. In each time point, 10 animals (8 from the study group and 2 from the sham group were sacrificed to harvest the bladder and urethra. The samples were evaluated by H&E and Masson's Trichrome to determine urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks after urethrolysis, it was observed a significant decrease in LPP regardless the bladder volume (from 33.7 ± 6.6 to 12.8 ± 2.2 cmH2O. The histological analysis evidenced a decrease of 22% in smooth muscle density with a proportional increase in the collagen, vessels and elastin density (p < 0.01. CONCLUSIONS: Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits, with significant decrease in LPP associated with decrease of smooth muscle fibers and increase of collagen density. This animal model can be used to test autologous cell therapy for stress urinary incontinence treatment.

  4. Evaluation of the Mtb72F Polyprotein Vaccine in a Rabbit Model of Tuberculous Meningitis

    OpenAIRE

    Tsenova, Liana; Harbacheuski, Ryhor; Moreira, Andre L.; Ellison, Evette; Dalemans, Wilfried; Alderson, Mark R.; Mathema, Barun; Reed, Steven G.; Skeiky, Yasir A. W.; Kaplan, Gilla

    2006-01-01

    Using a rabbit model of tuberculous meningitis, we evaluated the protective efficacy of vaccination with the recombinant polyprotein Mtb72F, which is formulated in two alternative adjuvants, AS02A and AS01B, and compared this to vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) alone or as a BCG prime/Mtb72F-boost regimen. Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS...

  5. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    Science.gov (United States)

    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.

  6. The beta-adrenergic blocker carvedilol restores L-type calcium current in a myocardial infarction model of rabbit

    Institute of Scientific and Technical Information of China (English)

    LI Xia; HUANG Cong-xin; JIANG Hong; CAO Feng; WANG Teng

    2005-01-01

    Background Carvedilol, an antagonist of α1- and β-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.Methods After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot. Results The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33±0.45, n=25) compared to sham myocytes (6.52±0.21, n=20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91±0.39, n=20, P<0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 μmol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed. Conclusions The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.

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

    Science.gov (United States)

    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.

  8. Panton-Valentine leukocidin does play a role in the early stage of Staphylococcus aureus skin infections: a rabbit model.

    Directory of Open Access Journals (Sweden)

    Urszula Lipinska

    Full Text Available Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL, the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils--the major target cells for PVL--are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 10(8 cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections.

  9. A hyperoxic lung injury model in premature rabbits: the influence of different gestational ages and oxygen concentrations.

    Directory of Open Access Journals (Sweden)

    Roberta Munhoz Manzano

    Full Text Available BACKGROUND: Many animal models have been developed to study bronchopulmonary dysplasia (BPD. The preterm rabbit is a low-cost, easy-to-handle model, but it has a high mortality rate in response to the high oxygen concentrations used to induce lung injury. The aim of this study was to compare the mortality rates of two models of hyperoxia-induced lung injury in preterm rabbits. METHODS: Pregnant New Zealand white rabbits were subjected to caesarean section on gestational day 28 or 29 (full term  = 31 days. The premature rabbits in the 28-day gestation group were exposed to room air or FiO₂ ≥95%, and the rabbits in the 29-day gestation group were exposed to room air or FiO₂  = 80% for 11 days. The mean linear intercept (Lm, internal surface area (ISA, number of alveoli, septal thickness and proportion of elastic and collagen fibers were quantified. RESULTS: The survival rates in the 29-day groups were improved compared with the 28-day groups. Hyperoxia impaired the normal development of the lung, as demonstrated by an increase in the Lm, the septal thickness and the proportion of elastic fibers. Hyperoxia also decreased the ISA, the number of alveoli and the proportion of collagen fibers in the 28-day oxygen-exposed group compared with the control 28-day group. A reduced number of alveoli was found in the 29-day oxygen exposed animals compared with the control 29-day group. CONCLUSIONS: The 29-day preterm rabbits had a reduced mortality rate compared with the 28-day preterm rabbits and maintained a reduction in the alveoli number, which is comparable to BPD in humans.

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

    Science.gov (United States)

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

    2011-03-01

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

  11. Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Tao Gu; Cai-Xia Li; Yan Feng; Qian Wang; Chun-Hai Li; Chuan-Fu Li

    2007-01-01

    AIM: To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.METHODS: VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only,group B receiving combined Ad-p53 therapy and transarterial embolization (lipiodol), group C receiving transarterial chemoembolization (lipiodol + mitomycin C),control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13).Interventional procedure was applied (d 14).Tumor volume (V2) was assessed by MRT (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS: Compared with control group ((-x) = 3.14± 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P < 0.05). A slight difference was found between group A ((-x) =2.35 ±0.59) and group B ((-x) = 1.75 ± 0.28) (P = 0.048). Nostatistically significant difference was observed between group B and group C ((-x) = 2.00 ± 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P < 0.05).Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION: Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.

  12. Evaluation of the rabbit as an experimental model for human uterine synechia

    Directory of Open Access Journals (Sweden)

    Mohamed Khrouf

    2012-01-01

    Full Text Available Context: Pathogenesis of uterine synechia remains unsolved, the causal relationship between synechia and infertility is not clearly established. Aims: To evaluate the rabbit as an experimental model for Asherman′s syndrome using the endometrial curettage as trigger mechanism then to evaluate its impact on fertility. Settings and Design: Experimental study Materials and Methods: 13 female rabbits. All submitted traumatic endometrial curettage. Animals of Group 1 (n = 7 were sacrificed at various times following surgery (day 7, 15 and 30, animals of Group 2 (n = 6 were bred and sacrificed during pregnancy. Main outcome were synechia occurring, number of implanted fetus, lumen surface/ global horn perimeter ratio (LS-GHP ratio and epithelium thickness. Statistical Analysis: Means were compared using Student ′t′ test (P < 0.05 was considered significant. Number of implantation sites of two horns were compared with the Wilcoxon test. Results: No synechia have been observed. Examinations at Day 7, 15 and 30 demonstrate a complete regeneration of endometrium. We observed a significant diminished LS-GHP ratio at day 7 (0.042 ± 0.004 vs 0.074 ± 0.002 mm; P = 0.013 with a higher simple columnar epithelium compared to control (16.6 ± 3.39 vs 10.98 ± 1.7; P = 0.001. We observed a diminished ovum implantation in traumatized horns, even if it was not statistically significant. Conclusion: Even if no intrauterine adhesion were observed, this model represents a pathogenesis condition in the rabbit similar to intrauterine adhesions observed in the human with negative impact on implantation.

  13. The Ultrasonographic Findings of Trigger Points of Myofascial Pain Syndrome in a Rabbit Model

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Kyung Mi; Park, Seog Hee [Catholic University of Korea, Kangnam St. Mary' s Hospital, Seoul (Korea, Republic of); Lee, Sang Heon; Kim, Joo Hyun; Kim, Han Kyum [Korea University College of Medicine, Seoul (Korea, Republic of)

    2005-03-15

    Myofascial pain syndrome (MPS) is a common cause of musculoskeletal pain. Myofascial trigger points (MTrPs) have been repeatedly described by numerous authors. However, there have been few studies in which their existence and behavior was supported and their location confirmed. The purpose of this study was to determine whether diagnostic ultrasonography is an objective diagnostic tool which is able to significantly identify or detect the soft tissue changes in the region of clinically identified active MTrPs by using a rabbit experimental model. Ten MPS model rabbits were used in this study. We made an MPS animal model by causing the rabbits to overuse one leg for 3 weeks by cutting the contralateral L4 spinal nerve root. We compared the ultrasonographic findings of the taut band at pre-OP with those at post-OP during the consecutive three week period. To find the taut bands of the muscle, after skin exposure, the muscles were gently rubbed or pinched with the thumb and index finger on the two opposing surfaces of the muscle across the direction of the fibers. Then, the muscle was held in the same way, but with a 5-8 MHz stick probe being used in place of the thumb. After the palpation of various muscles, we selected the hardest and largest myofascial trigger nodule, in order to observe the ultrasonographic and power Doppler findings of the MPS. The size, shape, echogenecity and vascularity of the MTrPs were observed. The analysis of the results of the ultrasonography revealed that all MTrPs have a hyperechoic area. The mean thickness of the hyperechoic lesion in the biceps was 0.96{+-}0.14 cm in the MPS site (at pre-OP?), and 0.49{+-}0.12 cm at post-OP 3weeks (p < 0.01). The hyperechoic lesions in all of the studied biceps femoris of the rabbits were observed by high resolution ultrasonography. No definitively decreased vascularity was observed within the hyperechoic area by power Doppler imaging. Until now, there has been no objective method for the diagnosis of

  14. Experimental pleural empyema model in rabbits: Why, how and what are the next steps

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    Cvijanović Vlado

    2014-01-01

    Full Text Available Bacgraund/Aim. The use of new therapeutic methods to prevent development of fibrothorax as the final complication of the human pleural infections requires research with experimental animals. The aim of this study was to standardize the procedures for the establishment of our own experimental model of empyema in rabbits, since it should be able to offer similar conditions found in human pleural infections. Methods. This experiment included 15 chinchilla rabbits, weighing from 2.3 to 2.8 kg. There were 12 rabbits in the experimental group, while 3 rabbits formed the control group. On the first day, we administered 0.4-0.5 mL of turpentine in the right pleural space of the rabbits from the experimental group in order to provoke sterile exudative pleurisy. After 24 h we injected 1 mL of Staphylococcus aureus and 1 mL of Escherichia coli bacteria in the same concentration of 4.5 x 108 bacteria/mL. Thoracocentesis for the pleural fluid analysis was performed 24, 48, 72, and 96 h after bacteria instillation. In these pleural samples we estimated the number of leucocytes and the values of lactate dehydrogenase (LDH, glucose and pH in pleural fluid, as well as the presence of bacteria. We did not protect the animals with antibiotics, and on the day 7 of the experiment they were sacrificed with the lethal dose of barbiturate (iv. The lung from the empyemic side of all experimental animals and the lung of one control animal were histopathologically examined. Results. A total of 4 animals had a small amount of clear pleural fluids or there was no fluid obtained with thoracocentesis 24 and 48 h after the bacteria instillation. after the bacteria instillation. In the remaining 8 rabbits 24 h after bacteria administration the mean values (± SD of the parameters monitored were as follows: Le 34.75 ± 6.13 x 109/L, LDH 17,000 ± 4,69 U/L, glucose 1.23 ± 0.45 mmol/L, and pH 6.975 ± 0.15. The obtained values met the criteria for the evaluation of effusion as

  15. The study of expanded tri-lobed flap in a rabbit model: possible flap model in ear reconstruction?

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    Yüreklý Yakup

    2003-12-01

    Full Text Available Abstract Background Local flaps are widely used in reconstructive surgery. Tri-lobed skin flap is a relatively new flap and there has been no experimental model of this flap. This flap can be used for repair of full thickness defects in the face, ears and alar region. Based on the size of ears in a rabbit, we designed a model of ear reconstruction using expanded tri-lobed flap. Local flaps are more advantageous in that they provide excellent color and texture matching up with those of the face, adequately restore ear contour, place scars in a favorable location and ideally accomplish these goals in a single stage with minimal donor site morbidity. Methods Eight adult New Zealand rabbits were divided into two groups. 50 ml round tissue expander were implanted to four rabbits. After completion of the expansion, a superiorly based tri-lobed flap was elevated and a new ear was created from the superior dorsal skin of each rabbit. Scintigraphy with Technetium-99m pertecnetate was performed to evaluate flap viability. Results Subtotal flap necrosis was seen in all animals in non-expanded group. New ear in dimensions of the original ear was created in expanded group without complication. Perfusion and viability of the flaps were proved by Technetium-99m pertecnetate scintigraphy. Conclusion According to our knowledge this study is the first to demonstrate animal model in tri-lobed flap. Also, our technique is the first application of the trilobed flap to the possible ear reconstruction. We speculated that this flap may be used mastoid based without hair, in human. Also, tri-lobed flap may be an alternative in reconstruction of cylindrical organs such as penis or finger.

  16. The development of an experimental model of contaminated muscle injury in rabbits.

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    Eardley, Will G P; Martin, Kevin R; Taylor, Chris; Kirkman, Emrys; Clasper, Jon C; Watts, Sarah A

    2012-12-01

    Extent of tissue trauma and contamination determine outcome in extremity injury. In contrast to fracture, osteomyelitis, and closed muscle injury studies, there are limited small animal models of extremity muscle trauma and contamination. To address this we developed a model of contaminated muscle injury in rabbits. Twenty-eight anesthetized New Zealand White rabbits underwent open controlled injury of the flexor carpi ulnaris (FCU). Twenty-two animals had subsequent contamination of the injured muscle with Staphylococcus aureus. All animals were sacrificed at 48 hours and the level of muscle injury and contamination determined by quantitative histological and microbiological analysis. A 1-kg mass dropped 300 mm onto the mobilized FCU resulted in localized necrosis of the muscle belly. Delivery of a mean challenge of 3.71 × 10(6) cfu/100 µL S aureus by droplet spread onto the injured muscle produced a muscle contamination of 8.79 × 10(6) cfu/g at 48 hours. Ipsilateral axillary lymph nodes demonstrated clinically significant activation. All animals had normal body temperature and hematological parameters throughout and blood and urinalysis culture at autopsy were negative for organisms. This model allows reproducible muscle injury and contamination with the organism ubiquitous to extremity wound infection at a level sufficient to allow quantitative assessment of subsequent wound care interventions without incurring systemic involvement.

  17. Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation

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    Paixão Fabio B

    2008-01-01

    Full Text Available Abstract Background Animal models of fracture consolidation are fundamental for the understanding of the biological process of bone repair in humans, but histological studies are rare and provide only qualitative results. The objective of this article is to present the histomorphometric study of the bone healing process using an experimental model of osteotomy in rabbit fibula without interference of synthesis material. Methods Fifteen rabbits were submitted to fibular osteotomy without any fixation device. Groups of five animals were submitted to pharmacological euthanasia during a period of one (group A, two (group B and four weeks (group C after osteotomy. Histomorphometric evaluation was performed in the histological sections. Results During week one there was intense cellularity (67/field, a large amount of woven bone (75.7% and a small amount of lamellar bone (7.65%. At two weeks there was a decrease in woven bone (41.59% and an increase in lamellar bone (15.16%. At four weeks there was a decrease of cellularity (19.17/field and lamellar bone (55.56% exceeded the quantity of woven bone (31.68%. Conclusion Histomorphometric (quantitative evaluation of the present study was shown to be compatible with bone healing achieved in qualitative experimental models that have been commended in the literature.

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

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    Rania M El Backly

    2015-01-01

    Full Text Available 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 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. Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits

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    Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen

    2016-01-01

    Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839

  20. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

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    Xiang-Ming Fang

    2015-01-01

    Full Text Available Background: To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI for the future investigation of computed tomography perfusion. Methods: A total of 72 New Zealand rabbits were randomly divided into two groups: 36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung; 36 rabbits in the control group were sham-radiated. All rabbits were subsequently sacrificed at 1, 6, 12, 24, 48, 72 h, and 1, 2, 4, 8,1 6, 24 weeks after radiation, and then six specimens were extracted from the upper, middle and lower fields of the bilateral lungs. The pathological changes in these specimens were observed with light and electron microscopy; the expression of tumor necrosis factor-α (TNF-a and transforming growth factor-β1 (TGF-β1 in local lung tissue was detected by immunohistochemistry. Results: (1 Radiation-induced lung injury occurred in all rabbits in the test group. (2 Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation, demonstrated a statistically significant difference between the test and control groups (each P 0.05. At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05, correlating well with the time postradiation (r = 0.99318. Conclusions: A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray, which can simulate the development and evolution of RILI.

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

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    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.

  2. Identification of superficial Candida albicans germ tube antigens in a rabbit model of disseminated candidiasis. A proteomic approach.

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    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.

  3. Feasibility and mortality of airway balloon dilation in a live rabbit model.

    Science.gov (United States)

    Visaya, Jiovani M; Ward, Robert F; Modi, Vikash K

    2014-03-01

    Endoscopic balloon dilation is commonly performed in children with airway stenosis, but guidelines are needed for selecting safe and effective balloon inflation parameters. To determine the feasibility and safety of airway balloon dilation in live rabbits using a range of balloon diameters and pressures. Prospective animal study using 32 adult New Zealand white rabbits with 1-week follow-up performed at an academic animal research facility. Rabbits underwent endoscopic laryngeal balloon dilation with diameters ranging from 6 to 10 mm and pressures of 5 to 15 atm. Rabbits were observed for intraoperative complications and postoperative morbidity. All rabbit airways were sized to a 4-0 endotracheal tube (5.4-mm outer diameter). Balloon dilation was performed safely with no intraoperative complications in 25 of 30 cases. One rabbit developed transient cyanosis during balloon inflation. Three rabbits died while undergoing dilation with 10-mm balloons, and another rabbit developed respiratory failure shortly after the procedure. All rabbits that died perioperatively lacked endoscopic evidence of airway obstruction or gross trauma. Four rabbits developed postoperative feeding difficulties that did not correlate with balloon diameter or inflation pressure. Endoscopic balloon dilation is generally well tolerated in New Zealand white rabbits. Intraoperative mortality from cardiopulmonary arrest reaches 50% when the balloon diameter exceeds the airway diameter by 4.6 mm. Postoperative feeding difficulties may occur with any balloon diameter or inflation pressure. Additional animal studies are necessary to determine the short- and long-term histologic effects of balloon dilation on the airway.

  4. A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

    Institute of Scientific and Technical Information of China (English)

    QIAN WEN; LIMA; YAN-PING CHEN; LIN YANG; WEI LUO; XIAO-NING WANG

    2008-01-01

    Objective To establish an experimental model of early stage avascular necrosis of the femoral head (ANFH) caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methods ANFH was induced by a combination of hypersensitivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid. The pathological changes were detected with digital radiography (DR), computed tomography (CT), magnetic resonance imaging (MRI), ink artery infusion angiography, hematoxylin--eosin staining, and mmunohistochemistry. Results The imageological and athological changes corresponded to the clinical characteristics of early stage ANFH. DR showed bilaterally increased bone density, an unclear epiphyseal line, and blurred texture of cancellous bone. CT showed spot-like low-density imaging of cancellous bone, thinner cortical bone, osteoporosis, and an unclear epiphyseal line. MRI showed bone marrow edema and spot-like high signals in T2-weighted imaging in cancellous bone. Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head. HE staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat cell hypertrophy. Lmmunohistochemistry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit model of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective methods to treat early stage ANFH.

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

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    Yan Wo

    2014-12-01

    Full Text Available 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.

  6. LOW-DOSE RADIOACTIVE ENDOVASCULAR STENTS PREVENT NEOINTIMAL HYPERPLASIA IN RABBITS RESTENOSIS MODEL

    Institute of Scientific and Technical Information of China (English)

    任晓庆; 黄定九; 黄刚; 毛家亮

    2002-01-01

    Objective To evaluate the effects of low-dose radioactive stents on the prevention of restenosis in rabbit model. Methods The stents were bombarded with suitable charged particles of adapted energy in the cyclotron to create a proper mixture of the radionuclides 59Fe, 60Co, 58Co, 51Cr, and 54Mn. The radioactive stents were implanted in the iliac arteries of rabbits. The effects of radioactive stents on prevention of restenosis were assessed by angiography, histomorphometry and immunocytochemistry. Results All the iliac arteries that had been implanted with radioactive stents were patent on angiography and had no radiation complication during the 1~2 months of follow-up. There was a significant reduction in neointimal area (0.37±0.14mm2 vs. 0.81±0.10mm2, P<0.01), percent area stenosis (6.7±2.9% vs. 13.2±1.4%, P<0.01) and PCNA immunoreactive rate (2.00±1.58% vs. 10.88±6.98%, P<0.05) in the radioactive stent group compared with the control stent group. Conclusion Radioactive stents with an active of 0.91~1.65 μCi could inhibit SMC proliferation and neointimal hyperplasia in animal restenosis model. The low-dose radioactive stents are safe and feasible for prevention of restenosis.

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

    Science.gov (United States)

    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

  8. Acellular bi-layer silk fibroin scaffolds support tissue regeneration in a rabbit model of onlay urethroplasty.

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    Yeun Goo Chung

    Full Text Available Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a rabbit model of urethra repair. A bi-layer silk fibroin matrix was fabricated by a solvent-casting/salt leaching process in combination with silk fibroin film casting to generate porous foams buttressed by homogeneous silk fibroin films. Ventral onlay urethroplasty was performed with silk fibroin grafts (Group 1, N = 4 (Width × Length, 1 × 2 cm(2 in adult male rabbits for 3 m of implantation. Parallel control groups consisted of animals receiving small intestinal submucosa (SIS implants (Group 2, N = 4 or urethrotomy alone (Group 3, N = 3. Animals in all groups exhibited 100% survival prior to scheduled euthanasia and achieved voluntary voiding following 7 d of initial catheterization. Retrograde urethrography of each implant group at 3 m post-op revealed wide urethral calibers and preservation of organ continuity similar to pre-operative and urethrotomy controls with no evidence of contrast extravasation, strictures, fistulas, or stone formation. Histological (hematoxylin and eosin and Masson's trichrome, immunohistochemical, and histomorphometric analyses demonstrated that both silk fibroin and SIS scaffolds promoted similar extents of smooth muscle and epithelial tissue regeneration throughout the original defect sites with prominent contractile protein (α-smooth muscle actin and SM22α and cytokeratin expression, respectively. De novo innervation and vascularization were also evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Following 3 m post-op, minimal acute inflammatory reactions were elicited by silk fibroin scaffolds characterized by the presence of eosinophil granulocytes while SIS matrices promoted chronic inflammatory responses indicated by mobilization of mononuclear cell infiltrates. The results

  9. Enhanced healing of rabbit segmental radius defects with surface-coated calcium phosphate cement/bone morphogenetic protein-2 scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi; Hou, Juan; Yin, ManLi [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Wang, Jing, E-mail: biomatwj@163.com [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Liu, ChangSheng, E-mail: csliu@sh163.net [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China)

    2014-11-01

    Large osseous defects remain a difficult clinical problem in orthopedic surgery owing to the limited effective therapeutic options, and bone morphogenetic protein-2 (BMP-2) is useful for its potent osteoinductive properties in bone regeneration. Here we build a strategy to achieve prolonged duration time and help inducting new bone formation by using water-soluble polymers as a protective film. In this study, calcium phosphate cement (CPC) scaffolds were prepared as the matrix and combined with sodium carboxymethyl cellulose (CMC-Na), hydroxypropylmethyl cellulose (HPMC), and polyvinyl alcohol (PVA) respectively to protect from the digestion of rhBMP-2. After being implanted in the mouse thigh muscles, the surface-modified composite scaffolds evidently induced ectopic bone formation. In addition, we further evaluated the in vivo effects of surface-modified scaffolds in a rabbit radius critical defect by radiography, three dimensional micro-computed tomographic (μCT) imaging, synchrotron radiation-based micro-computed tomographic (SRμCT) imaging, histological analysis, and biomechanical measurement. The HPMC-modified CPC scaffold was regarded as the best combination for segmental bone regeneration in rabbit radius. - Highlights: • A simple surface-coating method was used to fabricate composite scaffolds. • Growth factor was protected from rapid depletion via superficial coating. • Significant promotion of bone regeneration was achieved. • HPMC-modification displayed optimal effect of bone regeneration.

  10. Healing effects and superoxide dismutase activity of diode/Ga-As lasers in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Lee, Jae Yeon; Lee, Sang Ui; Lim, Taekjoo; Choi, Seok Hwa

    2014-01-01

    Osteoarthritis is a major cause of pain and disability in joints. The present study investigated the effects of differences of wavelengths and continuous versus pulsed delivery modes of low-level laser therapy (LLT) in a rabbit model of osteoarthritis. Comparison of the healing effects and superoxide dismutase (SOD) activity between therapy using diode and Ga-As lasers was our primary interest. Simple continuous wave (808-nm diode) and super-pulsed wave (904-nm Ga-As) lasers were used. Osteoarthritis was induced by injecting hydrogen peroxide into the articular spaces of the right stifle in rabbits. The rabbits were randomly assigned to four groups: normal control without osteoarthritis induction (G1), osteoarthritis-induction group without treatment (G2), osteoarthritis induction with diode irradiation (G3), and osteoarthritis induction with Ga-As irradiation (G4). Laser irradiation was applied transcutaneously for 5 min every day for over four weeks, starting the first day after confirmation of induction of osteoarthritis. The induction of osteoarthritis and effects of LLT were evaluated by biochemistry, computed tomography, and histological analyses. The SOD activity in G3 and G4 rabbits at two and four weeks after laser irradiation was significantly higher than that of G1 animals (plasers are similarly effective in healing and inducing SOD activity for LLT applications in a rabbit model of OA. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Effect of local viral transfer of interleukin 10 gene on a rabbit arthritis model induced by interleukin 1β

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ning; CUI Hua-dong; XUE Hong-xia

    2008-01-01

    Backgroud Interleukin 1β(IL-1 β)is the principal mediator in the pathogenesis of rheumatoid arthdtis.Continuous injection of interleukin 1β(IL-1β)into the knee articular cavities of anamals can induce models that resemble rheumatoid arthritis.The obiective of this study was to evaluate the feasibility of local recombinant retrovirus viral intedeukin 10(rRV-vIL-10)gene transfer treatment of a rabbit model of arthritis induced by IL-1β.Methods An hIL-1β-induced rabbit rheumatoid arthdtis model was established using the MFG-hIL-1β-neo-HIG-82 cell line,which is capable of continuous secretion of hIL-1a.After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1β-neo-HIG-82)with rRV-vIL-10,G418 was then added to identify the positive clone.The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection.Successful gene transfer was determined by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.The levels of IL-1β before and after treatment were determined by enzyme-linked immunosorbent assay.Results Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry.The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1β.Conclusions Retrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit syrnovium ex vivo and was able to suppress intra-articular inflammation response to IL-1β.

  12. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model

    Directory of Open Access Journals (Sweden)

    Christoforidis J

    2012-01-01

    Full Text Available John Christoforidis1, Robert Ricketts1, Cedric Pratt1, Jordan Pierce1, Scott Bean1, Michael Wells1, Xiaoli Zhang2, Krista La Perle31College of Medicine, 2Center for Biostatistics, 3College of Veterinary Medicine, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal pegaptanib, bevacizumab, and ranibizumab on blood-vessel formation during cutaneous wound healing in a rabbit model and to compare this effect to placebo controls.Methods: Forty New Zealand albino rabbits underwent full thickness cutaneous wounds using 6-mm dermatologic punch biopsies. The rabbits were assigned to four groups of ten, each receiving intravitreal injections of pegaptanib, bevacizumab, ranibizumab, or no injection (untreated controls. Five rabbits from each group underwent wound harvesting on day 7 and five from each group on day 14. The skin samples were stained with hematoxylin and eosin (HE, Masson's trichrome (MT, and CD34 for vascular endothelial cells. Semiquantitative evaluation of HE- and MT-stained slides was performed by one pathologist. Quantitative assessment of mean neovascularization (MNV scores was obtained from five contiguous biopsy margin 400× fields of CD34-stained sections by four independent observers.Results: Week 1 MNV scores in CD-34 stained sections were: untreated controls: 11.51 ± 4.36; bevacizumab: 7.41 ± 2.82 (P = 0.013; ranibizumab: 8.71 ± 4.08 (P = 0.071; and pegaptanib: 10.15 ± 5.59 (P = 0.378. Week 2 MNV data were: untreated controls: 6.14 ± 2.25; bevacizumab: 7.25 ± 2.75 (P = 0.471; ranibizumab: 4.53 ± 3.12 (P = 0.297; and, pegaptanib: 6.35 ± 3.09 (P = 0.892. Interobserver variability using intraclass correlation coefficient was 0.961.Conclusions: At week 1, all three anti-VEGF agents had suppressed MNV scores compared to controls. Although not statistically significant, there was an inhibitory trend, particularly with bevacizumab and ranibizumab. These effects were diminished at 2 weeks

  13. Percutaneous ultrasonic debridement of tendinopathy-a pilot Achilles rabbit model.

    Science.gov (United States)

    Kamineni, Srinath; Butterfield, Timothy; Sinai, Anthony

    2015-05-20

    Tendinopathy is a common clinical pathology, with mixed treatment results, especially when chronic. In this study, we examine the effects of an ultrasonic debridement modality in a rabbit tendinopathy model. We asked four questions: (1) Was it possible to create and visualize with ultrasound a tendinopathy lesion in a rabbit Achilles tendon? (2) Was it possible to guide a 19-gauge ultrasonic probe into the tendinopathy lesion? (3) Following ultrasonic treatment, was tendinopathy debris histologically present? and (4) Was the collagen profile qualitatively and quantitatively normalized following treatment? Skeletally mature female New Zealand white rabbits (n = 12) were injected with, ultrasonography localization, 0.150 ml of collagenase into the Achilles tendon. The collagenase-induced Achilles tendinopathy (3 weeks) was treated with percutaneous ultrasonic debridement. The tendons were harvested, at 3 weeks after treatment, and were subjected to histological assessment (modified Movin score) and biochemical analysis (collagen isoform content). Histopathological examination revealed that all tendons injected with collagenase showed areas of hypercellularity and focal areas of tendon disorganization and degeneration. The treated tendons had lower (improved) histopathological scores than injured tendons (P tendon, to qualitative and semi-quantitative levels of a normal tendon. We were successfully able to create a collagenase-injected tendinopathy lesion in a rabbit Achilles tendon and visualize the lesion with an ultrasound probe. A 19-gauge ultrasonic probe was inserted into the tendinopathic lesion under direct ultrasound guidance, and minimal tendinopathic debris remained after treatment. The treated tendon demonstrated a normalized qualitative and semi-quantitative collagen profile and improved histological appearance in the short term. This technique demonstrates scientific merit with respect to the minimally invasive treatment of tendinopathy and warrants

  14. Utilizing rabbit immunoglobulin G (IgG) protein for mark-capture studies on the desert subterranean termite, Heterotermes aureus (Snyder)

    Science.gov (United States)

    A series of mark-capture dispersal studies were conducted to investigate the feasibility of marking the southwestern desert subterranean termite, Heterotermes aureus (Snyder) with rabbit immunoglobulin G (IgG) protein. In turn, short-range dispersal patterns of H. aureus were measured across a 20-m ...

  15. [The purification and isolation of a new type of rabbit-origin lipopolysaccharide binding protein and the study of its biological function in vitro].

    Science.gov (United States)

    Ge, Xiao-Dong; Liu, You-Sheng; Wang, Xiao-Dong; Pan, Feng; Zhou, Ping

    2003-02-01

    To isolate and purify a new type of lipopolysaccharide binding protein (LBP) from burn rabbit serum, and to investigate its biological functions. Rabbits subjected to burn injury and endotoxemia were employed. The serum from the rabbits was purified by two-steps of ion-exchange chromatography (Bio-Rex 70 Resin, Mono-Q) and gel chromatography. Furthermore, the serum was identified by flow cytometry analysis, agglomeration test with sheep erythrocyte, and amino end amino acid residue sequencing. The obtained protein was applied to cultured human monocytes (U937), and the cytokine secretion such as TNFalpha from the U937 was observed. The molecular weight of the harvested protein was 48 kDa, and the 10 amino acid sequence at N end was arranged as GSQGTFTSEE, which was different to the amino acid sequence in NCBI protein bank and was so named P48. P48 possessed similar function to that of LBP and could promote the binding of LPS in a very low concentration with peripheral blood monocytes (PBMC), and also promote the TNFalpha secretion from U937. P48, a new type of LBP, could be isolated and purified from the burn rabbit serum. P48 possessed similar biological activities to that of LBP and could promote the process of inflammatory reaction.

  16. Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma

    NARCIS (Netherlands)

    Brus, F; vanOeveren, W; Heikamp, A; Okken, A; Oetomo, SB

    We investigated whether leakage of protein in lungs of pre term ventilated rabbits of 28- and 29-d gestational age is correlated with activation of clotting, complement, and polymorphonuclear leukocytes (PMN) in plasma. We found signs of systemic activation of clotting, complement, and PMN in

  17. Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma

    NARCIS (Netherlands)

    Brus, F; vanOeveren, W; Heikamp, A; Okken, A; Oetomo, SB

    1996-01-01

    We investigated whether leakage of protein in lungs of pre term ventilated rabbits of 28- and 29-d gestational age is correlated with activation of clotting, complement, and polymorphonuclear leukocytes (PMN) in plasma. We found signs of systemic activation of clotting, complement, and PMN in ventil

  18. A 17.6 kbp region located upstream of the rabbit WAP gene directs high level expression of a functional human protein variant in transgenic mouse milk

    NARCIS (Netherlands)

    Bischoff, Rainer; Degryse, E.; Perraud, F.; Dalemans, W.; Ali-Hadji, D.; Thepot, D.; Devinoy, E.; Houdebine, L.M.; Pavirani, A.

    1992-01-01

    We have investigated whether DNA regions present in the rabbit whey acidic protein (WAP) promoter/5' flanking sequence could potentially confer, in vivo, high level expression of reporter genes. Transgenic mice were generated expressing a variant of human alpha 1-antitrypsin, which has inhibitory ac

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    Fei Yuan

    2014-01-01

    Full Text Available 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.

  1. Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model.

    Science.gov (United States)

    Drobyshevsky, Alexander; Cotten, C Michael; Shi, Zhongjie; Luo, Kehuan; Jiang, Rugang; Derrick, Matthew; Tracy, Elizabeth T; Gentry, Tracy; Goldberg, Ronald N; Kurtzberg, Joanne; Tan, Sidhartha

    2015-01-01

    Cerebral palsy (CP) has a significant impact on both patients and society, but therapy is limited. Human umbilical cord blood cells (HUCBC), containing various stem and progenitor cells, have been used to treat various brain genetic conditions. In small animal experiments, HUCBC have improved outcomes after hypoxic-ischemic (HI) injury. Clinical trials using HUCBC are underway, testing feasibility, safety and efficacy for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model of CP after acute changes secondary to HI injury had subsided. Following uterine ischemia at 70% gestation, we infused HUCBC into newborn rabbit kits with either mild or severe neurobehavioral changes. Infusion of high-dose HUCBC (5 × 10(6) cells) dramatically altered the natural history of the injury, alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test, however, showed that joint function did not restore to naïve control function in either group. Tracing HUCBC with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. This is the first study to show that HUCBC improve motor performance in a dose-dependent manner, perhaps by improving compensatory repair processes. © 2015 S. Karger AG, Basel.

  2. Validation of a genu valgum model in a rabbit hind limb.

    Science.gov (United States)

    Mast, Nicholas; Brown, Nicholas A T; Brown, Cassandra; Stevens, Peter M

    2008-01-01

    Numerous techniques exist to correct pediatric angular deformity by asymmetrically inhibiting physeal growth. Despite decades of surgical experience, little is known about the determinants of success or failure of temporary hemiepiphysiodesis. We lack a basic understanding of tolerances and kinematics of the surgically restrained physis. Furthermore, little is known about the influence of implant design and placement on efficacy of deformity correction and rebound growth. We have undertaken a pilot research study with the goal of producing genu valgum in New Zealand white rabbits. This report comprises our initial experience and observations in performing hemiepiphysiodesis with staples and 2-hole plate techniques. The experimental hypotheses proposed by this article are as follows: (1) a staple or plate applied to the proximal lateral tibial physis of a rabbit hind limb will reliably create a valgus deformity of the knee; (2) the plate or staple will create this deformity without permanently damaging the proximal tibial physis; and (3) provided the implant remains in situ, there will be no difference between the plate and staple constructs with respect to the magnitude or rate of deformity produced. Further studies will aim to use this model to investigate technical issues related to physeal instrumentation.

  3. Experimental intra-arterial administration of SR-2508 in the rabbit V2 carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Coldwell, D.M.; Huff, J.; Marcellus, H.; Coldwell, S.G.

    1989-03-01

    The use of the nitroimidazole radiation sensitizers, misonidazole and SR-2508, has been limited by a variety of side-effects, principally peripheral neuropathies. To increase the effectiveness of radiosensitization and reduce the administered dose of the sensitizers, intra-arterial delivery of SR-2508 was performed and followed with 10Gy of 4 MeV photon beam radiotherapy in the rabbit V2 carcinoma tumour model. Comparison was made with rabbits treated with an identical dose of SR-2508 given intravenously prior to photon beam radiotherapy. Control animals were treated with radiation therapy only, intra-arterial SR-2508 only, or had no treatment. Neither radiation therapy alone nor SR-2508 alone had any effect on tumour growth. In the intra-arterial group, tumour growth was slower and size was significantly smaller than all other groups. Results suggest that the intra-arterial infusion of radiation sensitizer produces greater tumour response than intravenous infusion when each is combined with radiation therapy.

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

    Science.gov (United States)

    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.

  5. Cellular Imaging Using Equivalent Cross-Relaxation Rate Technique in Rabbit VX-2 Tumor Model.

    Science.gov (United States)

    Nishiofuku, Hideyuki; Matsushima, Shigeru; Taguchi, Osamu; Inaba, Yoshitaka; Yamaura, Hidekazu; Sato, Yozo; Tanaka, Toshihiro; Kichikawa, Kimihiko

    2011-01-01

    Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement technique that can be used to quantitatively evaluate changes in structural organization and cellular density by MRI. The aim of this study was to evaluate the correlation between the ECR value and cellular density in the rabbit VX2 tumor model. Five rabbits implanted with 10 VX2 tumors in the femur muscles were included in this study. We adopted the off-resonance technique with a single saturation transfer pulse frequency of 7 ppm downfield from water resonance. The ECR value was defined as the percentage of signal loss between the unsaturated and saturated images. ECR images were constructed based on the percentage of the ECR value. Pathological specimens were divided into 34 areas and classified into two groups: the viable group and the necrotic group. ECR values were measured and compared between groups. The correlation between the ECR value and cellular density was then determined. The mean ECR value was significantly higher in the viable group than in the necrotic group (61.2% vs. 35.8%). The area under the curve that calculated by receiver operating characteristic curve was 0.991 at 7 ppm. The regression graph showed a linear relationship between the ECR value and cellular density; the correlation coefficient (r) was 0.858. There is a strong association between the ECR value and cellular density in VX2 tumors and so ECRI could be a potentially useful technique for accurately depicting viable and necrotic areas.

  6. Protective effects of prostaglandin E1 perfusion against spinal cord ischemia-reperfusion injury in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Xifan Mei; Yansong Wang; Chang Liu

    2008-01-01

    BACKGROUND: Prostaglandin E1 (PGE1) is known to be protective in ischemia-reperfusion of heart, lung, renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE: To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING: Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS: Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used: prostaglandin El injectable powder, as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS: We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 (100 ng/kg/min). MAIN OUTCOME MEASURES: The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS: All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group (P<0

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

    Directory of Open Access Journals (Sweden)

    Marc-Antoine Isorni

    2015-01-01

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

  8. [Modeling neuropathologic syndromes by creating generators of pathologically enhanced excitation in the hypothalamus of rabbits].

    Science.gov (United States)

    Kryzhanovskiĭ, G N; Kotov, A V; Kulygina, O A; Tolpygo, S M; Sudakov, K V

    1977-10-01

    In the experiments on free behavior rabbits, tetanus toxin was injected into "pacemaker" motivational emotiogenic regions of the hypothalamus to form generators of pathologically enhanced excitation; this produced stable, long-term disorders in motivational-emotional behavior. The changes were manifested by intensification of the feeding behavior activity, including increase of the "secondary motivational reactions", intensification of the motor activity, excessive number of automatic masticatory movements, appearance of aggression, fear reaction and corresponding vegetative changes. The character of these reactions depended on the site of the toxin administration and on its dose. Formation of long-term generators of the pathologically enhanced excitation in the "pacemaker" motivational-emotiogenic centers of the hypothalamus by tetanus toxin can be used the modelling of psychopathological states in animals. The data obtained on the new model have confirmed the theory of generative mechanisms of neuropathological syndromes characterized by hyperactivity of the systems.

  9. Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model

    Directory of Open Access Journals (Sweden)

    Sun HL

    2013-10-01

    Full Text Available Hongliang Sun,1 Linfeng Xu,1 Tianyuan Fan,2 Hongzhi Zhan,3 Xiaodong Wang,3 Yanfei Zhou,2 Ren-jie Yang3 1Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 2Pharmacy School of Beijing University, Beijing, 3Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles. Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done. Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413. Seven to 26

  10. Modelling of proteins in membranes

    DEFF Research Database (Denmark)

    Sperotto, Maria Maddalena; May, S.; Baumgaertner, A.

    2006-01-01

    This review describes some recent theories and simulations of mesoscopic and microscopic models of lipid membranes with embedded or attached proteins. We summarize results supporting our understanding of phenomena for which the activities of proteins in membranes are expected to be significantly...... affected by the lipid environment. Theoretical predictions are pointed out, and compared to experimental findings, if available. Among others, the following phenomena are discussed: interactions of interfacially adsorbed peptides, pore-forming amphipathic peptides, adsorption of charged proteins onto...... oppositely charged lipid membranes, lipid-induced tilting of proteins embedded in lipid bilayers, protein-induced bilayer deformations, protein insertion and assembly, and lipid-controlled functioning of membrane proteins....

  11. Disposable rabbit

    Science.gov (United States)

    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.

  12. Disposal rabbit

    Science.gov (United States)

    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.

  13. Improved Bone Formation in Osteoporotic Rabbits with the Bone Morphogenetic Protein-2 (rhBMP-2 Coated Titanium Screws Which Were Coated By Using Plasma Polymerization Technique

    Directory of Open Access Journals (Sweden)

    Salih Gulsen

    2014-06-01

    Full Text Available Delaying of bone fusion in osteoporotic patients underwent spinal stabilization surgery leads to screw loosening, and this causes pseudoarticulation, mobility and fibrosis at vertebral segments. To prevent these complications, the screws coated with recombinant bone morphogenetic protein-2 (rhBMP-2 could be used. To verify this hypothesis, we coated 5 Titanium screws with rhBMP-2 using plasma polymerization method, and also used 10 uncoated screws for making comparison between coated and uncoated screws in different groups. And 15 skeletally mature white New Zealand female rabbits were assigned into three different groups: Group 1(N = 5: No osteoporosis induction and insertion of uncoated Titanium screw into right sacrum of each rabbit in group 1; group 2 (N = 5: Osteoporosis induction and insertion of uncoated Titanium screw into right sacrum of each rabbit in group 2; group 3 (N = 5 rhBMP-2 coated Titanium screw inserted into right sacrum of each rabbit in group 3. In summary, using of these coated screws provides new bone formation, but causes less fibrosis and less inflammation than uncoated screws at the interface between the coated screw and bone. Then the plasma polymerization technique provides controlled releasing of rhBMP-2 from the screw to the bone tissue in osteoporotic rabbits.

  14. Tissue-specific expression, hormonal regulation and 5'-flanking gene region of the rat Clara cell 10 kDa protein: comparison to rabbit uteroglobin.

    Science.gov (United States)

    Hagen, G; Wolf, M; Katyal, S L; Singh, G; Beato, M; Suske, G

    1990-01-01

    The amino acid sequence of rat Clara Cell 10 kDa secretory protein (CC10) shows 55% identity to rabbit uteroglobin. In order to define the relationship between rat CC10 and rabbit uteroglobin in detail, the tissue-specific expression and hormonal regulation of rat CC10 mRNA was analyzed. We report that like rabbit uteroglobin, rat CC10 mRNA is expressed in lung and esophagus, as well as in uteri of estrogen- and progesterone-treated females. Expression of CC10 mRNA in lung is regulated by glucocorticoids. The similarity in expression pattern of rat CC10 mRNA and rabbit uteroglobin mRNA is reflected by a striking similarity in the 5'-flanking regions of the two genes. Despite this overall similarity, two regions of 0.3 kb and 2.1 kb are absent in the rat CC10 upstream gene region. The larger region includes a cluster of hormone receptor binding sites, believed to be responsible for differential regulation of rabbit uteroglobin by glucocorticoids and progesterone. Thus, while the sequence identities in the coding and 5'-flanking regions point towards a common ancestor for the uteroglobin and CC10 gene, later events (deletions/insertions) might have caused species-specific differences in their regulation. Images PMID:2349092

  15. Yeast expressed recombinant Hemagglutinin protein of Novel H1N1 elicits neutralising antibodies in rabbits and mice

    Directory of Open Access Journals (Sweden)

    Athmaram TN

    2011-11-01

    Full Text Available Abstract Currently available vaccines for the pandemic Influenza A (H1N1 2009 produced in chicken eggs have serious impediments viz limited availability, risk of allergic reactions and the possible selection of sub-populations differing from the naturally occurring virus, whereas the cell culture derived vaccines are time consuming and may not meet the demands of rapid global vaccination required to combat the present/future pandemic. Hemagglutinin (HA based subunit vaccine for H1N1 requires the HA protein in glycosylated form, which is impossible with the commonly used bacterial expression platform. Additionally, bacterial derived protein requires extensive purification and refolding steps for vaccine applications. For these reasons an alternative heterologous system for rapid, easy and economical production of Hemagglutinin protein in its glycosylated form is required. The HA gene of novel H1N1 A/California/04/2009 was engineered for expression in Pichia pastoris as a soluble secreted protein. The full length HA- synthetic gene having α-secretory tag was integrated into P. pastoris genome through homologous recombination. The resultant Pichia clones having multiple copy integrants of the transgene expressed full length HA protein in the culture supernatant. The Recombinant yeast derived H1N1 HA protein elicited neutralising antibodies both in mice and rabbits. The sera from immunised animals also exhibited Hemagglutination Inhibition (HI activity. Considering the safety, reliability and also economic potential of Pichia expression platform, our preliminary data indicates the feasibility of using this system as an alternative for large-scale production of recombinant influenza HA protein in the face of influenza pandemic threat.

  16. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds

    NARCIS (Netherlands)

    Holland, T.A.; Bodde, E.W.H.; Baggett, L.S.; Tabata, Y.; Mikos, A.G.; Jansen, J.A.

    2005-01-01

    In this study, hydrogel scaffolds, based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF), were implanted into osteochondral defects in the rabbit model. Scaffolds consisted of two layers-a bottom, bone forming layer and a top, cartilage forming layer. Three scaffold formulations were impl

  17. The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model

    DEFF Research Database (Denmark)

    Henriksen, Maiken Lumby; Teisner, Ane; Kjeldsen, Jens

    2016-01-01

    and Methods: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNF) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration...

  18. Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model.

    NARCIS (Netherlands)

    Guo, X.; Park, H.; Young, S.; Kretlow, J.D.; Beucken, J.J.J.P. van den; Baggett, L.S.; Tabata, Y.; Kasper, F.K.; Mikos, A.G.; Jansen, J.A.

    2010-01-01

    This work investigated the delivery of marrow mesenchymal stem cells (MSCs), with or without the growth factor transforming growth factor-beta1 (TGF-beta1), from biodegradable hydrogel composites on the repair of osteochondral defects in a rabbit model. Three formulations of oligo(poly(ethylene glyc

  19. Modelo experimental de osteotomia em coelhos imaturos Expeimental model for osteotomy in immature rabbit

    Directory of Open Access Journals (Sweden)

    Marcos Almeida Matos

    2001-12-01

    Full Text Available Apresenta-se um modelo experimental de osteotomia de fíbula em coelhos com esqueleto imaturo adequado para o estudo do processo de reparação óssea. A osteotomia foi realizada por serra elétrica padronizada, sem utilização de dispositivos de fixação. Este modelo foi testado em cinco coelhos e constou da descrição detalhada de técnica operatória, anestesia e técnica radiográfica. Os animais foram submetidos a eutanásia após cinco semanas e tiveram suas fíbulas encaminhadas para avaliação histológica. Comprovou-se que o modelo é eficiente, simples e de fácil execução, tornando-se opção atraente para todos aqueles que desejam realizar estudos de consolidação óssea durante a imaturidade esquelética.Authors present an experimental model for fibular osteotomy in immature rabbits usefull to study healing bone process. Osteotomy was produced by means of eletric saw without utilization of fixing devices. This model was applied in five rabbit were sacrified after five weeks and had their fibular send for histological evaluation. Operative technique, anesthesia, roetigenografic technique were detailed discribed. The model was proved to be efficient, simple and of easy execution, becoming an atractive option for whoever wish to perform studies of bone healing through skeleon development.

  20. A radioactive seed implant on a rabbit's liver following a voxel model representation for dosimetric proposals

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Tarcisio P.R.; Andrade, Joao Paulo Lopes de; Costa, Igor Temponi; Teixeira, Cleuza H. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Programa de Pos-graduacao em Ciencias e Tecnicas Nucleares]. E-mail: campos@nuclear.ufmg

    2005-07-01

    Animal models have been used in experimentation with ionizing radiation. The evaluation of the energy absorbed per unit tissue mass in vivo transported by nuclear particles is a task to be performed before experimentation. Stochastic or deterministic methodology can be applied, however the dosimetric protocols applied in radiotherapy center cannot be applied directly due to the inherent small geometry and chemical composition of the animal distinct from human. The present article addresses a method in development that will predict the dose distribution into the rabbit thorax based on the solution of the transport phenomena in a voxel model. The model will be applied to simulate a seed implant experiment on a rabbit. Herein, the construction of the three-dimensional voxel model anthropomorphic -anthropometrics to the rabbit is presented. The model is assembling from a set of computer tomography of the rabbit. The computational phantom of the thorax starts at the digitalisation of the CT images, tissue definition, and color image representation of each tissue and organ. The chemical composition and mass density of each tissue is evaluated as similar date presented by ICRU-44. To treat the images, a code namely SISCODES, developed in house, was used. The in vivo experiment that will be simulated is also described. That is a implant of five seeds of 1.6x2 mm performed in a rabbit's liver. The perspective of this work is the application of the model in dosimetric studies predicting the dose distribution around the seed's implanted in vivo experiments. (author)

  1. Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein.

    NARCIS (Netherlands)

    Shahrooei, M.; Hira, V.; Stijlemans, B.; Merckx, R.; Hermans, P.W.M.; Eldere, J. van

    2009-01-01

    Several well-studied proteins with defined roles in Staphylococcus epidermidis biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (S. epidermidis surface protein C; accession no. NP_765787) as a target for antibodie

  2. Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein.

    NARCIS (Netherlands)

    Shahrooei, M.; Hira, V.; Stijlemans, B.; Merckx, R.; Hermans, P.W.M.; Eldere, J. van

    2009-01-01

    Several well-studied proteins with defined roles in Staphylococcus epidermidis biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (S. epidermidis surface protein C; accession no. NP_765787) as a target for

  3. Do Different Cyclooxygenase Inhibitors Impair Rotator Cuff Healing in a Rabbit Model?

    Institute of Scientific and Technical Information of China (English)

    Yi Lu; Yue Li; Feng-Long Li; Xu Li; Hong-Wu Zhuo; Chun-Yan Jiang

    2015-01-01

    Background:The effect of selective and non-selective cyclooxygenase (COX) inhibitors on tendon healing was variable.The purpose of the study was to evaluate the influence of non-selective COX inhibitor,ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor,celecoxib on the tendon healing process in a rabbit model.Methods:Ninety-six New Zealand rabbits were used as rotator cuff repair models.After surgery,they were divided randomly into four groups:Ibuprofen (10 mg·kg-1·d-1),celecoxib (8 mg·kg 1·d 1),flurbiprofen axetil (2 mg·kg 1·d-1),and control group (blank group).All drugs were provided for 7 days.Rabbits in each group were sacrificed at 3,6,and 12 weeks after tendon repair.Tendon biomechanical load failure tests were performed.The percentage of type Ⅰ collagen on the bone tendon insertion was calculated by Picric acid Sirius red staining and image analysis.All data were compared among the four groups at the same time point.All data in each group were also compared across the different time points.Qualitative histological evaluation of the bone tendon insertion was also performed among groups.Results:The load to failure increased significantly with time in each group.There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks (0.533 vs.0.700,P =0.002),6 weeks (0.607 vs.0.763,P =0.01),and 12 weeks (0.660 vs.0.803,P =0.002),and significantly lower percentage of type Ⅰ collagen at 3 weeks (l 1.5% vs.27.6%,P =0.001),6 weeks (40.5% vs.66.3%,P =0.005),and 12 weeks (59.5% vs.86.3%,P =0.001).Flurbiprofen axetil showed significant differences at 3 weeks (failure load:0.600 vs.0.700,P =0.024;percentage of type Ⅰ collagen:15.6% vs.27.6%,P =0.001),but no significant differences at 6 and 12 weeks comparing with control group,whereas the ibuprofen groups did not show any significant difference at each time point.Conclusions:Nonsteroidal anti-inflammatory drugs can delay tendon healing in the

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

    Science.gov (United States)

    Zheng, Wenjing; Ma, Mingming; Du, Ergang; Zhang, Zhengwei; Jiang, Kelimu; Gu, Qing; Ke, Bilian

    2015-11-01

    The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate‑buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain‑optical coherence tomography. Tear membrane break‑up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription‑quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultrastructure7 days after treatment. The percentages of apoptotic corneal‑ and Cj‑ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10

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

    Science.gov (United States)

    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

    2015-07-14

    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.

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

    Directory of Open Access Journals (Sweden)

    Julio Jiménez

    2016-10-01

    Full Text Available 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.

  7. Quantitative analysis of disc degeneration using axial T2 mapping in a percutaneous annular puncture model in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Jee Won; Kim, Su Jin [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Heung Sik; Lee, Joon Woo [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Hong, Sung Hwan [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-02-15

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

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

    Directory of Open Access Journals (Sweden)

    Willy W. Suen

    2015-07-01

    Full Text Available 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.

  9. A rabbit model of pediatric nonalcoholic steatohepatitis:The role of adiponectin

    Institute of Scientific and Technical Information of China (English)

    Jun-Fen Fu; Yan-Lan Fang; Li Liang; Chun-Lin Wang; Fang Hong; Guan-Ping Dong

    2009-01-01

    AIM: To create a rabbit model of pediatric nonalcoholic steatohepatitis (NASH) and to evaluate the role of adiponectin in the process. METHODS: Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups: (1) the normal control group ( n = 10) was fed with standard diet for 12 wk; (2) the model group A ( n = 11); and (3) model group B ( n = 11) were fed with a highfat diet (standard diet + 10% lard + 2% cholesterol) for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α were measured. RESULTS: Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis.Compared with the normal control group, there were significant increases in model groups A and B in weight gain (1097.2 ± 72.3, 1360.5 ± 107.6 vs 928.0 ± 58.1, P < 0.05, P < 0.01), liver weight (93.81 ± 6.64, 104.6 ± 4.42 vs 54.4 ± 1.71, P < 0.01), Lg (ALT) (1.9 ± 0.29, 1.84 ± 0.28 vs 1.60 ± 0.17, P < 0.01), and Lg (TG) (1.03 ± 0.24, 1.16 ± 0.33 vs 0.00 ± 0.16, P < 0.01). Weight gain was much more in model group B than in model group A (1360.5 ± 107.6 vs 1097.2 ± 72.3, P < 0.05). But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines (IL-6 and TNF-α) increased in model group B compared with that of control and model group A (IL-6: 1.86 ± 0.21 vs 1.41 ± 0.33, 1.38 ± 0.42, P < 0.01; TNF-α: 1.18 ± 0.07 vs 0.66 ± 0.08, 0.86 ± 0.43, P < 0.01, P < 0.05),whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control (adiponectin:A: 21.87 ± 4.84 and B: 21.48 ± 4.60 vs 27.36 ± 7.29,P < 0.05. IL-10: A: 1.72 ± 0.38 and B: 1.83 ± 0.39 vs 2.26 ± 0.24, P < 0.01). Lg (TC) and

  10. Effect of nano-hydroxyapatite/collagen composite and bone morphogenetic protein-2 on lumbar intertransverse fusion in rabbits

    Institute of Scientific and Technical Information of China (English)

    孙天胜; 关凯; 时述山; 朱兵; 郑永军; 崔福斋; 张伟; 廖素三

    2004-01-01

    Objective: To investigate the effect of nano-hydroxyapatite/collagen (nHA/collagen) composite as a graft extender and enhancer when combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar intertransverse fusion in rabbits.Methods: Sixty-four adult female New Zealand white rabbits, aged 1 year and weighing 3.5-4.5 kg, underwent similar posterolateral intertransverse process arthrodesis and were randomly divided into 4 groups based on different grafts: autogenous cancellous bone alone (ACB group), nHA/collagen alone (HAC group), half autogenous cancellous bone and half nHA/collagen (ACB+HAC group) and nHA/collagen combined with rhBMP-2 (HAC+BMP group). The fusion masses were analyzed by manual palpation, radiography, biomechanical testing and histological examination. Results: Fusion was observed in 4 cases in the 6th week and in 5 cases in the 10th week after surgery in ACB group. No case showed fusion in HAC group. In ACB+HAC group, there was fusion in 3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC+BMP group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and in 6 cases in the 10th week after surgery. It suggested that ACB, ACB+HAC and HAC+BMP groups showed similar fusion ratio and mechanical strength in the 6th and 10th week after surgery. According to the microstructure analysis of the samples, nHA/collagen had no negative effect when implanted together with ilium autograft. In HAC+BMP group, new bone-like tissue was observed in the 2nd week postoperatively, and nearly all of the implanted composites were replaced by mature bone matrix and new bones in 10th week postoperatively.Conclusions: The nHA/collagen, especially combined with rhBMP-2, is a promising bone substitute, for it has quick biodegradation, fine bone-bending ability, and high osteoconductivity on posterolateral spinal fusion in rabbits.

  11. Paradoxical effects of KB-R7943 on arrhythmogenicity in a chronic myocardial infarction rabbit model.

    Science.gov (United States)

    Chang, Po-Cheng; Wo, Hung-Ta; Lee, Hui-Ling; Wen, Ming-Shien; Chou, Chung-Chuan

    2015-07-01

    Na(+)/Ca(2+) exchanger blockade has been reported to be anti-arrhythmic in different models. The effects of KB-R7943, a Na(+)/Ca(2+) exchanger blocker, on arrhythmogenesis in hearts with chronic myocardial infarction (MI) remain unclear. Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine rabbit hearts with chronic MI and four control hearts. Electrophysiology studies including inducibility of ventricular tachyarrhythmias, ventricular fibrillation dominant frequency, action potential, Cai alternans, Cai decay, and conduction velocity were performed. The same protocol was repeated in the presence of KB-R7943 (0.5, 1, and 5μM) after the baseline studies. KB-R7943 was effective in suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias in hearts with chronic MI. Surprisingly, KB-R7943 increased the inducibility of ventricular tachyarrhythmias in a dose-dependent manner (11%, 11%, 22%, and 56% at baseline and with 0.5, 1, and 5μM KB-R7943, respectively, p=0.02). Optical mapping analysis revealed that the underlying mechanisms of the induced ventricular tachyarrhythmias were probably spatially discordant alternans with wave breaks and rotors. Further analysis showed that KB-R7943 significantly enhanced both action potential (p=0.033) and Cai (p=0.001) alternans, prolonged Cai decay (tau value) in a dose-dependent manner (p=0.004), and caused heterogeneous conduction delay especially at peri-infarct zones during rapid burst pacing. In contrast, KB-R7943 had insignificant effects in control hearts. In this chronic MI rabbit model, KB-R7943 has contrasting effects on arrhythmogenesis, suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias, but enhancing the inducibility of tachyarrhythmias. The mechanism is probably the enhanced spatially discordant alternans because of prolonged Cai decay and heterogeneous conduction delay. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier

  12. Phosphorylation of acidic ribosomal proteins from rabbit reticulocytes by a ribosome-associated casein kinase

    DEFF Research Database (Denmark)

    Issinger, O G

    1977-01-01

    Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate polyacryl......Two acidic proteins from 80-S ribosomes were isolated and purified to homogeneity. The purified acidic proteins could be phosphorylated by casein kinase using [gamma-32P]ATP and [gamma-32P]GTP as a phosphoryl donor. The proteins became phosphorylated in situ, too. Sodium dodecyl sulfate...

  13. Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node

    OpenAIRE

    Xiang Li; Ji-qian Zhang; Jian-wei Shuai

    2014-01-01

    The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+ transient, and i Na changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of t...

  14. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    Yan-ping Song; Jian-ming Wang; Mei Zhang; Na Hui; Shi-ping Zhao; Kai Hu

    2009-01-01

    Objective To observe the expression of hypoxia inducible faetor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First, control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber, and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1, 3, 7 and 14 after retinal ischemla-reperfusion, respectively. Results No cells with HIF-la positive expression were observed in the retina of the control group. Ceils with HIF-1α positive expression in the model group outnumbered those in the control group (P < 0. 01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure, which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.

  15. Evaluation of a prednisolone acetate-loaded subconjunctival implant for the treatment of recurrent uveitis in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Marcus Ang

    Full Text Available AIM: To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model. METHODS: Randomized, controlled study of biodegradable microfilms preloaded with prednisolone acetate (PA in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC microfilms (n = 10 and blank microfilms (n = 6 were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period. RESULTS: In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded microfilms. The 60-40-60% microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P<0.001. The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded microfilms. CONCLUSION: Our pilot study demonstrated that a subconjunctival PA-loaded implant is effective in suppressing inflammation in the rabbit model of uveitis, by providing therapeutic levels of PA that attenuated the inflammatory response even after a rechallenge. Longer term studies are now needed to establish the therapeutic potential of such a delivery system for treatment of ocular inflammation.

  16. Can an Antibiotic (Macrolide) Prevent Chlamydia pneumoniae-Induced Atherosclerosis in a Rabbit Model?

    Science.gov (United States)

    Fong, Ignatius W.; Chiu, Brian; Viira, Esther; Jang, Dan; Fong, Michael W.; Peeling, Rosanna; Mahony, James B.

    1999-01-01

    There is increasing data implicating Chlamydia pneumoniae in the pathogenesis of atherosclerosis, and antibiotics may theoretically be useful to prevent secondary vascular complications. Three groups of New Zealand White specific-pathogen-free rabbits, fed cholesterol-free chow, were inoculated via the nasopharynx on three occasions, 2 weeks apart, with C. pneumoniae. Group I (n = 23) rabbits were untreated; group II (n = 24) rabbits were treated with azithromycin at 30 mg/kg of body weight daily for 3 days and then once every 6 days, starting 5 days after first inoculation and continuing until sacrifice (early treatment); and group III (n = 24) rabbits were treated with the same dose of azithromycin but initiated 2 weeks after the last inoculation. All animals were sacrificed at 10 to 11 weeks after initial inoculation and examined for signs of atherosclerosis of the aorta. Eight (34.8%) untreated rabbits developed early signs of atherosclerosis, whereas only one (4.2%) in the early-treatment group had such signs (P = 0.02). However, eight rabbits (33.3%) of the delayed-treatment group had atherosclerotic changes of the aorta and no significant reduction compared to untreated rabbits. Early treatment of C. pneumoniae-infected rabbits with azithromycin was highly effective (87%) in preventing atherosclerotic changes, but delayed treatment was ineffective. It is possible that longer or more aggressive antibiotic treatment may be needed to reverse preformed lesions or that antibiotics may not be of value once lesions have formed. PMID:10548582

  17. Relationship Between the Inoculum Dose of Streptococcus pneumoniae and Pneumonia Onset in a Rabbit Model

    Science.gov (United States)

    2005-04-01

    White rabbits (mean + or - SD + or - 4.75 + or - 0.25 kg (n = 27)). Rabbits were endobronchially inoculated with increasing doses of Streptococcus ... pneumoniae and pneumonia onset was observed over the following 96 h. The diagnostic approach was based on the Clinical Pulmonary Infection Score

  18. Development and characterization of a rabbit alveolar bone nonhealing defect model.

    NARCIS (Netherlands)

    Young, S.; Bashoura, A.G.; Borden, T.; Baggett, L.S.; Jansen, J.A.; Wong, M.; Mikos, A.G.

    2008-01-01

    The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 1

  19. A study of ribonucleoproteins: The sequence of rabbit 18S ribosomal RNA and the identification of proteins associated with messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Connaughton, J.F. Jr.

    1989-01-01

    This study considers the functional role of ribosomal RNA and messenger ribonucleoproteins in the translational regulation of gene expression. The primary structure of rabbit 18S ribosomal RNA was determined by nucleotide sequence analysis of the RNA directly. Rabbit 18S RNA was cleaved with either T{sub 1} ribonuclease or RNase H, using a Pst 1 DNA linker to generate a unique set of overlapping fragments spanning the entire molecule. Both intact and fragmented 18S RNA were end-labeled with {sup 32}P and base-specifically cleaved enzymatically and chemically. Nucleotide sequences were determined from long polyacrylamide sequencing gels run in formamide. To assess functional roles of RNA in gene expression, specific mRNA-protein interactions were also examined. Eukaryotic mRNA is associated with specific proteins that may be important in translational regulation and mRNA stability; mRNP complexes were reconstituted in a message-dependent, cell-free rabbit reticulocyte translation system, using unique mRNA species transcribed in vitro with SP6 polymerase. Transcripts of both rabbit and human {beta}-globin cDNA were labeled with {sup 32}P either throughout the molecule ore selectively at the 5{prime} and 3{prime} terminus.

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

    Science.gov (United States)

    Maeng, Jin Hee; Lee, Eunhye; Lee, Don Haeng; Yang, Su-Geun

    2013-06-01

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

  1. In vivo non-invasive serial monitoring of FDG-PET progression and regression in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Worthley, Stephen G; Zhang, Zhuang Y; Machac, Josef; Helft, Gérard; Tang, Cheuk; Liew, Gary Y H; Zaman, Azfar G; Worthley, Matthew I; Fayad, Zahi A; Buchsbaum, Monte S; Fuster, Valentin; Badimon, Juan J

    2009-03-01

    We investigated the ability of fluorodeoxyglucose positron emission tomography (FDG PET) imaging to serially monitor macrophage content in a rabbit model of atherosclerosis. Atherosclerosis was induced in rabbits (n = 8) by a combination of atherogenic diet and balloon denudation of the aorta. At the end of nine months, the rabbits were randomized to a further six months of the same atherogenic diet (progression group) or normal diet (regression group). In vivo uptake of FDG by the thoracic aorta was measured using aortic uptake-to-blood radioactivity ratios at the start and end of the randomized period. A significant increase in FDG uptake of the progression group after continued cholesterol feeding (aortic uptake-to-blood radioactivity: 0.57 +/- 0.02 to 0.68 +/- 0.02, P = 0.001), and a corresponding fall in FDG uptake of the regression group after returning to a normal chow diet (aortic uptake-to-blood radioactivity ratios: 0.67 +/- 0.02 to 0.53 +/- 0.02, P < 0.0001). FDG PET can quantify in vivo macrophage content and serially monitor changes in FDG activity in this rabbit model.

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

    Science.gov (United States)

    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.

  3. Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits.

    Science.gov (United States)

    Yan, Peng; Yang, Xiaohong; Yang, Xiaoyu; Zheng, Weidong; Tan, Yunbing

    2014-06-15

    Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9-10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation.

  4. Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2013-01-01

    Full Text Available We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105 cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

  5. Diverse effects of taurine on vascular response and inflammation in GSH depletion model in rabbits.

    Science.gov (United States)

    Ozsarlak-Sozer, G; Sevin, G; Ozgur, H H; Yetik-Anacak, G; Kerry, Z

    2016-04-01

    A reduction in GSH and an increase in free radicals are observed in inflammatory diseases, indicating oxidative stress. Taurine protects cells from the cytotoxic effects of inflammation. There have been limited studies to date evaluating the effect of taurine in oxidative stress-induced vascular dysfunction and its role in vascular inflammatory diseases. Therefore, we aimed to investigate the effect of taurine on the regulation of vascular tonus and vascular inflammatory markers in rabbit aortae and carotid arteries in oxidative stress-induced by GSH depletion. Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), GSH-depleting compound and/or taurine. Cumulative concentration-response curves for acetylcholine (ACh), phenylephrine and 5-hydroxytriptamine (5-HT) were constructed with or without Nω-nitro-L-arginine (LNA) in the carotid artery and aorta rings. Immunohistochemical staining was performed for TNF-α and IL-1β. BSO increased ACh-induced NO-dependent relaxations, phenylephrine-induced contractions in the carotid artery and 5-HT induced-contractions in both the carotid artery and the aorta. BSO decreased EDHF dependent relaxations only in the aorta. ACh-induced NO-dependent relaxations and augmented contractions were normalized by taurine. BSO increased TNF-α expressions in both carotid arteries and aortas, which were reversed by taurine. The BSO-induced increase in IL-1β was reversed by taurine only in aortae. Treatment with BSO resulted in vascular reactivity changes and increased immunostaining of TNF-α in mainly carotid arteries in this model of oxidative stress. The effect of taurine on BSO-induced vascular reactivity changes varied depending on the vessel. The inhibition of the increase in TNF-α expression by taurine in both carotid arteries and aortae supports the proposal that taurine has a beneficial effect in the treatment of inflammatory diseases such as atherosclerosis.

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

    Science.gov (United States)

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

    2009-01-01

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

  7. Do iatrogenic serosal injuries result in small bowel perforation in a rabbit model?

    Science.gov (United States)

    Tsai, M C; Candy, G; Costello, M A; Grieve, A D; Brand, M

    2017-06-01

    Surgical dogma dictates that serosal injuries should be repaired during laparotomy as these injuries may result in localised areas of bowel ischaemia and may perforate. No study has investigated whether there is a correlation between the extent of serosal injuries and the risk for perforation under normal physiological conditions. We hypothesized that small bowel serosal injuries do not result in early or late perforation at physiological intraluminal pressures regardless of their size. An in-vivo rabbit small bowel serosal injury model was developed and two experiments were conducted. The first - to determine whether and at which pressures various lengths and circumferences of serosal injuries in small bowel result in immediate bowel perforation - was performed infusing saline into isolated bowel segments with or without a variety of serosal injuries. In the second study - to determine whether or not serosal injuries result in delayed perforation - a range of injuries was created in rabbits and the effect assessed at re-laparotomy 5 days after the creation of the injury. No perforations were observed at the site of serosal injuries at physiological intraluminal pressures. Perforations occurred at 43.7+ 18.6 cmH₂O, 23.3+ 14.4 cmH₂O, and 24.4+ 23.9 cmH₂O for controls, 4 cm long and 100% circumference serosal injuries respectively (p-value = 0.18 for various lengths and 0.71 for various circumferences). No serosal injuries perforated within 72 or 120 hours after creation. Small bowel serosal injuries do not perforate or leak at physiological intraluminal pressures, either at the time of creation or up to 120 hours thereafter.

  8. Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

    Science.gov (United States)

    Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2017-03-01

    Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

  9. Use of a gel biopolymer for the treatment of eviscerated eyes: experimental model in rabbits

    Directory of Open Access Journals (Sweden)

    Francisco de Assis Cordeiro-Barbosa

    2012-08-01

    Full Text Available PURPOSE: To evaluate histologically the integration process of cellulose gel produced by Zoogloea sp when implanted into rabbits' eviscerated eyes. METHODS: This experimental study employed 36 eyes of 18 rabbits subjected to evisceration of their right eyes. The sclerocorneal bag was sutured and filled with biopolymer from sugar cane in the gel state. All animals were clinically examined by biomicroscopy until the day of their sacrifice which occurred on the 7th, 30th, 60th, 90th, 120th, or 240th day. The eyeballs obtained, including the left eyes considered controls were sent for histopathological study by optical macroscopy and microscopy. Tissue staining techniques used included hematoxylin-eosin, Masson trichrome (with aniline, Gomori trichrome, Van Gienson, Picrosirius red, and periodic acid-Schiff (PAS. RESULTS: No clinical signs of infection, allergy, toxicity, or extrusion were observed throughout the experiment. The corneas were relatively preserved. Macroscopic examination revealed a decrease of ~ 8% in the volume of the bulbs implanted with the biopolymer. After cutting, the sclerocorneal bag was solid, compact, elastic, and resistant to traction, with a smooth and whitish surface, and showed no signs of necrosis or liquefaction. The episcleral tissues were somewhat hypertrophied. The histological preparations studied in different colors revealed an initial lymphoplasmacytic infiltration, replaced by a fibroblastic response and proliferation of histiocytes, along with formation of giant cells. Few polymorphonuclearneutrophils and eosinophils were also found. Neovascularization and collagen deposition were present in all animals starting from day 30; although on the 240th day of the experiment the chronic inflammatory response, neovascularization and collagen deposition had not yet reached the center of the implant. CONCLUSION: In this model, the cellulose gel produced by Zoogloea sp proved to be biocompatible and integrated into the

  10. Effect of cyclic training model on terminal structure of rabbit Achilles tendon: an experimental study

    Directory of Open Access Journals (Sweden)

    Chang-lin HUANG

    2012-05-01

    Full Text Available Objective  To observe the effect of cyclic training on histomorphology of the terminal structure of rabbit Achilles tendon, and explore its preventive effect on training-based enthesiopathy. Methods  Seventy-two Japanese white rabbits were randomly assigned to four groups: control group, jumping group, running group and cyclic training group, 18 for each. Three rabbits of each group were sacrificed at the 2nd, 3rd, 4th, 6th, 8th and 10th week. The terminal insertion tissues of bilateral Achilles tendons were harvested from these rabbits for observing the pathomorphological changes under light microscope, and pathological scoring and statistical analysis were carried out. Results  Light microscopy showed that the tendon fibers and fibrocartilage in the Achilles tendon insertion region were severely damaged in the jumping group, and though the tendon fibers were damaged severely, the injury to the fibrocartilage was comparatively less serious in the running group. The injuries to the tendon fibers and fibrocartilage were milder in the cyclic training group than in the jumping group and running group. In the 2nd, 3rd, 4th, 6th and 8th week, the histopathology score of insertion of Achilles tendon was 1.17±0.12, 2.19±0.15, 3.23±0.20, 4.66±0.16, 4.71±0.18, 4.63±0.13 respectively in the jumping group, and 1.16±0.13, 1.15±0.14, 2.18±0.12, 2.99±0.15, 3.98±0.16, 4.01±0.12 respectively in the running group. Increase in pathological score appeared earlier in the jumping group than in the running group, and a significant increase began at the 3rd week. The difference in pathological score between the two groups originated mainly from the changes in the tidemark. In the 2nd, 3rd, 4th, 6th, 8th and 10th week, the pathological score of Achilles tendon insertion was 1.13±0.14, 1.16±0.17, 1.15±0.13, 2.18±0.13, 2.17±0.12, 2.92±0.11 respectively in the cyclic training group, and they showed no significant changes as compared with control

  11. Experimental model of severe acute pancreatitis in rabbits Modelo experimental de pancreatite aguda grave em coelhos

    Directory of Open Access Journals (Sweden)

    Alberto Goldenberg

    2007-10-01

    Full Text Available PURPOSE: To develop an experimental model of severe acute pancreatitis in rabbits through a pancreatic ductal injection of sodium taurocholate. METHODS: Twenty-four albino rabbits of the New Zealand lineage were distributed into four groups of six animals (A, B, C and S. The rabbits of three experimental groups (A, B and C were submitted to a laparatomy and received a pancreatic ductal injection of 1ml/kg sodium taurocholate 5%. Also, they were submitted to further laparatomies after 4h, 8h and 12h, respectively. The control group (S was subdivided into two groups of three animals: in subgroup S1 only the pancreatic duct catheterization was performed whereas in subgroup S2 the pancreatic duct catheterization as well as an injection of 1ml/kg physiologic solution 0.9% were carried out. After 12 hours, the rabbits were evaluated. In the re-intervention, blood was collected to determine the amylasemia and a pancreatectomy was carried out to investigate interstitial infiltration, steatonecrosis and necrosis of the organ, using an optical microscope. RESULTS: There was an elevation of amylase in all groups thus proving the existence of acute pancreatitis. The size of the interlobular septum increased progressively with a greater variation between group S1 (0.13 and group C (0. 53 (p=0.035. While all the animals in group A exhibited focal cellular necrosis, it was more intense in the rabbits of group B and culminated with a high proportion of severe pancreatic necrosis in group C animals. The difference in the intensity of cellular necrosis showed statistic significance (p=0.001. CONCLUSION: The proposed experimental model demonstrated its reproducibility and effectiveness in producing severe acute pancreatitis in rabbits.OBJETIVO: Desenvolver modelo experimental de pancreatite aguda grave em coelhos por meio da injeção de taurocolato de sódio no ducto pancreático. MÉTODOS: Vinte e quatro coelhos albinos da linhagem Nova Zelândia foram distribu

  12. [Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

    Science.gov (United States)

    Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

    2012-10-01

    This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

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

    Science.gov (United States)

    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.

  14. Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Sepsis induced acute lung injury (ALl) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALl. Methods Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n=7 in each group). After a tracheotomy had been performed, ALl was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 pg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution. Results In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68±0.06) ng/ml, vs APC group of (0.62±0.07) ng/ml at 6 hours, P<0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32±0.03) μg/ml at 2 hours, (2.24±0.06) μg/ml at 4 hours and (2.21±0.09) μg/ml at 6 hours, vs APC group (2.46±0.04) μg/ml at 2 hours, (2.40±0.05) pg/ml at 4 hours and (2.39±0.07) μg/ml at 6 hours, P<0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAl-1) both in plasma (control group was (0.68±0.12) ng/ml at 1 hour, (0.84±0.06) ng/ml at 2 hours, (0.87±0.08) ng/ml at 4 hours and (0.91±0.05) ng/ml at 6 hours, vs APC group (0.42±0.16) ng/ml at 1 hour, (0.43±0.04) ng/ml at 2 hours, (0.45±0.09) ng/ml at 4 hours and (0.45±0.14) ng/ml at 6 hours, P<0.01) and in bronchoalveolar lavage fluid (at 6 hours: sham, (1.05±0.05) ng/ml; control, (1.13±0.06) ng/ml; APC, (1.06±0.06) ng/ml; P<0.05). However, APC failed to prevent the decrease in PaO/FiO ratio. APC-treated rabbits

  15. Comparative Protein Structure Modeling Using MODELLER.

    Science.gov (United States)

    Webb, Benjamin; Sali, Andrej

    2016-06-20

    Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley & Sons, Inc.

  16. A Rabbit Model Study to Determine the Efficacy of a Prototype Corneal Endothelium Protector during Cataract Surgery

    Directory of Open Access Journals (Sweden)

    Annabel C. Y. Chew

    2017-01-01

    Full Text Available Purpose. We evaluated the efficacy and safety of a mechanical device, the P-chute, in corneal endothelium preservation during phacoemulsification in a rabbit model. Methods. Twenty-four rabbits were randomly assigned into 2 groups. One eye of each rabbit underwent phacoemulsification that simulated the removal of a dense nucleus, with or without the P-chute. Serial slit-lamp examinations, anterior segment optical coherence tomography (ASOCT scans, and specular microscopy were performed. Three rabbits from each group were sacrificed on postoperative days (PODs 1, 5, 7, and 14. Histological analysis of the corneas was performed. Results. There was a trend towards lesser endothelial cell loss for the P-chute group at POD1 (4.9% versus 12.5%, p=0.53, POD5 (10.4% versus 12.2%, p=0.77, and POD7 (10.5% versus 17.2%, p=0.52. There was no significant difference in the corneal thickness (p=>0.05 between the 2 groups. The insertion of the device was challenging. The use of the P-chute only added an extra 15% to the surgical time. Conclusions. There was a trend towards better endothelium preservation with the P-chute even though the results were not statistically significant. We believe that the device could be useful in certain surgical situations. Further work is needed to improve the device insertion.

  17. Systemic and local reactions of a water-soluble copolymer bone on a bony defect of rabbit model.

    Science.gov (United States)

    Lee, Tao-Chen; Chang, Nyuk-Kong; Su, Feng-Wen; Yang, Yu-Lin; Su, Thung-Ming; Lin, Yu-Jun; Lin, Wan-Ching; Huang, Hsiu-Yu

    2009-12-01

    Ostene, a synthetic water-soluble bone hemostatic agent, is commercially available. In the current study, we evaluated the systemic and local effects of this copolymer in a rabbit model. Eighteen rabbits underwent creation of a bony defect at right iliac crest. These rabbits were then evenly divided into 3 groups. In group 1, the defect surfaces were treated with bone wax; in group 2, the defect surfaces were treated with Ostene; in group 3, the defect surfaces were not treated with anything. Then, the animals underwent blood examinations, including WBC count, CRP, and ESR at 0, 1, 3, and 6 weeks, and were killed at 6 weeks for histologic examination. Another 6 rabbits (group 4) underwent the same surgical treatment of group 2 animals but had blood examinations of BUN and creatinine. The blood examinations showed that the WBC count, CRP, and ESR of all the animals in the first 3 groups were within normal limits in the postoperative periods. Microscopic examinations demonstrated residual bone wax and fibrotic tissue at the defect surfaces in group 1 animals. However, there was no Ostene at the defect surfaces in group 2 animals. The groups 2 and 3 animals showed no fibrotic tissue at the defect surfaces. The group 4 animals showed normal serum levels of BUN and creatinine in the postoperative periods. Ostene is absorbable and induces no systemic inflammation (including acute renal damage) and local inflammation in animal bodies.

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

    OpenAIRE

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

    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 obser...

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

    Science.gov (United States)

    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.

  20. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

    Institute of Scientific and Technical Information of China (English)

    Xiang-Ming Fang; Chun-Hong Hu; Xiao-Yun Hu; Xuan-Jun Yao; Ping-Yan Qian; Ju-Ying Zhou; Jian Guo

    2015-01-01

    Background:To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI) for the future investigation of computed tomography perfusion.Methods:A total of 72 New Zealand rabbits were randomly divided into two groups:36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α (TNF-a) and transforming growth factor-βl (TGF-β1) in local lung tissue was detected by immunohistochemistry.Results:(1) Radiation-induced lung injury occurred in all rabbits in the test group.(2) Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups (each P < 0.05).(3) Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters (each P < 0.05):thickness of alveolar wall,density of pulmonary interstitium area (1 h after radiation),number offibroblasts and fibrocytes in interstitium (24 h after radiation).The test group metrics also correlated well with the time ofpostradiation.(4) Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group (P < 0.005),with no significant differences in the control group (P > 0.05).At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05),correlating well with the time postradiation (r =0

  1. Biocompatibility of helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials in a rabbit corneal model.

    Science.gov (United States)

    Wang, Liqiang; Ma, Ruijue; Du, Gaiping; Guo, Huiling; Huang, Yifei

    2015-01-01

    Silk proteins represent a unique choice in the selection of biomaterials that can be used for corneal tissue engineering and regenerative medical applications. We implanted helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials into the corneal stroma of rabbits, and evaluated its biocompatibility. The corneal tissue was examined after routine hematoxylin-eosin staining, immunofluorescence for collagen I and III, and fibronectin, and scanning electron microscopy. The silk films maintained their integrity and transparency over the 180-day experimental period without causing immunogenic and neovascular responses or degradation of the rabbit corneal stroma. Collagen I increased, whereas Collagen III and fibronectin initially increased and then gradually decreased. The extracellular matrix deposited on the surface of the silk films, tightly adhered to the biomaterial. We have shown this kind of silk film graft has suitable biocompatibility with the corneal stroma and is an initial step for clinical trials to evaluate this material as a transplant biomaterial for keratoplasty tissue constructs.

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

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  4. Modelling of proteins in membranes

    DEFF Research Database (Denmark)

    Sperotto, Maria Maddalena; May, S.; Baumgaertner, A.

    2006-01-01

    This review describes some recent theories and simulations of mesoscopic and microscopic models of lipid membranes with embedded or attached proteins. We summarize results supporting our understanding of phenomena for which the activities of proteins in membranes are expected to be significantly ...

  5. The role of fine-scale anatomical structure in the dynamics of reentry in computational models of the rabbit ventricles.

    Science.gov (United States)

    Bishop, Martin J; Plank, Gernot

    2012-09-15

    Fine-scale anatomical structures in the heart may play an important role in sustaining cardiac arrhythmias. However, the extent of this role and how it may differ between species are not fully understood. In this study we used computational modelling to assess the impact of anatomy upon arrhythmia maintenance in the rabbit ventricles. Specifically, we quantified the dynamics of excitation wavefronts during episodes of simulated tachyarrhythmias and fibrillatory arrhythmias, defined as being respectively characterised by relatively low and high spatio-temporal disorganisation.Two computational models were used: a highly anatomically detailed MR-derived rabbit ventricular model (representing vasculature, endocardial structures) and a simplified equivalent model, constructed from the same MR-data but lacking such fine-scale anatomical features. During tachyarrhythmias, anatomically complex and simplified models showed very similar dynamics; however, during fibrillatory arrhythmias, as activation wavelength decreased, the presence of fine-scale anatomical details appeared to marginally increase disorganisation of wavefronts during arrhythmias in the complex model. Although a small amount of clustering of reentrant rotor centres (filaments) around endocardial structures was witnessed in follow-up analysis (which slightly increased during fibrillation as rotor size decreased), this was significantly less than previously reported in large animals. Importantly, no anchoring of reentrant rotors was visibly identifiable in arrhythmia movies. These differences between tachy- and fibrillatory arrhythmias suggest that the relative size of reentrant rotors with respect to anatomical obstacles governs the influence of fine-scale anatomy in the maintenance of ventricular arrhythmias in the rabbit. In conclusion, our simulations suggest that fine-scale anatomical features play little apparent role in the maintenance of tachyarrhythmias in the rabbit ventricles and, contrary to

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

    Science.gov (United States)

    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

  7. Overexpression of CDKN1B inhibits fibroblast proliferation in a rabbit model of experimental glaucoma filtration surgery.

    Science.gov (United States)

    Yang, Jian-gang; Deng, Ying; Zhou, Ling-xiao; Li, Xiao-yan; Sun, Peng-rui; Sun, Nai-xue

    2013-01-14

    To investigate the potential antiproliferative effect of cyclin-dependent kinase inhibitor 1B (CDKN1B) overexpression in a rabbit model of glaucoma filtration surgery (GFS). The recombinant adenovector expressing exogenous CDKN1B was delivered to Tenon's capsule by subconjunctival injection during unilateral filtration surgery. The time course of CDKN1B expression was monitored by immunohistochemistry and Western blot analysis. Evaluation of proliferating activity was performed by proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar organizing region (AgNOR) staining, and fibroblast-specific protein 1 (FSP-1). Cyclin-dependent kinase 2 (Cdk2) and Cdk4 expression were detected with immunohistochemical analysis. The overexpression of CDKN1B in Tenon's capsule was monitored throughout the experimental period. Immunoreactivity to CDKN1B was mainly observed in the nucleus of fibroblasts. The increased expression of CDKN1B in sclera was detected up to 21 days after viral infection, whereas the level of CDKN1B protein in corneal stroma was not significantly increased. The overexpression of CDKN1B induced a significant decrease in AgNOR number/nucleus and area/nucleus, PCNA staining, FSP-1 positive cells, and the decreased expressions of Cdk2 and Cdk4, as evidenced by nuclear and cytoplasmic immunoreactivity to Cdk2 and Cdk4 antibodies in positive fibroblasts. The persistent overexpression of CDKN1B mediated by the recombinant adenovector expressing exogenous CDKN1B in Tenon's fibroblasts after GFS may lead to the inhibition of fibroblast proliferation and the downregulation of Cdk2 and Cdk4 activity, thereby reducing the severity of scar formation and the surgical outcome.

  8. A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Pengfei Lei

    Full Text Available 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.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.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.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.

  9. Effects of joint contracture on the contralateral unoperated limb in a rabbit knee contracture model: a biomechanical and genetic study.

    Science.gov (United States)

    Abdel, Matthew P; Morrey, Mark E; Grill, Diane E; Kolbert, Christopher P; An, Kai-Nan; Steinmann, Scott P; Sanchez-Sotelo, Joaquin; Morrey, Bernard F

    2012-10-01

    In most animal models, unoperated contralateral limbs are used as controls. However, in some experimental circumstances, the contralateral limb may represent a skewed control. The main purpose of this study was to determine if the unoperated contralateral limb could be used as a control, or if a different unoperated animal's limb should be used instead. Seventeen rabbits were divided into two groups. Group 1 rabbits (n = 12) underwent surgery on their right limbs to induce a contracture. Group 2 rabbits (n = 5) underwent no surgery. The left non-operated limbs of rabbits in group 1 were biomechanically and genetically compared to the limbs of unoperated rabbits in group 2 with the use of a validated joint measuring device and custom microarray, respectively. After 8 weeks of immobilization, there was a statistically greater flexion contracture in the unoperated contralateral limbs compared to the limbs of animals that received no surgery(8.4 ± 8.9° vs. 0 ± 0°; p-value = 0.03). When animals were remobilized for an additional 16 weeks, the significance between groups was lost (11.9 ± 21.4° vs. 8.9 ± 9.5°; p = 0.38). Similarly, there was a statistically significant increase in nine genes at 8 weeks (p contracture at 8 weeks. After 16 weeks of remobilization, there is no biomechanical or genetic difference between contralateral non-operated limbs and limbs of animals not undergoing any surgical intervention. Given the biomechanical and genetic findings, the contralateral non-operated limb can be used as a valid control. Copyright © 2012 Orthopaedic Research Society.

  10. Bioevaluation study of 32P-CP-PLLA particle brachytherapy in a rabbit VX2 lung tumor model.

    Science.gov (United States)

    Xu, Yu ping; Yang, Min; Pan, Dong hui; Wang, Li zhen; Liu, Lu; Huang, Peilin; Shao, Guoqiang

    2012-04-01

    The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (pCP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  12. A longitudinal cross-over study of serum cholesterol and lipoproteins in rabbits fed on semipurified diets containing either casein or soybean protein

    NARCIS (Netherlands)

    Terpstra, A.H.M.; Woodward, C.J.H.; West, C.E.; Boven, van H.G.

    1982-01-01

    1. Two groups, each of six rabbits, were fed on semi-purified diets containing either 400 g casein or 400 g soya-bean protein/kg for 20 d and then the diets of the two groups were crossed-over. 2. Just before the cross-over, the serum cholesterol concentration (mean ± SE) was 3068 ± 592 and 800 ± 14

  13. Infliximab's influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model

    DEFF Research Database (Denmark)

    Frostberg, Erik; Ström, Petter; Gerke, Oke;

    2014-01-01

    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...

  14. Effect of a High Dose of Vitamin D on A Rabbit Model of Atherosclerosis

    National Research Council Canada - National Science Library

    Malek, H.A; Shata, A

    2014-01-01

    .... This work evaluates the effect of vitamin D on regression of atherosclerosis. Forty-eight male rabbits were divided into: Group Ia: [Standard diet + saline for 4 weeks]; Group I b: [Standard diet...

  15. Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal matrix hemorrhage

    National Research Council Canada - National Science Library

    Georgiadis, Paraskevi; Xu, Hongmin; Chua, Caroline; Hu, Furong; Collins, Lee; Huynh, Chau; Lagamma, Edmund F; Ballabh, Praveen

    2008-01-01

    .... We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries. About 80...

  16. Effect of anticoagulants and glucose on refractometric estimation of protein in canine and rabbit plasma.

    Science.gov (United States)

    Dubin, S; Hunt, P

    1978-10-01

    The effect of ethylenediaminetetraacetate (EDTA) compounds on the refractometric estimation of plasma protein concentration was attributed largely to osmotic fluid shifts, as reflected in changes in hematocrit, and to addition of total solids to the plasma. With H4EDTA, these two mechanisms were additive and caused increased plasma protein readings of significant magnitude even at recommended (1--2 mg/ml) anticoagulant concentrations. For the potassium and sodium salts, the two mechanisms were partly compensatory, which ameliorated the effect at 1--2 mg/ml concentration. At higher concentrations, such as might occur if a blood collecting tube were incompletely filled, all of the EDTA compounds caused technically significant over-estimation of plasma protein. When dextrose (d-glucose) was added in-vitro to canine blood, in amounts analogous to clinical hyperglycemia, the effect upon plasma protein estimation was minimal.

  17. The effect of substituting Nigella Sativa Meal as a source of protein in the rations of local rabbits on their productive performance and carcass traits

    Directory of Open Access Journals (Sweden)

    N. M. Abdullah

    2010-01-01

    Full Text Available Fifteen local male rabbits (6-8 weeks old were allocated into three nutritional groups. The first group fed standard ration, 5 and 10% of the Nigella Sativa Meal (NSM were added to the concentrated rations of the 2nd and 3rd groups replacing 36 and 72% of the soybean meal (SBM protein respectively. The feeding period lasted for eight weeks. Feed consumption and body weight gain were recorded weekly. At the end of feeding period, all rabbits were slaughtered and carcass traits were studied. No significant differences were found in total body weight gain and feed conversion rate (475, 502, 478 gm and (4.8, 4.8, 4.9 kg ration/1 kg wt. gain. Feed cost per 1 kg body gain declined 16% in the 3rd group, which cost 2294 ID, compared with the 1st group (2717 and the 2nd group (2561 ID. No significant differences in all carcass traits were found. Substituting 72% of SBM protein by NSM protein in rabbit ration showed no negative effects on all productive parameters and carcass traits.

  18. Wave front fragmentation due to ventricular geometry in a model of the rabbit heart

    Science.gov (United States)

    Rogers, Jack M.

    2002-09-01

    The role of the heart's complex shape in causing the fragmentation of activation wave fronts characteristic of ventricular fibrillation (VF) has not been well studied. We used a finite element model of cardiac propagation capable of simulating functional reentry on curved two-dimensional surfaces to test the hypothesis that uneven surface curvature can cause local propagation block leading to proliferation of reentrant wave fronts. We found that when reentry was induced on a flat sheet, it rotated in a repeatable meander pattern without breaking up. However, when a model of the rabbit ventricles was formed from the same medium, reentrant wave fronts followed complex, nonrepeating trajectories. Local propagation block often occurred when wave fronts propagated across regions where the Gaussian curvature of the surface changed rapidly. This type of block did not occur every time wave fronts crossed such a region; rather, it only occurred when the wave front was very close behind the previous wave in the cycle and was therefore propagating into relatively inexcitable tissue. Close wave front spacing resulted from nonstationary reentrant propagation. Thus, uneven surface curvature and nonstationary reentrant propagation worked in concert to produce wave front fragmentation and complex activation patterns. None of the factors previously thought to be necessary for local propagation block (e.g., heterogeneous refractory period, steep action potential duration restitution) were present. We conclude that the complex geometry of the heart may be an important determinant of VF activation patterns.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Reconstruction with autologous pasteurized whole knee joint I: experimental study in a rabbit model.

    Science.gov (United States)

    Ahmed, Adel Refaat; Watanabe, Hideomi; Takagishi, Kenji

    2003-01-01

    Hyperthermia-treated bone has been used for skeletal reconstruction after resection of malignant bone tumors, and more favorable results have been seen after pasteurization than after autoclaving or boiling. Pasteurization destroys malignant cells while preserving the bone-inducing property. All previous experimental models have studied replantation of bone segments, but reconstruction of joints is more important clinically. We studied the effects of extracorporeal hyperthermia on the reintegration of autologous whole knee joint grafts over a period of 16 weeks in a rabbit model. The whole knee joint was resected from 32 animals, heat-treated at 65 degrees C for 30 min, and replanted. In the control group, resection and replantation were performed without heat treatment. Reintegration was assessed by macroscopic analysis, histology, histochemistry, and radiography. Reintegration of the pasteurized group showed excellent remodeling during the 16 weeks, similar to the control groups. Responses to the pasteurization and the subsequent reintegration of cartilage, menisci, and ligaments were similar at 4, 8, 12, and 16 weeks with no significant difference between the two groups, although cartilage degradation seemed to occur earlier in the study group than in the control group. These results suggest that pasteurization may be superior to other cell-lethal treatments for autotransplantation of the whole joint currently available.

  2. An experimental study of using Chai Lai Prescription to treat in vitro rabbit models of reflux esophagitis

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hua; WEN Hao; YOU Si-hong; XU Xiao-fei; WEN Wei

    2013-01-01

    Background Chai Lai Prescription is a Chinese herbal compound which is used to sooth the liver,strengthen the spleen and harmonize the stomach for descending adverse Qi.We initiated the study to investigate its mechanism of treating in vitro rabbit reflux esophagitis models.Methods Adult male Japanese white rabbits,weighing 1.8-2.2 kg,were divided into five groups of three each,which were:normal control group (Krebs buffer,pH7.4),esophagitis model group (Krebs buffer,pH5.8),esophagitis model proup+low-dose Chinese herbal medicine protection group (0.6 mg·ml1·kg1),esophagitis model group+moderate-dose Chinese herbal medicine protection group (6 mg·ml1·kg1),esophagitis model group+high-dose Chinese herbal medicine protection group (60 mg·ml1·kg1).The RT-PCR method was used to test the influence of Chai Lai Prescription on IL-1 and IL-6 in in vitro rabbit models of esophagitis.We treated the in vitro models with different doses of Chinese herbal medicine.Results Esophageal mucosa were filled with various liquids.IL-6 and IL-1β mRNA expression was increased in rabbit esophageal mucosa stimulated with acid.Chinese herbal medicine significantly reduced the levels of IL-6 and IL-1β mRNA expression in the in vitro cultured rabbit esophageal mucosa.Using Chinese herbal medicine to treat in vitro models of RE,we found that the IL-6 and IL-1β mRNA expression levels went down,near to or lower than the normal control levels,compared with the group treated with acidified buffer solution.Conclusions Chai Lai Prescription lowered the IL-1β and IL-6 cytokine mRNA levels and protected the esophageal mucosa in the in vitro models of reflux esophagitis,suggesting that the traditional Chinese herbal compound may be able to treat reflux esophagitis by inhibiting the its inflammatory mediators.

  3. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First,control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber,and then hypodermic injection of domestic rhEP...

  4. Coarse-grain modelling of protein-protein interactions

    NARCIS (Netherlands)

    Baaden, Marc; Marrink, Siewert J.

    2013-01-01

    Here, we review recent advances towards the modelling of protein-protein interactions (PPI) at the coarse-grained (CG) level, a technique that is now widely used to understand protein affinity, aggregation and self-assembly behaviour. PPI models of soluble proteins and membrane proteins are separate

  5. Changes in gene expression and protein distribution at different stages of mechanically induced disc degeneration--an in vivo study on the New Zealand white rabbit.

    Science.gov (United States)

    Omlor, Georg W; Lorenz, Helga; Engelleiter, Karl; Richter, Wiltrud; Carstens, Claus; Kroeber, Markus W; Guehring, Thorsten

    2006-03-01

    The objective of the study was to improve the biological understanding of degenerative disc disease using a rabbit model in which different stages of disc degeneration are induced by variation of the duration of loading with an external compression-device applying 2.4 MPa. Gene expression and protein distribution were analyzed in controls and after 1, 28, and 56 days of hyperphysiologic loading. To evaluate extracellular matrix genes, quantitative real-time reverse-transcriptase polymerase chain reaction was applied for collagen I, collagen II, biglycan, decorin, fibromodulin, fibronectin, aggrecan, and osteonectin. As representatives of catabolic, anticatabolic, and anabolic factors, matrix metalloproteinase-13 (MMP-13), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and bone morphogenetic protein-2 (BMP-2) were chosen. To evaluate protein distribution, immunohistochemistry was performed for collagen I, collagen II, and BMP-2/4. Matrix gene expression was characterized by two major developments: collagen I and II, biglycan, and decorin showed early elevation followed by later downregulation to control levels, whereas fibromodulin, fibronectin, aggrecan, and osteonectin showed continuous upregulation or remained at similar levels. Induction of MMP-13 gene expression was found in degenerated discs. TIMP-1 and BMP-2 were elevated immediately after hyperphysiologic loading and presented highest levels in the 56-day group. Immunohistochemistry showed less collagen II and BMP-2/4 positive cells after compression. In conclusion, elevated matrix gene expression represents an early cellular response to hyperphysiologic loading. As degeneration progresses, some matrix genes increase upregulation, whereas others start downregulation. Continuous upregulation of catabolic, anticatabolic, and anabolic factors indicates their important role in the degeneration process. Copyright 2005 Orthopaedic Research Society.

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

    OpenAIRE

    LIU, Jiayi; Li, Ning; Li, Li; LI, DANYE; Liu, Kai; Zhao, Lingyun; TANG, JINTIAN; Li, Liya

    2013-01-01

    Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was s...

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

    Science.gov (United States)

    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.

  8. Long-term anodal block stimulation at sacral anterior roots promoted recovery of neurogenic bladder function in a rabbit model of complete spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Xiaoran Wang; Yongjie Wang; Jihu Lian; Chaoling Shi; Yao Wang; Li Fan; Qi Gao; Xiaoyu Yang; Weihua Wang; Xinquan Gu; Guifeng Liu; Peng Yan; Ge Gao; Xin Yu

    2012-01-01

    A complete spinal cord injury model was established in experimental rabbits using the spinal cord clip compression method. Urodynamic examination was performed 2 weeks later to determine neurogenic bladder status. The rabbits were treated with anodal block stimulation at sacral anterior roots for 4 weeks. Electrical stimulation of sacral anterior roots improved urodynamic parameters of neurogenic bladder in rabbit models of complete spinal cord injury, effectively promoted urinary function, and relieved urinary retention. Immunohistochemistry results showed that a balance was achieved among expression of muscarinic receptor subunits M2, M3, ATP-gated ion channel P2X3 receptors, and β2-adrenergic receptor, and nerve growth factor expression decreased. These results suggested that long-term sacral anterior root stimulation of anodal block could be used to treat neurogenic bladder in a rabbit model of complete spinal cord injury.

  9. Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model

    Directory of Open Access Journals (Sweden)

    Kai Liu

    2010-10-01

    Full Text Available Kai Liu1*, Guangqing Cao1*, Xiquan Zhang1, Ruifang Liu2, Weiwei Zou3, Shuming Wu11Departments of Cardiovascular Surgery, 2Anesthesia, Qilu Hospital of Shandong University, Jinan; 3The School of Pharmaceutical Science, Shandong University, Jinan, Shandong, People’s Republic of China; *Kai Liu and Guangqing Cao contributed equally to this work.Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP on neointimal hyperplasia in a rabbit vein graft model.Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15% was much lower than that in Group 2 (30.35 ± 2.69% and in Group 3 (33.86 ± 8.72%. By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 µg/10 mg 28 days after single drug perfusion.Conclusion: Pretreatment with intraluminal RAP

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

    Science.gov (United States)

    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

  11. Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model.

    Science.gov (United States)

    Kroeber, Markus; Unglaub, Frank; Guehring, Thorsten; Guegring, Thorsten; Nerlich, Andreas; Hadi, Tamer; Lotz, Jeffrey; Carstens, Claus

    2005-01-15

    An in vivo study on the rabbit lumbar spine model. Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order to stimulate disc regeneration. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated are needed. New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. After 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were reversible after 28 days of distraction. The disc thickness increased

  12. Role of protein kinase C signaling in collagen degradation by rabbit corneal fibroblasts cultured in three-dimensional collagen gels.

    Science.gov (United States)

    Nagano, Takashi; Hao, Ji-Long; Nakamura, Masatsugu; Nishida, Teruo

    2002-08-01

    To understand the mechanism of corneal ulceration by characterizing the intracellular signaling pathways that regulate collagen degradation by corneal fibroblasts cultured in three-dimensional type I collagen gels. Specifically, the potential roles of protein kinase C (PKC) and protein kinase A (PKA) in collagen degradation were investigated. Rabbit corneal fibroblasts were cultured in three-dimensional type I collagen gels for 24 hours in the presence of plasminogen and in the absence or presence of activators or inhibitors of PKC or PKA. Degradation of collagen fibrils was then evaluated by measurement of released hydroxyproline, and the production of matrix metalloproteinases (MMPs) was assessed by gelatin zymography and immunoblot analysis. The PKC activator phorbol 12-myristate 13-acetate (PMA) increased the extent of collagen degradation by corneal fibroblasts in a dose-dependent manner, with the maximal effect apparent at a concentration of 0.1 microM. The inactive analog 4alpha-PMA had no effect on collagen degradation. The PKC inhibitor H-7 reduced the extent of collagen degradation by corneal fibroblasts in the absence or presence of PMA. Phorbol 12-myristate 13-acetate also increased the production of proMMP-1, -3, and -9 by corneal fibroblasts, whereas H-7 inhibited this effect. Neither the PKA activators 8-bromo-cAMP, isobutylmethylxanthine, and forskolin nor the PKA inhibitor HA1004 affected collagen degradation by corneal fibroblasts. These results demonstrate that PKC plays an important role in collagen degradation by corneal fibroblasts in three-dimensional type I collagen gels, whereas PKA does not appear to participate in this process.

  13. Experimental atherosclerosis in rabbits on diets with milk fat and different proteins

    NARCIS (Netherlands)

    Hermus, R.J.J.

    1975-01-01

    In this thesis the literature about the pathogenesis of atherosclerosis has been reviewed. The various risk indicators for atherosclerosis are discussed and related to the theory about atherogenesis. A review of the influence of milk fat constituents and dietary proteins on serum lipids and atherosc

  14. Therapeutic effects of liposome-enveloped Ligusticum chuanxiong essential oil on hypertrophic scars in the rabbit ear model.

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    Full Text Available Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10% was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1, caspase-3 and -9, and transforming growth factor beta 1 (TGF-β(1. In addition, the scar elevation index (SEI was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β(1, MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.

  15. Efficacy of silk fibroin-nano silver against Staphylococcus aureus biofilms in a rabbit model of sinusitis.

    Science.gov (United States)

    Jia, Minghui; Chen, Zhongchun; Guo, Yongwei; Chen, Xin; Zhao, Xia

    2017-01-01

    Staphylococcus aureus biofilms contribute significantly to the recalcitrant nature of chronic rhinosinusitis. In previous studies, it has been shown that silk fibroin-nano silver solution can eliminate S. aureus biofilms in vitro, which suggests a potential role of this novel agent in the treatment of biofilm-associated diseases, such as sinusitis. The aim of this study was to investigate the efficacy of silk fibroin-nano silver solution as a topical anti-biofilm agent in a rabbit model of sinusitis. Biofilm-associated sinusitis models were established in 24 New Zealand White rabbits by gelatin sponge placement and S. aureus inoculation through a hole drilled into the anterolateral wall of the right maxillary sinus. After 4 weeks, indwelling catheters were placed into the maxillary sinus. Different concentrations of silk fibroin-nano silver solution or normal saline were irrigated slowly into the maxillary sinus via the indwelling catheters. After 7 days of irrigation, the rabbits were sacrificed. The sinus mucosa was harvested and examined for biofilm biomass as well as morphological integrity of the epithelium by scanning electron microscopy. Silk fibroin-nano silver solution was found to be most effective in reducing the biomass of the S. aureus biofilms at a concentration of 384 mg/L, followed by the concentration of 153.6 mg/L, when compared with saline. After treatment with 384 mg/L silk fibroin-nano silver solution, the biofilms were completely eliminated and the injured epithelium was almost restored with regenerated cilia on the surface. Silk fibroin-nano silver solution was found to be an effective topical agent against S. aureus biofilms in the rabbit model of sinusitis, and its effect was concentration-dependent.

  16. Blocking collagen fibril formation in injured knees reduces flexion contracture in a rabbit model.

    Science.gov (United States)

    Steplewski, Andrzej; Fertala, Jolanta; Beredjiklian, Pedro K; Abboud, Joseph A; Wang, Mark L Y; Namdari, Surena; Barlow, Jonathan; Rivlin, Michael; Arnold, William V; Kostas, James; Hou, Cheryl; Fertala, Andrzej

    2017-05-01

    Post-traumatic joint contracture is a frequent orthopaedic complication that limits the movement of injured joints, thereby severely impairing affected patients. Non-surgical and surgical treatments for joint contracture often fail to improve the range of motion. In this study, we tested a hypothesis that limiting the formation of collagen-rich tissue in the capsules of injured joints would reduce the consequences of the fibrotic response and improve joint mobility. We targeted the formation of collagen fibrils, the main component of fibrotic deposits formed within the tissues of injured joints, by employing a relevant rabbit model to test the utility of a custom-engineered antibody. The antibody was delivered directly to the cavities of injured knees in order to block the formation of collagen fibrils produced in response to injury. In comparison to the non-treated control, mechanical tests of the antibody-treated knees demonstrated a significant reduction of flexion contracture. Detailed microscopic and biochemical studies verified that this reduction resulted from the antibody-mediated blocking of the assembly of collagen fibrils. These findings indicate that extracellular processes associated with excessive formation of fibrotic tissue represent a valid target for limiting post-traumatic joint stiffness. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1038-1046, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Evaluation of machining methods for trabecular metal implants in a rabbit intramedullary osseointegration model.

    Science.gov (United States)

    Deglurkar, Mukund; Davy, Dwight T; Stewart, Matthew; Goldberg, Victor M; Welter, Jean F

    2007-02-01

    Implant success is dependent in part on the interaction of the implant with the surrounding tissues. Porous tantalum implants (Trabecular Metal, TM) have been shown to have excellent osseointegration. Machining this material to complex shapes with close tolerances is difficult because of its open structure and the ductile nature of metallic tantalum. Conventional machining results in occlusion of most of the surface porosity by the smearing of soft metal. This study compared TM samples finished by three processing techniques: conventional machining, electrical discharge machining, and nonmachined, "as-prepared." The TM samples were studied in a rabbit distal femoral intramedullary osseointegration model and in cell culture. We assessed the effects of these machining methods at 4, 8, and 12 weeks after implant placement. The finishing technique had a profound effect on the physical presentation of the implant interface: conventional machining reduced surface porosity to 30% compared to bulk porosities in the 70% range. Bone ongrowth was similar in all groups, while bone ingrowth was significantly greater in the nonmachined samples. The resulting mechanical properties of the bone implant-interface were similar in all three groups, with only interface stiffness and interface shear modulus being significantly higher in the machined samples.

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

    Science.gov (United States)

    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.

  19. MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Strouse, P.J.; DiPietro, M.A.; Teo, E.L.H.J. [Section of Pediatric Radiology, University of Michigan Health System, Ann Arbor, MI (United States); Londy, F. [Division of Magnetic Resonance Imaging, Department of Radiology, University of Michigan Health System, Ann Arbor, MI (United States); Chrisp, C.E. [Unit of Laboratory Animal Medicine, University of Michigan Health System, Ann Arbor, MI (United States); Doi, K. [Division of Musculoskeletal Radiology, University of Michigan Health System, Ann Arbor, MI (United States)

    1999-05-01

    Background. Literature on magnetic resonance imaging (MR) evaluation of inflammatory joint effusions is sparse. Objective. To describe an animal model for studying infectious and non-infectious joint effusions with magnetic resonance imaging. Materials and methods. Ten rabbit knees with septic arthritis and four with talc synovitis were imaged with MR. Contralateral knees injected with saline served as controls. Fat saturation T2-weighted and gadolinium-enhanced T1-weighted images were assessed for joint effusion, and periarticular and adjacent intraosseous increased signal or enhancement. Each knee was cultured and underwent pathologic examination. Results. Both Staphylococcus aureus and talc produced effusions in all knees. The degree of periarticular signal and enhancement was greater in infected knees than talc-injected knees. No abnormal enhancement was seen within bone. Pathologic examination showed a greater degree of inflammation and joint destruction in the infected knees, but no evidence of osteomyelitis. Conclusion. A greater degree of abnormal signal and enhancement seen on MR suggests a more vigorous inflammatory process, as seen with septic arthritis. In spite of advanced septic arthritis, no enhancement was evident within bone, suggesting that enhancement within bone is not an expected finding in isolated septic arthritis and should raise concern for osteomyelitis. (orig.) With 3 figs., 15 refs.

  20. Early neonatal echocardiographic findings in an experimental rabbit model of congenital diaphragmatic hernia

    Directory of Open Access Journals (Sweden)

    P.H. Manso

    2015-03-01

    Full Text Available This study aimed to demonstrate that congenital diaphragmatic hernia (CDH results in vascular abnormalities that are directly associated with the severity of pulmonary hypoplasia and hypertension. These events increase right ventricle (RV afterload and may adversely affect disease management and patient survival. Our objective was to investigate cardiac function, specifically right ventricular changes, immediately after birth and relate them to myocardial histological findings in a CDH model. Pregnant New Zealand rabbits underwent the surgical procedure at 25 days of gestation (n=14. CDH was created in one fetus per horn (n=16, and the other fetuses were used as controls (n=20. At term (30 days, fetuses were removed, immediately dried and weighed before undergoing four-parameter echocardiography. The lungs and the heart were removed, weighed, and histologically analyzed. CDH animals had smaller total lung weight (P<0.005, left lung weight (P<0.005, and lung-to-body ratio (P<0.005. Echocardiography revealed a smaller left-to-right ventricle ratio (LV/RV, P<0.005 and larger diastolic right ventricle size (DRVS, P<0.007. Histologic analysis revealed a larger number of myocytes undergoing mitotic division (186 vs 132, P<0.05 in CDH hearts. Immediate RV dilation of CDH hearts is related to myocyte mitosis increase. This information may aid the design of future strategies to address pulmonary hypertension in CDH.

  1. Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model.

    Science.gov (United States)

    Glazer, Evan S; Zhu, Cihui; Hamir, Amir N; Borne, Agatha; Thompson, Catherine Shea; Curley, Steven A

    2011-12-01

    There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy.

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

    Science.gov (United States)

    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.

  3. 构建单纯烟熏至慢性阻塞性肺疾病兔模型%Establishment of a Rabbit Model of Smoke-induced Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    王培培; 邢珍; 刘全乐; 王锦川; 焦宝良; 王新生; 刘军超; 李福龙

    2012-01-01

    objective: To establishment of a rabbit model of smoke-induced chronic obstructive pulmonary disease. Methods: Cut tobacco was used as irritant to prepare chronic obstructive pulmonary disease models, Those rabbits in smoke—induced model group were in self-made smoke cage, Pure cut tobacco 15g was burned at a time. Those rabbits in normal control group were not exposed to smoke. Exposed to smoker for 0.5 hour once, 2 times per day, lasted for 70 days. All rabbits were anesthetized at no smoking for 1 week after the last smoke exposure , the arterial blood gases were analyzed before being sacrificed. Protein content in right lung bronchoalveolar lavage fluid (BALF) was measured and leukocyte count and classification were also done. The removed left lung tissues were stained with hematoxylin—eosin for histomorphology observation. Results: Totally 11 rabbits were involved in the analysis. When compared with normal control group, in smoke—induced model group, there were plenty of inflammatoty cells infiltrated in bronchial walls. Protein content and total mumber of leukocytes in BALF were increased significantly (p<0.05); P02 and SaO2 were significantly lower (p<0.05), PCO2 were significantly higher (p<0.05). Conclusion: A smoke—induced chronic obstructive pulmonary disease rabbit model was established successfully,and it should endure a long time one—lung ventilation after beihg anesthetized.%目的:构建烟熏至慢性阻塞性肺疾病兔模型.方法:利用自制的方法采用单纯旱烟烟熏兔70 d停1周,麻醉后行血气分析,处死后右肺进行支气管灌洗液分析,左肺作病理切片.结果:与正常饲养兔相比,烟熏兔肺泡灌洗液中蛋白含量显著增加,白细胞总数显著增加,分类中中性粒细胞比例增加:动脉氧分压(PO2)明显降低(P<0.05),二氧化碳分压(PCO2)增高(P<0.05),动脉血氧饱和度明显下降(P<0.05).结论:自制方法成功构建慢性阻塞性肺疾病兔模型,并能耐受麻

  4. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model.

    Science.gov (United States)

    Fisher, John P; Lalani, Zahid; Bossano, Carla M; Brey, Eric M; Demian, Nagi; Johnston, Carol M; Dean, David; Jansen, John A; Wong, Mark E K; Mikos, Antonios G

    2004-03-01

    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion. To test this hypothesis, healing bone was investigated within a rabbit incisor extraction socket, a subcritical size bone defect that resists significant soft tissue invasion by virtue of its conformity. After removal of the incisor teeth, one tooth socket was left as an empty control, one was filled with crosslinked polymer networks formed from the hydrophobic polymer poly(propylene fumarate) (PPF), and one was filled with a hydrogel formed from the hydrophilic oligomer oligo(poly(ethylene glycol) fumarate) (OPF). At five different times (4 days as well as 1, 2, 4, and 8 weeks), jaw bone specimens containing the tooth sockets were removed. We analyzed bone healing by histomorphometrical analysis of hematoxylin and eosin stained sections as well as immunohistochemically stained sections. The proposed hypothesis, that a hydrophilic material would hinder bone healing, was supported by the histomorphometrical results. In addition, the immunohistochemical results reflect molecular signaling indicative of the early invasion of platelets, the vascularization of wound-healing tissue, the differentiation of migrating progenitor cells, and the formation and remodeling of bone tissue. Finally, the results emphasize the need to consider biomaterial properties and their differing effects upon endogenous growth factors, and thus bone healing, during the development of tissue engineering devices. Copyright 2003 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

  6. Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Yin, Li-Yan; Calhoun, Jason H; Thomas, Jacob K; Shapiro, Stuart; Schmitt-Hoffmann, Anne

    2008-05-01

    The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.

  7. Acute radiation hypotension in the rabbit: a model for the human radiation shock syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Makale, M.T.

    1987-01-01

    This study has shown that total body irradiation (TBI) of immature rabbits leads to an acute fall in mean arterial pressures (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 temperatures, 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%.

  8. The Effect of Electroacupuncture on the Extracellular Matrix Synthesis and Degradation in a Rabbit Model of Disc Degeneration

    Directory of Open Access Journals (Sweden)

    Guo-fu Huang

    2014-01-01

    Full Text Available The present study was aimed at determining if the electroacupuncture (EA is able to protect degenerated disc in vivo. New Zealand white rabbits (n=40 were used for the study. The rabbits were randomly assigned to four groups. EA intervention was applied to one of the four groups. Magnetic resonance imaging and Pfirrmann’s classification were obtained for each group to evaluate EA treatment on the intervertebral disc degeneration. Discs were analyzed using immunofluorescence for the labeling of collagens 1 and 2, bone morphogenetic protein-2 (BMP-2, matrix metalloproteinase-13 (MMP-13, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1. For protein expression analysis, western blot was used for biglycan and decorin. Outcomes indicated that EA intervention decreased the grades compared with the compressed disc. Immunofluorescence analysis showed a significant increase of collagens 1 and 2, TIMP-1, and BMP-2 positive cells, in contrast to MMP-13 after EA treatment for 28 days. The protein expression showed a sign of regeneration that decorin and biglycan were upregulated. It was concluded that EA contributed to the extracellular matrix (ECM anabolic processes and increased the ECM components. MMPs and their inhibitors involved in the mechanism of EA intervention on ECM decreased disc. It kept a dynamic balance between ECM synthesis and degradation.

  9. Biodegradable beta-Tri-Calciumphosphate/hydroxyethyl methacrylate enhanced three component bone adhesive demonstrates biocompatibility without evidence of systemic toxicity in a rabbit model.

    Science.gov (United States)

    Bauer, Natali B; Brinke, Nina; Heiss, Christian; Skorupa, Agnes B; Peters, Fabian; Kraus, Ralf; Schnettler, Reinhard; Moritz, Andreas

    2009-08-01

    Bone gluing is an attractive surgical technique; however, its use in patients is hampered by a variety of side effects. Therefore, it was the aim of this ethically approved study to evaluate a novel biodegradable beta-Tri-Calciumphosphate (beta-TCP, Cerasorb)-enhanced bone adhesive regarding its toxicity and biocompatibility in a rabbit model. Fifty healthy New Zealand White rabbits were assigned in the study (n = 21) and sham-operated control group (n = 29). In the study group, a cylindrical part (4.6 x 10.0 mm) of the proximal tibia and distal femur was removed, reimplanted, and bone adhesive was applied. Blinded physical examination and sampling for hematology, clinical chemistry, and acute phase proteins (haptoglobin, C-reactive protein (CRP)) was performed before surgery and after 12, 24, 48, 72, 240, and 504 h. Significant findings of the physical examination included a slightly higher grading of warmth (p = 0.0019) and pain (p < 0.0001) of the wound 240 h after surgery in the study group. No significant differences between albumin, haptoglobin, CRP, and urea concentrations in both groups were evident, whereas the study group demonstrated significantly lower leukocyte count, total protein, and globulin concentrations (p < 0.0001). As expected, both groups showed a marked transient increase in muscle enzymes (Creatine Kinase and Aspartate Aminotransferase) following the surgery (p < 0.0001). Twelve to 24 h after surgery, a significant decrease in ionized calcium from 1.38 +/- 0.12 mmol/L to 1.06 +/- 0.13 mmol/L was noted in the study group (p < 0.0001). The results clearly indicated that the novel beta-TCP-enhanced bone adhesive showed good biocompatibility without significant evidence of acute or subacute local or systemic toxicity.

  10. Involvement of necroptosis, a newly recognized cell death type, in steroid-induced osteonecrosis in a rabbit model

    Science.gov (United States)

    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

  11. Noxious electrical stimulation of the pelvic floor and vagina induces transient voiding dysfunction in a rabbit survival model of pelvic floor dystonia

    OpenAIRE

    Dobberfuhl, Amy D.; Spettel, Sara; Schuler, Catherine; Levin, Robert M.; Dubin, Andrew H.; De, Elise J.B.

    2015-01-01

    Purpose Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior. Materials and Methods Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetan...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wen, E-mail: wenzhangxiao@126.com; Yan, Zhiping, E-mail: Yan.zhiping@zs-hospital.sh.cn; Luo, Jianjun, E-mail: luo.jianjun@zs-hospital.sh.cn; Fang, Zhuting, E-mail: 470389481@qq.com; Wu, Linlin, E-mail: linlinzhifubao@126.com; Liu, QingXin, E-mail: liu.qingxin@zs-hospital.sh.cn; Qu, Xudong, E-mail: qu.xudong@zs-hospital.sh.cn; Liu, Lingxiao, E-mail: liu.lingxiao@zs-hospital.sh.cn; Wang, Jianhua, E-mail: wang.jianhua@zs-hospital.sh.cn [Fudan University, Department of Interventional Radiology, Zhongshan Hospital (China)

    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

  13. Correspondence of CT perfusion imaging to pathological manifestations in rabbit models of hyperacute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Mingwu Lou; Yi Fan; Lizhong Jia; Weidong Hu; Yan Teng; Guangfu Yang

    2007-01-01

    BACKGROUND: Could the infarction be diagnosed quickly and accurately at the acute stage by CT perfusion imaging (CTPI) technology? Whether the images of CTPI will correspond with the pathological changes or not? All the questions need to be solved by experimental and clinical studies.OBJECTIVE: To reveal the rules of perfusion map changes and guide the early diagnosis of hyperacute cerebral infarction by analyzing the correlation of CTPI with pathological manifestations for hyperacute cerebral infarction.DESIGN: A randomized controlled animal experiment.SETTING: Experimental Center of Medical Radiology, Longgang Central Hospital of Shenzhen City.MATERIALS: Forty-two adult New Zealand rabbits of (2.6±0.5) kg, either male or female, were randomly divided into experimental group (n =36) and control group (n =6). Six rabbits in the experimental group were observed after ischemia for 0.5, 1, 2, 3, 4 and 6 hours respectively, and 1 rabbit in the control group was observed at each corresponding time point.METHODS: The experiments were carded out in the Experimental Center of Medical Radiology,Longgang Central Hospital of Shenzhen City from March 2003 to July 2004, Rabbit models of cerebral scanned at 0.5, 1, 2, 3, 4 and 6 hours after ischemia respectively. The dynamic CT scan slice was 13 mm from the anterior edge of the frontal cortex, and six fake color functional images were obtained, including cerebral blood flow map (CBF map), cerebral blood volume map (CBV map), peak to enhancement map (PE map),flow without vessels map, time to peak map (TP map), time to start map (TS map). The manifestations and (ROI) were drawn separately on the CBF map, CBV map, TP map and TS map. The blood flow parameters of focal and contralateral cerebral tissues could be obtained to calculate relative cerebral blood flow (rCBF,rCBF=focal CBF/contralateral CBF), relative cerebral blood volume (rCBV, rCBV= focal CBV/contralateral CBV), a relative time to peak (rTP, rTP= focal TP

  14. Biomechanical and radiographic comparison of demineralized bone matrix, and a coralline hydroxyapatite in a rabbit spinal fusion model.

    Science.gov (United States)

    Dodds, Robert A; York-Ely, Amanda M; Zhukauskas, Rasa; Arola, Travis; Howell, John; Hartill, Caroline; Cobb, Ronald R; Fox, Casey

    2010-09-01

    The use of bone grafts is an essential component in spinal fusion. Autologous bone has been shown to result in long-term stable arthrodesis between spinal motion segments. However, autograft can be associated with significant morbidity and a limited supply. Alternatives, such as allogeneic demineralized bone matrix (DBM), are a potential source and supplement to autograft bone. The current study compares the ability of a DBM product (BioSet RT) and a coralline hydroxyapatite (Pro Osteon 500R), for inducing spinal fusion in a rabbit model. BioSet RT, alone or in combination with autograft, and Pro Osteon 500R were implanted in the posterior lateral inter-transverse process region of the rabbit spine. The spines were evaluated at 18 weeks for fusion of the L4-L5 transverse processes using a total of 33 skeletally mature male rabbits; 4 naïve animals were also included in the study. Samples were evaluated radiographically, histologically, by palpation, and through mechanical strength testing. Radiographical, histological, and palpation measurements demonstrated the ability of BioSet RT to induce new bone formation and bridging fusion comparable to autograft. This material performed well alone or in combination with autograft material. Despite significantly higher biomechanical testing results, minimal bone formation and fusion was recorded for the Pro Osteon 500R-treated group. This in vivo study demonstrates the ability of BioSet RT to induce new bone formation, and there was a clear relationship between bridging bone and mechanical strength.

  15. The effect of subconjunctival bevacizumab on corneal neovascularization, inflammation and re-epithelization in a rabbit model

    Directory of Open Access Journals (Sweden)

    Glauco Reggiani Mello

    2011-01-01

    Full Text Available PURPOSE: To evaluate the use of subconjunctival bevacizumab on corneal neovascularization in an experimental rabbit model for its effect on vessel extension, inflammation, and corneal epithelialization. METHODS: In this prospective, randomized, blinded, experimental study, 20 rabbits were submitted to a chemical trauma with sodium hydroxide and subsequently divided into two groups. The experimental group received a subconjunctival injection of bevacizumab (0.15 m; 3.75 mg, and the control group received an injection of 0.15 ml saline solution. After 14 days, two blinded digital photograph analyses were conducted to evaluate the inflammation/diameter of the vessels according to pre-established criteria. A histopathological analysis of the cornea evaluated the state of the epithelium and the number of polymorphonuclear cells. RESULTS: A concordance analysis using Kappa's statistic showed a satisfactory level of agreement between the two blinded digital photography analyses. The neovascular vessel length was greater in the control group (p<0.01 than in the study group. However, the histopathological examination revealed no statistically significant differences between the groups in terms of the state of the epithelium and the number of polymorphonuclear cells. CONCLUSIONS: Subconjunctival bevacizumab inhibited neovascularization in the rabbit cornea. However, this drug was not effective at reducing inflammation. The drug did not induce persistent corneal epithelial defects.

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

    Science.gov (United States)

    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.

  17. Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

    Institute of Scientific and Technical Information of China (English)

    YOU Binquan; PU Jun; LIU Nian; YU Ronghui; RUAN Yanfei; LI Yang; WANG Lin

    2005-01-01

    To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

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

    Science.gov (United States)

    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  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.

  19. Histopathological comparison of bone healing effects of endonasal and percutaneous lateral osteotomy methods in rabbit rhinoplasty model.

    Science.gov (United States)

    Öğreden, Şahin; Rüzgar, Sedat; Tansuker, Hasan Deniz; Taşkın, Ümit; Alimoğlu, Yalçın; Aydın, Salih; Oktay, Mehmet Faruk; İzol, Uğur

    2017-07-17

    Lateral osteotomy is mainly performed either endonasally or percutaneously in rhinoplasty which is a frequently performed operation for the correction of nasal deformities. Both techniques have both advantages and disadvantages relative to each other. The aim of this study was to compare the histopathological effects of endonasal and percutaneous osteotomy techniques performed in rhinoplasty on bone healing and nasal stability in an experimental animal model. Eight one year-old New Zealand white rabbits were included. Xylazine hydrocloride and intramuscular ketamine anesthesia were administered to the rabbits. Endonasal osteotomy (8 bones) was performed in Group 1 (n=4), and percutaneous osteotomy (8 bones) in Group 2 (n=4). One month later the rabbits were sacrificed. Bone healing of the rabbits was staged according to the bone healing score of Huddleston et al. In both groups, nasal bone integrity was assessed subjectively. In the percutaneous osteotomy group, Grade 1 bone healing was observed in two samples (25%), Grade 2 bone healing in two samples (25%), Grade 3 bone healing in four samples (50%). In the endonasal osteotomy group, Grade 1 bone healing was observed in 6 samples (75%) and Grade 2 bone healing was observed in 2 samples (25%). In the percutaneous group, fibrous tissue was observed in 2, predominantly fibrous tissue and a lesser amount of cartilage was observed in 2 and an equal amount of fibrous tissue and cartilage was observed in 4 samples. In the endonasal group, fibrous tissue was observed in 6 samples, and predominantly fibrous tissue with a lesser amount of cartilage was observed in 2 samples. In both groups, when manual force was applied to the nasal bones, subjectively the same resistance was observed. Percutaneous lateral osteotomy technique was found to result in less bone and periost trauma and better bone healing compared to the endonasal osteotomy technique. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia

  20. In vivo laser cartilage reshaping with carbon dioxide spray cooling in a rabbit ear model: a pilot study.

    Science.gov (United States)

    Kuan, Edward C; Hamamoto, Ashley A; Sun, Victor; Nguyen, Tony; Manuel, Cyrus T; Protsenko, Dmitry E; Wong, Brian J F; Nelson, J Stuart; Jia, Wangcun

    2014-12-01

    Similar to conventional cryogen spray cooling, carbon dioxide (CO2) spray may be used in combination with laser cartilage reshaping (LCR) to produce cartilage shape change while minimizing cutaneous thermal injury. Recent ex vivo evaluation of LCR with CO2 cooling in a rabbit model has identified a promising initial parameter space for in vivo safety and efficacy evaluation. This pilot study aimed to evaluate shape change and cutaneous injury following LCR with CO2 cooling in 5 live rabbits. The midportion of live rabbit ears were irradiated with a 1.45 µm wavelength diode laser (12 J/cm(2)) with simultaneous CO2 spray cooling (85 millisecond duration, 4 alternating heating/cooling cycles per site, 5 to 6 irradiation sites per row for 3 rows per ear). Experimental and control ears (no LCR) were splinted in the flexed position for 30 days following exposure. A total of 5 ears each were allocated to the experimental and control groups. Shape change was observed in all irradiated ears (mean 70 ± 3°), which was statistically different from control (mean 37 ± 11°, P = 0.009). No significant thermal cutaneous injury was observed, with preservation of the full thickness of skin, microvasculature, and adnexal structures. Confocal microscopy and histology demonstrated an intact and viable chondrocyte population surrounding irradiated sites. LCR with CO2 spray cooling can produce clinically significant shape change in the rabbit auricle while minimizing thermal cutaneous and cartilaginous injury and frostbite. This pilot study lends support for the potential use of CO2 spray as an adjunct to existing thermal-based cartilage reshaping modalities. An in vivo systematic evaluation of optimal laser dosimetry and cooling parameters is required. © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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 (R(2) = 0.67, P < 0.001). MRE imaging has the potential to serve as a noninvasive, unenhanced imaging technique for liver fibrosis diagnosis and staging.

  2. [Phosphatase and tensin homolog deleted on chromosome ten/phosphatidyl Inositol 3-kinase/vascular endothelial growth factor signaling pathway changes in the rabbit Kawasaki disease model].

    Science.gov (United States)

    Niu, L; Fu, M Y; Tian, J; He, X H; Zhang, H N; Wang, Q W; Wang, Y; Li, C L; Wang, Z Z; An, X J

    2016-03-01

    To observe the changes of phosphatase and tensin homolog deleted on chromosome ten(PTEN)/ phosphatidyl Inositol 3-kinase(PI3K)/ vascular endothelial growth factor(VEGF)signaling pathway in a rabbit Kawasaki disease model. Model of Kawasaki disease was established in weanling Japanese big-eared rabbits with 10% bovine serum venous injection (2.5 ml/kg, 2 times, and 2 week's interval) through the ear. Twenty four rabbits were divided into 4 groups: control group (without injection of 10% bovine serum albumin, six rabbits); 1 day group (sacrificed a the second day after the establishment of Kawasaki disease models, six rabbits); 7 day group (sacrificed at the seventh day after establishment of Kawasaki disease model, six rabbits); 30 day group (sacrificed at the thirtieth day after establishment of Kawasaki disease model, six rabbits). Pathological analysis was performed on coronary artery tissue samples. The express of PTEN and PI3K were detected by immunohistochemistry. The levels of VEGF and CK were also examined with ELISA and white blood cells were counted. (1) Coronary artery of model groups was thinner, distorted and had enlarged lumen. (2) PTEN expression in 1 d group, 7 d group and 30 d group were 58.5 ± 12.9, 73.2±9.9 and 109.6 ± 24.4, respectively, significantly higher than in the control group (25.5 ± 6.9, P0.05) and significantly lower than 1 d and 7 d group (both P0.05). (6)White blood cell count were significantly higher in 1 d group, 7 d group and 30 d group than in control group (all PKawasaki disease model and the signaling pathway might be involved in this model.

  3. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

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

    Science.gov (United States)

    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.

  5. MR DIFFUSION WEIGHTED IMAGING FOR EVALUATION OF RADIOTHERAPEUTIC EFFECTS ON RABBIT VX2 TUMOR MODEL

    Institute of Scientific and Technical Information of China (English)

    Shuo Li; Hua-dan Xue; Xin-hai Wang; Fei Sun; Bo Jiang; Dong Liu; Jing Lei; Zheng-yu Jin

    2008-01-01

    Objective To investigate the feasibility of magnetic resonance (MR) diffusion weighted imaging (DWI) for evaluation of radiotherapeutic effects on rabbit VX2 tumor model.Methods Sixteen New Zealand white rabbits received a subcutaneous implantation of VX2 tumor cdl suspension 0.5 mL (4× 107cells/mL) in their right thighs to set up tumor model. And 2 weeks later they were randomly divided into therapy group (Group T, n = 10) and control group (Group C, n = 6). Group T received radiotherapy at a single dose of 10 Gy. MR imaging (MRI) scan including short TI inversion recovery echo-planar imaging DWI, T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequences were performed 1 day prior to as well as 1 day, 2 days, 3 days and 7 days after radiotherapy. Group C received only MRI scan at the same time points without any treatment. MRI appearance on T2WI, T1WI, and DWI images was compared and tumor volume was calculated. Apparent diffusion coefficient (ADC) values of the tumor were evaluated in all cases. HE staining was used for pathological study.Results Necrosis (n = 8) and hemorrhage (n = 2) were seen gradually on T2WI and T1WI images of Group T after time point of day 2 after irradiation. In Group C, no obvious necrosis was found until day 7. There was no significant difference in tumor volume between the two groups before radiotherapy. After radiotherapy, tumors in Group T showed a gradual growth but not as obvious as Group C. There was a significant difference in tumor volume between the two groups from day 2 on (P < 0.05). ADC value changed dramatically right from the 1st day after radio-therapy in Group T [(0.99 ± 0.15) ×10-3 mm2/s for 1 day before radiotherapy, (1.23 ± 0.08) ×10-3 , (1.45 ± 0.07) ×10-3 , (1.63 ± 0.06) ×10-3 , and (2.02 ± 0.18) ×10-3 mm2/s for day 1, 2, 3, and 7]; and ADC value had no significant changes after radiotherapy in Group C except day 7 [(1.07 ± 0.08) ×10-3 mm2/s for 1 day before radiotherapy, (1.03 ± 0.04) ×10

  6. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M;

    2000-01-01

    BACKGROUND: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human...

  7. Sulfanegen Sodium Treatment in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    Science.gov (United States)

    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.

    2010-01-01

    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. PMID:20705081

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Sung; Kim, Bok Yeol; Choi, Hwa Young [Dept. of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); and others

    2015-03-15

    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. 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. 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. 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.

  9. Nephroprotective effect of Corn Silk extract on oxalic acid-induced nephrocalcinosis in rabbit model

    Directory of Open Access Journals (Sweden)

    Faruk Hassan Al-Jawad

    2012-04-01

    Full Text Available ABSTRACT Background : Nephrocalcinosis is a state of deposition of calcium phosphate or oxalate in the renal parenchyma. It may occur in patients with renal tubular acidosis, vitamin D intoxication, and hyperparathyroidism. Corn silk was used in traditional Chinese medicine to relieve renal pains. Aim: To evaluate the effect of Corn silk aqueous extract in reducing calcium deposits from renal parenchyma in oxalic acid-induced nephrocalcinosis model. Materials and methods: Fourteen healthy rabbits were allocated to two groups. Two hours before induction of nephrocalcinosis, one group received water and the other received aqueous extract of corn silk and continued feeding for ten days. Blood samples were collected for biochemical analysis before induction and in the fifth and tenth post-induction day. Urine samples were taken to estimate urinary ca+2 levels and crystals. The histopathological examination was carried to check for crystal deposits in renal tissues. Results: Corn silk aqueous extract produced a significant reduction of blood urea nitrogen(5.2+/-0.08 vs 7.3+/-0.2 mmol/l, serum creatinine (85.9+/-0.2 vs 97.3+/-0.5 mmol/l and serum Na+ levels (137+/-0.2 vs 142.16+/-0.7 mmol/l with non-significant reduction in serum K+ (4.0+/-0.02 vs 4.2+/-0.05. There is a significant reduction in calcium deposition in renal parenchyma in comparison to the control group after ten days of treatment. Conclusion: Corn silk had a significant diuretic effect that accelerates the excretion of urinary calcium. [J Intercult Ethnopharmacol 2012; 1(2.000: 75-78

  10. 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.

    Science.gov (United States)

    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.

  11. Correlation of antispermatozoal antibody with infertility in immunized female rabbits using /sup 14/C-protein A in a filter radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Eng, L.A.; Metz, C.B.

    1986-09-01

    The meaningful detection of antisperm antibody in immunologically infertile females has been confounded by the many methods of assay that exist. With many of these methods there is poor correlation of assay results with infertility. In this report, female rabbits were rendered partially or completely infertile by immunization with sperm fractions. A filter radioassay for antisperm antibody was developed that consists of incubating 10(7) sperm with sperm from immunized rabbits and /sup 14/C-Protein A, a long-lived and versatile indirect radiolabel for many antibodies of the IgG class. The spermatozoa are washed by rapid vacuum filtration on polycarbonate membrane filters instead of by time-consuming centrifugation. The filters with the collected spermatozoa are then counted in a liquid scintillation counter. Sera from female rabbits isoimmunized with sperm antigens show a highly significant correlation (r = -0.904; p less than 0.001) between assay results and infertility as measured by the percentage of eggs that underwent cleavage after artificial insemination.

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

    Energy Technology Data Exchange (ETDEWEB)

    Andino, R.V.; Feldman, D. (Univ. of Alabama, Birmingham (United States))

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Selvakumar Subbian

    2016-02-01

    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.

  15. Rabbit model of intervertebral disc degeneration by external compression device characterized by X-ray, MRI, histology, and cell viability

    Directory of Open Access Journals (Sweden)

    Ismail Ismail

    2006-12-01

    Full Text Available Appropriate experimental animal models, which mimic the degenerative process occurring in human intervertebral disc (IVD breakdown and can be used for new treatment studies such as tissue engineering or disc distraction are lacking. We studied the external compression device that used by Kroeber et al to create intervertebral disc degeneration in rabbit model characterized by X-ray, MRI, Histology, and Cell Viability. Ten NZW rabbit were randomly assigned to one of five groups. Intervertebral disc VL4-L5 are compressed using an external loading device, 1.9 MPa. First group rabbit are loaded for 14 days, second loaded for 28 days, thirth group are loaded for 14 days, and unloaded for 14 days, fourth group loaded for 28 days and unloaded for 28 days. The fifth group, rabbits underwent a sham operation. Additional, rabbits were used as sample for cell viability study. In disc height : sample in group one have biggest decreasing of disc height, that is 23.9 unit. In MRI assessment, the worst grade is grade 3. In histological score, the worst group is group three (58.69, and the best is group 4 (45.69. Group one have the largest dead cell, that are 403.5, and the smallest is group four (124.75. Trypan blue staining showed that group four have better viable cell (91.1 compare than group three (86.4. The study conclude disc degeneration can be created by external axial loading for 14 days in rabbit intervertebral disc. Duration of 28 days unloading gave better result for cells to recover. (Med J Indones 2006; 15:199-207  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: Rabbit model –intervertebral disc degeneration- external compression device-X-ray, MRI, Histology, and Cell viabilty /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso

  16. A new flow-diverter(the FloWise): In vivo evaluation in an elastase-induced rabbit aneurysm model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byung Moon; Kim, Dong Joon; Kim, Dong Ik [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-02-15

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

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

    Science.gov (United States)

    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.

  18. Comprehensive echocardiographic assessment of biventricular function in the rabbit, animal model in cardiovascular research: feasibility and normal values.

    Science.gov (United States)

    Ramos, Sara Roldan; Pieles, Guido; Hui, Wei; Ishii, Ryo; Slorach, Cameron; Friedberg, Mark K

    2017-08-24

    Quantification of cardiac structure and function is central in cardiovascular research. Rabbits are valuable research models of cardiovascular human disease; however, there is little normal data available. The aim of this study was to investigate feasibility and provide normal values for comprehensive echocardiographic assessment of biventricular function in rabbits. New Zealand white rabbits underwent trans-thoracic echocardiography using a general electric (GE) Vivid 7/E9 system with a 10 MHz transducer, under light sedation, to evaluate biventricular function and dimensions. Images for two-dimensional, M-mode, tissue Doppler imaging (TDI) and speckle-tracking strain echocardiography were acquired and analysed. 55 male rabbits (sized matched with a newborn human baby) were studied, mean weight was 2.9 ± 0.23 kg. Adequate images were obtained in 90% for the left ventricle (LV) and 80% for the right ventricle (RV). Two-dimensional speckle-tracking strain was feasible in 60%. Average heart rate was 248 ± 36 beats per minute; LV ejection faction 72 ± 8.0; RV fractional area change 45.9 ± 9.0%; RV myocardial performance index 0.39 ± 0.35; tricuspid annular planar systolic excursion 0.60 ± 0.24 cm. LV TDI parameters were S' 8.6 ± 3.1 cm/s; E' 12.0 ± 4.46 cm/s. RV TDI parameters were S' 10.49 ± 3.18; E' 14.95 ± 4.64 cm/s. LV and RV global peak systolic longitudinal strain were -17 ± 5 and -22 ± 8%, respectively. Comprehensive investigation of biventricular dimensions and function by echocardiography is feasible in the rabbit. Apical views and strain imaging have lower feasibility. Normal values of LV and RV functional parameters are with comparable values to human children. Animal cardiovascular research is key to develop new goals in clinical practice.

  19. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    Directory of Open Access Journals (Sweden)

    Desislava Abadjieva

    Full Text Available Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP 15 and growth differentiation factor (GDF 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR. The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  20. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    Science.gov (United States)

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  1. Transgenic Eimeria magna Pérard, 1925 Displays Similar Parasitological Properties to the Wild-type Strain and Induces an Exogenous Protein-Specific Immune Response in Rabbits (Oryctolagus cuniculus L.)

    Science.gov (United States)

    Tao, Geru; Shi, Tuanyuan; Tang, Xinming; Duszynski, Donald W.; Wang, Yunzhou; Li, Chao; Suo, Jingxia; Tian, Xiuling; Liu, Xianyong; Suo, Xun

    2017-01-01

    Rabbit coccidiosis causes great economic losses to world rabbitries. Little work has been done considering genetic manipulation on the etiological agents, rabbit Eimeria spp. In this study, we constructed a transgenic line of Eimeria magna (EmagER) expressing enhanced yellow fluorescent protein (EYFP) and red fluorescent protein (RFP) using regulatory sequences of Eimeria tenella and Toxoplasma gondii. We observed the life cycle of EmagER and confirmed that the transgenic parasites express exogenous proteins targeted to different cellular compartments throughout the entire life cycle. EYFP was expressed mainly in the nucleus and RFP both in the nucleus and cytoplasm. Then, coccidia-free, laboratory-reared 40-day-old rabbits were primarily infected with either EmagER or wild-type strain oocysts and challenged with the wild-type strain. EmagER showed similar reproductivity and immunogenicity to the wild-type strain. Finally, we examined the foreign protein-specific immune response elicited by EmagER. Rabbits were immunized with either transgenic or wild-type oocysts. Immune response against parasite-soluble antigen, EYFP and RFP in spleen, and mesenteric lymph nodes were detected by quantitative real-time PCR. The relative expression level of IFN-γ, IL-2, and TNF-α were higher in EmagER-immunized rabbits than wild-type parasites-immunized rabbits after stimulation with EYFP and RFP. Our study confirmed that a specific immune response was induced by the exogenous protein expressed by EmagER and favored future studies on application of transgenic rabbit coccidia as recombinant vaccine vectors. PMID:28167939

  2. Transgenic Eimeria magna Pérard, 1925 Displays Similar Parasitological Properties to the Wild-type Strain and Induces an Exogenous Protein-Specific Immune Response in Rabbits (Oryctolagus cuniculus L.).

    Science.gov (United States)

    Tao, Geru; Shi, Tuanyuan; Tang, Xinming; Duszynski, Donald W; Wang, Yunzhou; Li, Chao; Suo, Jingxia; Tian, Xiuling; Liu, Xianyong; Suo, Xun

    2017-01-01

    Rabbit coccidiosis causes great economic losses to world rabbitries. Little work has been done considering genetic manipulation on the etiological agents, rabbit Eimeria spp. In this study, we constructed a transgenic line of Eimeria magna (EmagER) expressing enhanced yellow fluorescent protein (EYFP) and red fluorescent protein (RFP) using regulatory sequences of Eimeria tenella and Toxoplasma gondii. We observed the life cycle of EmagER and confirmed that the transgenic parasites express exogenous proteins targeted to different cellular compartments throughout the entire life cycle. EYFP was expressed mainly in the nucleus and RFP both in the nucleus and cytoplasm. Then, coccidia-free, laboratory-reared 40-day-old rabbits were primarily infected with either EmagER or wild-type strain oocysts and challenged with the wild-type strain. EmagER showed similar reproductivity and immunogenicity to the wild-type strain. Finally, we examined the foreign protein-specific immune response elicited by EmagER. Rabbits were immunized with either transgenic or wild-type oocysts. Immune response against parasite-soluble antigen, EYFP and RFP in spleen, and mesenteric lymph nodes were detected by quantitative real-time PCR. The relative expression level of IFN-γ, IL-2, and TNF-α were higher in EmagER-immunized rabbits than wild-type parasites-immunized rabbits after stimulation with EYFP and RFP. Our study confirmed that a specific immune response was induced by the exogenous protein expressed by EmagER and favored future studies on application of transgenic rabbit coccidia as recombinant vaccine vectors.

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

    Science.gov (United States)

    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

  4. Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride.

    Directory of Open Access Journals (Sweden)

    Chaoyang Li

    Full Text Available 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.

  5. Development of a novel rabbit model of abdominal aortic aneurysm via a combination of periaortic calcium chloride and elastase incubation.

    Directory of Open Access Journals (Sweden)

    Yonghua Bi

    Full Text Available 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.

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

    Science.gov (United States)

    Cooke, Daniel L; 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

    2015-02-01

    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

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

    Science.gov (United States)

    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

  8. Effects of chronic heat stress on the expressions of heat shock proteins 60, 70, 90, A2, and HSC70 in the rabbit testis.

    Science.gov (United States)

    Pei, Yangli; Wu, Yingjie; Qin, Yinghe

    2012-01-01

    Few studies have focused on the expression of heat shock proteins (HSPs) after chronic heat stress. The objective of this study was to investigate the effect of chronic high temperature-humidity index treatment on the expressions of HSP60, HSP70, HSP90, HSPA2 and HSC70, in the Rex rabbit testis and the expressions of these proteins after recovery from the chronic heat shock. Thirty mature male rabbits of the same age were randomly divided into three groups: control, heat stress, and recovery. The western blot results showed that the expressional levels of HSP60, HSP90, and HSC70 increased significantly and HSPA2 was elevated slightly after a 9-week heat treatment. HSP70 was absent in the control testis and had a high level of expression after heat stress. All of these proteins partially reverted back to normal levels after a 9-week recovery. The immunohistochemical results indicated that the expression patterns of HSP60, HSP90, HSPA2, and HSC70 did not change.

  9. Application of Response Surface Methodology to Study the Effects of Brisket Fat, Soy Protein Isolate, and Cornstarch on Nutritional and Textural Properties of Rabbit Sausages

    Directory of Open Access Journals (Sweden)

    Joseph M. Wambui

    2017-01-01

    Full Text Available The effects of brisket fat, soy protein isolate, and cornstarch on chemical and textural properties of rabbit sausages were studied using surface response methodology. Sausage samples were prepared using a five-level three-variable Central Composite Rotatable Design with 16 combinations, including two replicates of the center point, carried out in random order. The level of brisket fat (BF, soy protein isolate (SPI, and cornstarch (CS in the sausage formulation ranged within 8.3–16.7%, 0.7–2.3%, and 1.3–4.7%, respectively. Increasing BF decreased moisture and ash contents but increased protein and fat contents of the sausages (p<0.05. Increasing SPI increased moisture content but decreased ash and carbohydrate contents of the sausages (p<0.05. Increasing CS increased carbohydrate content (p<0.05. Increasing BF increased hardness, adhesiveness, cohesiveness, and chewiness but decreased springiness (p<0.05. SPI addition increased springiness but decreased adhesiveness, cohesiveness, and chewiness (p<0.05. In conclusion, varying the levels of BF and SPI had a more significant effect on chemical and textural properties of rabbit sausages than CS.

  10. Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Cao Wei [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: zjfurong2008@126.com; Wan Yi [Department of Health Statistics, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Liang Zhihui [Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province 050082 (China); Duan Yunyou; Liu Xi [Department of Ultrasonography, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinshi Road, Xi' an 710038 (China); Wang Zhimin; Liu Yiyong; Zhu Jia; Liu Xiongtao [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China); Zhang Hongxin [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: cawe-001@163.com

    2010-02-15

    Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. Results: The tumor growth rate in the lipiodol (60 deg. C) group (0.92 {+-} 0.21, tumor volume from 1811 {+-} 435 to 1670 {+-} 564 mm{sup 3}) was significantly lower than that in the control group (3.48 {+-} 1.17, tumor volume from 1808 {+-} 756 to 5747 {+-} 1341 mm{sup 3}) (P < 0.05) and in the doxorubicin-lipiodol (37 deg. C) group (1.69 {+-} 0.26, tumor volume from 1881 {+-} 641 to 2428 {+-} 752 mm{sup 3}) (P < 0.05). Consequently, the survival period of the animals in the lipiodol (60 deg. C) group (41.0 {+-} 3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 deg. C) group (38.0 {+-} 2.5 days) (P < 0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 deg. C) group (148.2 {+-} 11

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2014-01-01

    Full Text Available The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+ transient, and iNa changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase in iNa and iCa,T which were reduced by the mutation.

  14. Isoprenaline: a potential contributor in sick sinus syndrome--insights from a mathematical model of the rabbit sinoatrial node.

    Science.gov (United States)

    Li, Xiang; Zhang, Ji-qian; Shuai, Jian-wei

    2014-01-01

    The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca²⁺ transient, and i(Na) changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase in i(Na) and i(Ca,T) which were reduced by the mutation.

  15. Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

    Science.gov (United States)

    Ricci, Francesca; Catozzi, Chiara; Murgia, Xabier; Rosa, Brenda; Amidani, Davide; Lorenzini, Luca; Bianco, Federico; Rivetti, Claudio; Catinella, Silvia; Villetti, Gino; Civelli, Maurizio; Pioselli, Barbara; Dani, Carlo; Salomone, Fabrizio

    2017-01-01

    Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant. PMID:28060859

  16. Application of layered poly (L-lactic acid cell free scaffold in a rabbit rotator cuff defect model

    Directory of Open Access Journals (Sweden)

    Inui Atsuyuki

    2011-12-01

    Full Text Available Abstract Background This study evaluated the application of a layered cell free poly (L-lactic acid (PLLA scaffold to regenerate an infraspinatus tendon defect in a rabbit model. We hypothesized that PLLA scaffold without cultivated cells would lead to regeneration of tissue with mechanical properties similar to reattached infraspinatus without tendon defects. Methods Layered PLLA fabric with a smooth surface on one side and a pile-finished surface on the other side was used. Novel form of layered PLLA scaffold was created by superimposing 2 PLLA fabrics. Defects of the infraspinatus tendon were created in 32 rabbits and the PLLA scaffolds were transplanted, four rabbits were used as normal control. Contralateral infraspinatus tendons were reattached to humeral head without scaffold implantation. Histological and mechanical evaluations were performed at 4, 8, and 16 weeks after operation. Results At 4 weeks postoperatively, cell migration was observed in the interstice of the PLLA fibers. Regenerated tissue was directly connected to the bone composed mainly of type III collagen, at 16 weeks postoperatively. The ultimate failure load increased in a time-dependent manner and no statistical difference was seen between normal infraspinatus tendon and scaffold group at 8 and 16 weeks postoperatively. There were no differences between scaffold group and reattach group at each time of point. The stiffness did not improve significantly in both groups. Conclusions A novel form of layered PLLA scaffold has the potential to induce cell migration into the scaffold and to bridge the tendon defect with mechanical properties similar to reattached infraspinatus tendon model.

  17. The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model.

    Science.gov (United States)

    Szkutnik-Fiedler, Danuta; Grabowski, Tomasz; Balcerkiewicz, Monika; Michalak, Michał; Pilipczuk, Irina; Wyrowski, Łukasz; Urjasz, Hanna; Grześkowiak, Edmund

    2017-06-01

    The combined use of tramadol with selective serotonin and norepinephrine reuptake inhibitors e.g. venlafaxine may be associated with serotonin syndrome. No previous studies exist examining the influence of a weak CYP2D6 inhibitor venlafaxine on the pharmacokinetics of tramadol. Therefore, the aim of this study was to determine the effect of a single and chronic administration of venlafaxine on the pharmacokinetics of tramadol using a rabbit model. Adult New Zealand white rabbits of both sexes (n=21) were used. Animals received 100mg of tramadol per os (one slow release tablet) and 75mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1day group - a single dose of tramadol and venlafaxine, 7 and 14days groups - seven and fourteen days administration of venlafaxine once daily plus a single dose of tramadol on the last day of the study. Venlafaxine administration over a period of 7 and 14days resulted in faster elimination of tramadol compared to the control group: significantly higher values of k el, and lower values of t1/2kel and MRT for the 7 and 14days group were observed. Although no differences in bioavailability of tramadol were obtained. Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Application of rabbits in biomedical research: a review.

    OpenAIRE

    Bosze, Zs.; Houdebine, L M

    2006-01-01

    The first transgenic rabbits were obtained two decades ago by pronuclear microinjection. Several characteristics of rabbit made it the first and classical model for the study of lipoproteins and atherosclerosis. Rabbit models include normal cholesterol-fed rabbits, spontaneous mutants for lipid metabolism and transgenic rabbits. Though most molecular investigations of the cardiovascular system have used transgenic mice, the small rodents do not accurately reflect crucial facets of human cardi...

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

    Science.gov (United States)

    2008-05-01

    developed by Schultz et al. (15) utilized a vacuum trephine apparatus attached to the center of the cornea, through which a toxic agent could be...for the minor procedures of tattooing , nail clipping, and a screening ophthalmologic exam for any preexisting lesions and/or other abnormalities...Rabbits were tattooed using an AIMS machine (Animal Identification and Marking Systems; AIMS, Budd Lake, NJ) for placing permanent identification numbers

  20. Retinal endoilluminator toxicity of xenon and light-emitting diode (LED) light source: rabbit model.

    Science.gov (United States)

    Aydin, Bahri; Dinç, Erdem; Yilmaz, S Necat; Altiparmak, U Emrah; Yülek, Fatma; Ertekin, Sevda; Yilmaz, Mustafa; Yakın, Mehmet

    2014-09-01

    This study evaluates retinal toxicity due to endoillumination with the light-emitting diode (LED) light source in comparison to endoillumination with xenon light source. Twenty-five eyes of 14 New Zealand pigmented rabbits were used in the study. The LED light (Omesis Medical Systems, Turkey) group was composed of 7 right eyes, while the other 7 right eyes constituted the xenon group (420 nm filter, 357mW/cm(2)) (Bright Star; DORC, Zuidland, Netherlands). Eleven untreated left eyes composed the control group. Twenty gauge pars plana incision 1.5 mm behind the limbus was performed in the right eyes. Twenty gauge bullet type fiberoptic endoilluminator was inserted into the eye from the incision without any pars plana vitrectomy. Fiberoptic endoilluminator was placed in such a way that it was directed toward visual streak of the rabbit retina with a 5 mm distance to retinal surface. Endoillumination was then applied for 20 min with a maximum light intensity for LED and xenon light. In left control eyes, no surgical procedure and no endoillumination were performed. One week after the endoillumination procedure, both eyes of the rabbits were enucleated following electroretinography. Sections stained with hematoxylin and eosin to evaluate morphologic changes. Retina tissues were assessed by active caspase-3 staining. There was no difference in the shape of the waveforms recorded in the eyes endoilluminated with LED light and xenon light sources compared to control eyes both before and after endoillumination application (p > 0.05). Microscopic evaluation of the retinas with hematoxylin and eosin staining demonstrated that all study groups have normal histologic properties similar to control group. No apoptosis positive cells were found within all sections in all groups. When the LED light source is used with maximum power and limited duration for endoillumination in rabbit eyes it does not produce phototoxic effects that may be detectable by electrophysiology

  1. Human amniotic membrane as an intestinal patch for neomucosal growth in the rabbit model.

    Science.gov (United States)

    Barlas, M; Gökçora, H; Erekul, S; Dindar, H; Yücesan, S

    1992-05-01

    This experiment was carried out as a preliminary study, an attempt to grow new intestinal mucosa on human amniotic membrane in the terminal ileum in 37 rabbits. After ketamin sulfate anesthesia at laparatomy, 5-cm ileal defects were patched with human amniotic membrane (5 x 2 cm). These patched intestines were investigated on the first postoperative day and the 2nd, 5th, 10th, and 20th weeks corresponding to 4, 5, 5, 10, and 10 rabbits, respectively. Only three rabbits died in the early postoperative period. There was no evidence of intestinal obstruction or dilatation with barium meal. Microscopically, the neomucosa consisted of a thin layer of columnar epithelial cells at 2 weeks with more maturity of the villi and less irregularity and branching by 20 weeks. All patches were covered with neomucosa commencing at 2 weeks and covering the whole patch area by 20 weeks. This technique's advantages are the large size and the ease of the availability of the human amniotic membrane for neonates at risk without jeopardizing the neonates tissues. It is hoped that this method might be considered when neonatal material is scarce.

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

    Science.gov (United States)

    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.

  3. Hair analysis used to assess chronic exposure to the organophosphate diazinon: a model study with rabbits.

    Science.gov (United States)

    Tutudaki, Maria; Tsakalof, Andreas K; Tsatsakis, Aristidis M

    2003-03-01

    The main purpose of the present study was to determine whether hair analysis would be a suitable method to assess chronic exposure of rabbits to the pesticide diazinon. A controlled study was designed, in which white rabbits of the New Zealand variety were systemically exposed to two dosage levels (15 mg/kg per day and 8 mg/kg per day) of the pesticide, through their drinking water, for a period of 4 months. Hair samples from the back of the rabbits were removed before commencing the experiment and at the end of the dosing period. Parallel experiments with spiked hair were carried out in order to design a simple and efficient method of extraction of diazinon from hair. The hair was pulverized in a ball mill homogenizer, incubated in methanol at 37 degrees C overnight, liquid-liquid extracted with ethyl acetate and measured by chromatography techniques (GC-NPD and GC-MS) for confirmation. The concentration of the diazinon in the hair of the exposed animals ranged from 0.11 to 0.26 ng/mg hair. It was concluded that there is a relationship between the administered dose and the detected pesticide concentration in hair. Finally, it seems that hair analysis may be used to investigate chronic exposure to the pesticide.

  4. RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are infectious in rabbits.

    Science.gov (United States)

    Cossaboom, Caitlin M; Huang, Yao-Wei; Yugo, Danielle M; Kenney, Scott P; Piñeyro, Pablo; Matzinger, Shannon R; Heffron, C Lynn; Pierson, F William; Meng, Xiang-Jin

    2014-11-07

    Hepatitis E virus (HEV), the causative agent of hepatitis E, is a single-stranded positive-sense RNA virus belonging to the family Hepeviridae. At least four genotypes of the family infect humans: genotypes 1 and 2 are transmitted to humans through contaminated water, while genotypes 3 and 4 are zoonotic and have animal reservoirs. A novel strain of HEV recently identified in rabbits is a distant member of genotype 3, and thus poses a potential risk of zoonotic transmission to humans. The objective of this study was to construct and characterize an infectious cDNA clone of the rabbit HEV. Two full-length cDNA clones of rabbit HEV, pT7g-rabHEV and pT7-rabHEV, were constructed and their infectivity was tested by in vitro transfection of Huh7 human liver cells and by direct intrahepatic inoculation of rabbits with capped RNA transcripts. Results showed that positive signal for rabbit HEV protein was detected by an immunofluorescence assay with a HEV-specific antibody in Huh7 human liver cells transfected with capped RNA transcripts from the two full-length cDNA clones. Rabbits intrahepatically inoculated with capped RNA transcripts from each of the two clones developed active HEV infection as evidenced by seroconversion to anti-HEV antibodies, and detection of rabbit HEV RNA in sera and feces of inoculated animals. The availability of a rabbit HEV infectious cDNA clone now affords us the ability to delineate the mechanism of HEV replication and cross-species infection in a small animal model.

  5. The preparation of aseptic rabbit tissue cage infection model%兔组织笼无菌感染模型的制备

    Institute of Scientific and Technical Information of China (English)

    刘树玲; 丁丽; 邢昆

    2015-01-01

    目的:制备兔组织笼无菌感染模型,为药物药动学-药效学结合模型(pharmacokinetic‐pharmaco‐dynamic modeling ,PK‐PD)研究提供在体动物实验载体。方法选取健康家兔28只,耳缘静脉注射盐酸赛拉嗪注射液0.15ml/kg麻醉,每只分别背部备皮、切开皮肤,然后在皮下植入长约5cm的无菌中空胸腔引流管1个,继而在无菌操作下手术缝合。术后应用青霉素肌肉注射3d以预防感染。结果5只家兔先后因不同原因死亡,23只家兔均获得清亮的无菌组织液,成功建立兔组织模型,成功率为82.14%。结论通过严格控制无菌操作,选择合适的麻醉剂,手术刀口选择在兔背部,术后及时预防感染,可以成功制备兔组织笼无菌感染模型,并获得清亮的无菌组织液。%Objective To prepare a rabbit tissue cage model so as to provide drug animal carrier in vivo for drug PK‐PD modeling study .Methods 28 healthy rabbits were selected and injected with the anesthesia xylazine iv respectively .The back hair was cut in each rabbit ,and then the skin was cut open .A 5cm of sterile hollow chest tube drainage was implanted subcutaneously .In the end the wound was sewed up with aseptic technique .After op‐eration penicillin im was injected for 3 days to prevent infection .Results Among the 28 rabbits ,5 rabbits were dead due to different causes .Clear and sterile tissue fluid were gotten from other 23 rabbits .A rabbit tissue model was established successfully ,and the success rate was 82 .14% .Conclusion By stricted controlling aseptic opera‐tion ,selecting the appropriate anesthesia and surgical incision in the back of the rabbit ,timely postoperative anti‐infection ,a rabbit tissue cage model can be successfully established ,so does clear tissue fluid .

  6. Rabbit and human hepatitis E virus strains belong to a single serotype.

    Science.gov (United States)

    Wang, Song; Cheng, Xianfeng; Dai, Xing; Dong, Chen; Xu, Mingjie; Liang, Jiuhong; Dong, Min; Purdy, Michael A; Meng, Jihong

    2013-09-01

    Hepatitis E virus (HEV) is a zoonotic pathogen and all four established genotypes of HEV belong to a single serotype. The recently identified rabbit HEV is antigenically and genetically related to human HEV. It is unclear whether rabbit HEV belongs to the same serotype as human HEV. The purpose of this study was to determine the serotypic relationship between rabbit and human HEVs. HEV ORF2 recombinant capsid protein p166 (amino acids 452-617) of four known HEV genotypes and rabbit HEV were used to induce immune serum, which were evaluated for their ability to neutralize human HEV genotype 1, 4, and rabbit HEV strains by an in vitro PCR-based HEV neutralization assay. Immune sera of five kinds of p166 proteins were all found to neutralize or cross-neutralize the three different HEV strains, suggesting a common neutralization epitope(s) existing between human and rabbit HEV. Rabbit models of a second-passage rabbit HEV strain, JS204-2, and a genotype 4 human HEV strain, NJ703, were established as evidenced by fecal virus shedding, viremia and anti-HEV IgG seroconversion. Six rabbits, recovered from JS204 infection, were challenged with NJ703, and another six recovered from NJ703 infection were challenged with JS204-2. After challenge, viremia was not detected, shorter fecal virus shedding durations and obvious early stage declines in anti-HEV IgG values were observed. The results from this study indicate that rabbit HEV belongs to the same serotype as human HEV.

  7. Comparative study between original and traditional method in establishing a chronic sinus node damage model in rabbit.

    Science.gov (United States)

    Liu, Ru-xiu; Wang, Yan-li; Li, Hui-bo; Wang, Ni-na; Bao, Mei-jing; Xu, Li-ya

    2012-12-01

    Sick Sinus Syndrome is a common and refractory arrhythmia, needing further study in which setting up a credible sinus node damage model is important. To explore the feasibility and superiority of an original formaldehyde pinpoint pressing permeation (FPPP) method for building a chronic sinus node damage (CSND) model, 5 rabbits were chosen from 35 as a sham-operation group, and the remaining were randomly divided into two groups: the formaldehyde wet compressing (FWC) group, in which models were established by applying a cotton bud dipped in 20% formaldehyde onto the sinus node (SN) area, and the FPPP group, in which models were established by injecting formaldehyde into the SN area through a self-made pinpointing and injecting electrode. We found that in both groups, the HR at 2 h, 24 h, 1 wk, and 2 wk after modeling decreased compared with premodeling; sinoatrial conduction time, sinus node recovery time, and corrected sinus node recovery time were prolonged compared with premodeling. The indexes mentioned shortened by 2 wk after modeling compared with 2 h in the FWC group, whereas they were stable after modeling in the FPPP group. The modeling achievement ratio in the FPPP group was higher and the death rate was lower. Under light microscope, paraffin sections of the SN tissue and cells showed severe injury in both groups. The results indicate that the CSND models in rabbits can be successfully established by the FPPP method, with higher achievement ratio, lower death rate, better stabilization effect, and less damaging comparing with the traditional method.

  8. Computational modeling of membrane proteins.

    Science.gov (United States)

    Koehler Leman, Julia; Ulmschneider, Martin B; Gray, Jeffrey J

    2015-01-01

    The determination of membrane protein (MP) structures has always trailed that of soluble proteins due to difficulties in their overexpression, reconstitution into membrane mimetics, and subsequent structure determination. The percentage of MP structures in the protein databank (PDB) has been at a constant 1-2% for the last decade. In contrast, over half of all drugs target MPs, only highlighting how little we understand about drug-specific effects in the human body. To reduce this gap, researchers have attempted to predict structural features of MPs even before the first structure was experimentally elucidated. In this review, we present current computational methods to predict MP structure, starting with secondary structure prediction, prediction of trans-membrane spans, and topology. Even though these methods generate reliable predictions, challenges such as predicting kinks or precise beginnings and ends of secondary structure elements are still waiting to be addressed. We describe recent developments in the prediction of 3D structures of both α-helical MPs as well as β-barrels using comparative modeling techniques, de novo methods, and molecular dynamics (MD) simulations. The increase of MP structures has (1) facilitated comparative modeling due to availability of more and better templates, and (2) improved the statistics for knowledge-based scoring functions. Moreover, de novo methods have benefited from the use of correlated mutations as restraints. Finally, we outline current advances that will likely shape the field in the forthcoming decade.

  9. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

    Directory of Open Access Journals (Sweden)

    Rui V Simões

    Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  10. Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Nasui, Otilia C.; Chan, Michael W.; Nathanael, George; Rayner, Tammy; Weiss, Ruth; Detzler, Garry; Zhong, Anguo [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto, ON (Canada); Miller, Elka [Children' s Hospital of Eastern Ontario (CHEO), Department of Diagnostic Imaging, Ottawa, ON (Canada); Belik, Jaques [The Hospital for Sick Children, Department of Neonatology, Toronto, ON (Canada); Cheng, Hai-Ling; Kassner, Andrea; Doria, Andrea S. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Moineddin, Rahim [Department of Public Health, Family and Community Medicine, Toronto, ON (Canada); Jong, Roland; Rogers, Marianne [Mount Sinai Hospital, Department of Pathology, Toronto, ON (Canada)

    2014-11-15

    Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO{sub 2}) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. (orig.)

  11. Effect of Straight-leg-raising Movement on Epidural Fibrosis in Early Stage after Laminectomy in a Rabbit Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To determine the effect of straight-leg-raising (SLR) movement on epidural fibrosis after laminectomy, 40 adult New Zealand rabbits were selected as laminectomy models in the study. They were divided into 2 groups: a SLR group (group S) and a control group (group C) randomly, with each group having 20 animals. All rabbits were subjected to total laminectomy in the site of S1. Every 5 rabbits in each group selected randomly were killed at the 1st, 2nd, 4th, and 8th week after the surgery. Segments of spines from L7 to S2 were removed en bloc. After gross evaluation, specimens were sliced up. The slices were stained by HE and Masson's trichrome methods respectively for histological examination. Our results showed that formation process of scar in group S was retarded as compared with that of group C at the time of the 2nd-week, but there was no statistical difference between groups in the adhesion degree (P≥0.05). At the 4th and 8th week, the epidural fibrosis of group S was more serious than that of group C. Since the 2nd-week, the area of scar in group S was larger than that of group C. The number of fibroblasts and inflammatory cells in group S were larger than those of group C at early stage. But in later stage, there was no statistical significance between the two groups. It is concluded that SLR movement after laminectomy may promote the formation of epidural fibrosis and retard the maturity of scar. SLR movement can also aggravate scar adhesion.

  12. Rotator cuff repair using a decellularized tendon slices graft: an in vivo study in a rabbit model.

    Science.gov (United States)

    Pan, Juan; Liu, Guo-Ming; Ning, Liang-Ju; Zhang, Yi; Luo, Jing-Cong; Huang, Fu-Guo; Qin, Ting-Wu

    2015-05-01

    Although varieties of surgical repair techniques and materials have been used to repair rotator cuff defects, re-tearing frequently occurs. The purpose of this study is to evaluate the postoperative outcomes of rotator cuff repairs with a decellularized tendon slices (DTSs) graft in a rabbit model. Large defects in the infraspinatus tendons were created bilaterally in 21 rabbits. The graft group underwent reconstruction of the defects with the DTSs grafts, while the defect group did not undergo any treatment. The specimens underwent histological observation, biomechanical testing, and magnetic resonance imaging (MRI) detection at 4, 8, and 12 weeks after surgery. In addition, 2 rabbits that were not operated on were used for MRI detection as a normal reference. Histological analysis revealed that the graft promoted host cell ingrowth and tissue integration, and a tendon-like structure developed at 12 weeks. The ultimate tensile load had a significant difference between specimens at 4 and 12 weeks in the graft group, but there was no significant difference between the graft group and the defect group. In the graft group, the stiffness at 12 weeks was significantly greater than that at 4 or 8 weeks, and it was also greater than the stiffness in the defect group at 12 weeks. MRI demonstrated that the signal strength of the regenerative tissue from the graft group at 12 weeks was similar to that of normal infraspinatus tendon. The DTSs graft allowed for incorporation of host tendon and improved the biomechanical performance of the regenerative tendon. Therefore, the graft could be a promising bioscaffold to enhance the surgical repair of large rotator cuff defects and consequently improve the clinical outcome of rotator cuff tears.

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

    Science.gov (United States)

    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.

  14. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    Science.gov (United States)

    Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

    2014-02-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

  15. Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

    Directory of Open Access Journals (Sweden)

    Homšek Irena

    2011-01-01

    Full Text Available Controlled-release (CR pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

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

    Science.gov (United States)

    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.

  17. Effect of the Multiglycoside of Tripterygium Wilfordii Hookf.(Tii)on Cornea Allograft Rejection Model in Rabbit

    Institute of Scientific and Technical Information of China (English)

    ZhijieLi; ChenLi

    1995-01-01

    Purpose:Toexamine the effect of Tii treatment of cornea graft survival in a rab-bit model.Methods:Tii was administrated orally after eccentrical corneal transplantation.Survival times were determined by biomicroscopy.Cytotoxic T lymphocytes(CTL)and delayed-type hypersensitivity(DTH)responses to donor alloantigens were assessed at ady 16after heterotopic corneal grafts.Results:Administration of Tii reduced the incidence and prologed the graft sur-vival time.Both CTLand DTH responses to donor alloantigens were severely ed-pressed in hosts treated with Tii.However,combination of Tii and cyclosporine further enhanced the immunosuppressive effects described above.Conclusions:Tii is a potent immunosuppressant with the ability to prolong allo-graft survival in the rabbit penetrating keratoplasty model and may have coordi-native effects with CsA through different mechanisms.Further studies are neces-sary to define any potentially coordinative role in the prevention of allograft rejec-tion in human keratoplasty.Eye Science 1995;11:168-172.

  18. Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model.

    Science.gov (United States)

    Back, Ja Hoon; Cho, Wan Jin; Kim, Jun Ho; Park, Il Kyu; Kwon, Sung Won

    2016-04-01

    Postsurgical adhesion formation is a concern in every field of surgery. We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation in a standardized rabbit model. To evaluate the anti-adhesion effect, a uterus-abdominal wall abrasion model was created in rabbits. On the surface of the injured uterus, an anti-adhesive agent, Interceed(®) or MP, was applied (positive control and study groups, respectively; n = 10 each). In another group of 10 animals, neither agent was applied (negative control group). The adhesion levels were graded 3 weeks after surgery. Acute and chronic toxicity was also evaluated. The grade of adhesion was significantly lower in the MP group than in the negative control and positive control groups. No evidence of acute or chronic toxicity induced by this material was found in blood and tissue analysis. MP shows potential as an effective novel type of resorbable biomaterial to reduce postoperative adhesion. The easy placement and handling of this material make the MP powder attractive as a tissue adhesion barrier.

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

    Science.gov (United States)

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

    2014-08-01

    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.

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

    Science.gov (United States)

    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.

  1. In Vitro Dissolution and In Vivo Bioavailability of Six Brands of Ciprofloxacin Tablets Administered in Rabbits and Their Pharmacokinetic Modeling

    Directory of Open Access Journals (Sweden)

    Sahar Fahmy

    2014-01-01

    Full Text Available This study was undertaken to assess the in vitro dissolution and in vivo bioavailability of six brands of ciprofloxacin oral tablets available in the UAE market using rabbits. The in vitro dissolution profiles of the six ciprofloxacin products were determined using the USP dissolution paddle method. Pharmacokinetic modeling using compartmental and noncompartmental analysis was done to determine the pharmacokinetic parameters of ciprofloxacin after single-dose oral administration. In vitro release study revealed that the amount of ciprofloxacin released in 20 minutes was not less than 80% of the labeled amount which is in accordance with the pharmacopoeial requirements. All tested products are considered to be very rapid dissolving except for formulae A and D. Ciprofloxacin plasma concentration in rabbits was best fitted to a two-compartment open model. The lowest bioavailability was determined to be for product A (93.24% while the highest bioavailability was determined to be for product E (108.01%. Postmarketing surveillance is very crucial to ensure product quality and eliminating substandard products to be distributed and, consequently, ensure better patient clinical outcome. The tested ciprofloxacin generic products distributed in the UAE market were proven to be of good quality and could be used interchangeably with the branded ciprofloxacin product.

  2. Effects of MBL-associated serine protease-2 (MASP-2) on liquefaction and ulceration in rabbit skin model of tuberculosis.

    Science.gov (United States)

    Dong, Xinfang; Luo, Yanping; Gao, Qi; Lu, Xiaoling; Wang, Qian; Zhang, Yuan; Liu, Xun; Zhang, Lifeng; Wang, Jingqiu; Ma, Xingming; Zhu, Bingdong

    2016-10-01

    Tuberculosis is a chronic infectious disease, which caused by Mycobacterium tuberculosis. It typically affects the functions of the lung and causes high morbidity and mortality rates worldwide. The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. However, what is the specific effection between tuberculosis and complement is unknown. Mannose-binding lectin (MBL), a recognition subunit, binds to arrays of carbohydrates on the surfaces of pathogens, which results in the activation of MBL-associated serine protease-2 to trigger a downstream reaction cascade of complement system. The effects of human MBL-associated serine protease-2 (hMASP-2) were assessed in a rabbit-skin model by intradermal injection of 5 × 10(6) viable BCG bacilli. The rAd-hMASP-2 accelerated the formation of liquefaction and healing of the granuloma lesions, reduced the bacteria loads of the skin nodules. The serum levels of IL-2 and IFN-γ were significantly increasing during the granuloma and liquefaction phases in the rAd-hMASP-2 group. This study suggests that hMASP-2 can induce a protective efficacy in BCG-infected rabbit skin models, which affects both the progress of lesions and the survival of the mycobacteria within them. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; En-Hua Xiao; Jian-Bin Liu; Zhong He; Ke Jin; Cong Ma; Jun Xiang; Jian-Hua Xiao; Wei-Jian Chen

    2008-01-01

    AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC)on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and StTept Avidin-Biotin Complex (SABC)immunohistochemi