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Sample records for promising canine model

  1. Laparoscopic radical prostatectomy in the canine model.

    Science.gov (United States)

    Price, D T; Chari, R S; Neighbors, J D; Eubanks, S; Schuessler, W W; Preminger, G M

    1996-12-01

    The purpose of this study was to determine the feasibility of performing laparoscopic radical prostatectomy in a canine model. Laparoscopic radical prostatectomy was performed on six adult male canines. A new endoscopic needle driver was used to construct a secure vesicourethral anastomosis. Average operative time required to complete the procedure was 304 min (range 270-345 min). Dissection of the prostate gland took an average of 67 min (range 35-90 min), and construction of the vesicourethral anastomosis took 154 min (rage 80-240 min). There were no intraoperative complications and only one postoperative complication (anastomotic leak). Five of the six animals recovered uneventfully from the procedure, and their foley catheters were removed 10-14 days postoperatively after a retrograde cystourethrogram demonstrated an intact vesicourethral anastomosis. Four (80%) of the surviving animals were clinically continent within 10 days after catheter removal. Post mortem examination confirmed that the vesicourethral anastomosis was intact with no evidence of urine extravasation. These data demonstrate the feasibility of laparoscopic radical prostatectomy in a canine model, and suggest that additional work with this technique should be continued to develop its potential clinical application.

  2. Embolus radiolabelling in a new canine model

    International Nuclear Information System (INIS)

    Kaufman, H.H.; Huchton, J.D.; Woo, J.; Cannon, D.C.; Anderson, J.H.

    1980-01-01

    Embolus radiolabelling with 131 I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm 3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli. (author)

  3. Models of experimental saccular aneurysms of carotid arteries in canine

    International Nuclear Information System (INIS)

    Zhang Haixia; Cheng Yingsheng; Li Minghua

    2006-01-01

    Objective: To study the availability by making experimental saccular aneurysm models of carotid arteries in canine similar to human intracranial aneurysms. Methods: Twenty healthy canines with experimental saccular side-wall aneurysms of carotid arteries were created successfully by surgery. Results: Forty experimental saccular side-wall aneurysms of carotid arteries were created successfully with 36 aneurysms and parent arteries maintaining patency with each other and four spontaneously occluded confirmed by angiography. Model successful rate reached 90%. Conclusions: Experimental saccular side-wall aneurysms of carotid arteries in canines were one of best models created for simulating human intracranial aneurysms. (authors)

  4. Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Siemann, Dietmar W; Abbott, Jeffrey R; Kiupel, Matti; Salute, Marc E; Milner, Rowan J

    2014-03-01

    Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (Posteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.

  5. Towards immunotherapy with redirected T cells in a large animal model: Ex vivo activation, expansion, and genetic modification of canine T cells

    Science.gov (United States)

    Mata, Melinda; Vera, Juan; Gerken, Claudia; Rooney, Cliona M.; Miller, Tasha; Pfent, Catherine; Wang, Lisa L.; Wilson-Robles, Heather M.; Gottschalk, Stephen

    2014-01-01

    Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown promising anti-tumor activity in early phase clinical studies, especially for hematological malignancies. However, most preclinical models do not reliably mimic human disease. We reasoned that developing an adoptive T-cell therapy approach for spontaneous osteosarcoma (OS) occurring in dogs would more closely reproduce the condition in human cancer. To generate CAR-expressing canine T cells we developed expansion and transduction protocols that allow for the generation of sufficient numbers of CAR-expressing canine T cells for future clinical studies in dogs within 2 weeks of ex vivo culture. To evaluate the functionality of CAR-expressing canine T cells we targeted HER2-positive OS. We demonstrate that canine OS is positive for HER2, and that canine T cells expressing a HER2-specific CAR with human-derived transmembrane and CD28.ζ signaling domains recognize and kill HER2-positive canine OS cell lines in an antigen-dependent manner. To reduce the potential immunogenicity of the CAR we evaluated a CAR with canine-derived transmembrane and signaling domains, and found no functional difference between human and canine CARs. Hence, we have successfully developed a strategy to generate CAR-expressing canine T cells for future preclinical studies in dogs. Testing T-cell therapies in an immunocompetent, outbred animal model may improve our ability to predict their safety and efficacy prior to conducting studies in humans. PMID:25198528

  6. Construct canine intracranial aneurysm model by endovascular technique

    International Nuclear Information System (INIS)

    Liang Xiaodong; Liu Yizhi; Ni Caifang; Ding Yi

    2004-01-01

    Objective: To construct canine bifurcation aneurysms suitable for evaluating the exploration of endovascular devices for interventional therapy by endovascular technique. Methods: The right common carotid artery of six dogs was expanded with a pliable balloon by means of endovascular technique, then embolization with detached balloon was taken at their originations DAS examination were performed on 1, 2, 3 d after the procedurse. Results: 6 aneurysm models were created in six dogs successfully with the mean width and height of the aneurysms decreasing in 3 days. Conclusions: This canine aneurysm model presents the virtue in the size and shape of human cerebral bifurcation saccular aneurysms on DSA image, suitable for developing the exploration of endovascular devices for aneurismal therapy. The procedure is quick, reliable and reproducible. (authors)

  7. Duchenne Muscular Dystrophy Gene Therapy in the Canine Model

    Science.gov (United States)

    2015-01-01

    Abstract Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model. PMID:25710459

  8. A canine distemper model of virus-induced anergy.

    Science.gov (United States)

    Mangi, R J; Munyer, T P; Krakowka, S; Jacoby, R O; Kantor, F S

    1976-05-01

    For development of an animal model of virus-induced anergy, the effect of canine distemper virus (CDV) upon cell-mediated immunity in dogs was investigated. First, canine cutaneous reactions and in vitro lymphocyte responses to soluble protein antigens were characterized. Dogs immunized with picryl guinea pig albumin and with keyhole limpet hemocyanin (both in complete Freund's adjuvant) responded reproducibly to intracutaneous challenge with these antigens. Reactivity peaked in 20-40 days (maximal induration, 6-50 mm). Lymphocytes from these animals responded in vitro to stimulation with keyhole limpet hemocyanin or purified protein derivative. This stimulation was antigen-specific and was maximal on day 6 of culture. Infection with CDV depressed cutaneous reactivity and lymphocyte response in vitro to antigens and mitogens. This effect was transient in animals previously vaccinated with attenuated CDV; however, gnotobiotic puppies (susceptible to CDV) had prolonged depression of cell-mediated immunity and lymphopenia. Some of these animals developed neurologic symptoms and died. The findings indicate that CDV infection is a potentially useful model for study of virus-induced depression of T (thymus)-cell responses and support the hypothesis that there is more than one mechanism responsible for this phenomenon.

  9. Constructing canine carotid artery stenosis model by endovascular technique

    International Nuclear Information System (INIS)

    Cheng Guangsen; Liu Yizhi

    2005-01-01

    Objective: To establish a carotid artery stenosis model by endovascular technique suitable for neuro-interventional therapy. Methods: Twelve dogs were anesthetized, the unilateral segments of the carotid arteries' tunica media and intima were damaged by a corneous guiding wire of home made. Twenty-four carotid artery stenosis models were thus created. DSA examination was performed on postprocedural weeks 2, 4, 8, 10 to estimate the changes of those stenotic carotid arteries. Results: Twenty-four carotid artery stenosis models were successfully created in twelve dogs. Conclusions: Canine carotid artery stenosis models can be created with the endovascular method having variation of pathologic characters and hemodynamic changes similar to human being. It is useful for further research involving the new technique and new material for interventional treatment. (authors)

  10. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

    Directory of Open Access Journals (Sweden)

    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  11. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Science.gov (United States)

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  12. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  13. Bone compaction enhances implant fixation in a canine gap model

    DEFF Research Database (Denmark)

    Kold, Søren; Rahbek, Ole; Toft, Marianne

    2005-01-01

    A new bone preparation technique, compaction, has increased fixation of implants inserted with exact-fit or press-fit to bone. Furthermore, a demonstrated spring-back effect of compacted bone might be of potential value in reducing the initial gaps that often exist between clinical inserted...... implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm...... that the beneficial effect of reduced gap size, as compacted bone springs back, is not eliminated by an impaired gap-healing of compacted bone....

  14. Wound healing modulators in a tracheoplasty canine model.

    Science.gov (United States)

    Olmos-Zúñiga, J Raúl; Hernández-Jiménez, Claudia; Díaz-Martínez, Emmanuel; Jasso-Victoria, Rogelio; Sotres-Vega, Avelina; Gaxiola-Gaxiola, Miguel O; Villalba-Caloca, Jaime; Baltazares-Lipp, Matilde; Santillán-Doherty, Patricio; Santibáñez-Salgado, J Alfredo

    2007-01-01

    Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.

  15. Canine as a biomedical research model: immunological, hematological, and oncological aspects

    International Nuclear Information System (INIS)

    Shifrine, M.; Wilson, F.D.

    1980-01-01

    The canine has been used as a biomedical research model in radiation studies by a number of laboratories supported primarily by the US Department of Energy and its predecessors. These studies were unique in that they covered the life spans of the canines and permitted the collection of data from birth to death under controlled conditions. Since these were multiparametric studies, an extensive data base has been established, not the least of which are normative values covering all biologic systems, including immunohematology. The canine model has also been extensively used by other groups, such as transplantation biologists. The virtues of the canine as a model in these and many other endeavors are becoming increasingly more apparent with the passing of time. One of the primary goals of this volume was to compile the knowledge and experience of researchers using the canine model and to focus their expertise on furthering the use of the canine for studies in immunology, hematology, and oncology. We have attempted to present some of the contemporary, diverse uses of the canine in biomedical research, emphasizing immunologic endpoints, and also to present in detail some of the latest technology used in such studies

  16. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    OpenAIRE

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  17. Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

    Science.gov (United States)

    Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

    2017-08-01

    Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Irradiation inhibits vascular anastomotic stenosis in a canine model

    International Nuclear Information System (INIS)

    Saito, Takeshi; Iguchi, Atsushi; Tabayashi, Koichi

    2009-01-01

    The graft patency rate after coronary artery bypass grafting (CABG) correlates with anastomotic stenosis. Intracoronary radiation therapy is effective for preventing restenosis after percutaneous coronary intervention (PCI). We postulated that intracoronary radiation therapy could prevent anastomotic stenosis and tested this hypothesis in an animal model. Femoral arteries and veins of beagle dogs were harvested, and composite arterioarterial and arteriovenous grafts were prepared. After external irradiation of the anastomotic sites, these composite grafts were transplanted into femoral arteries. Histomorphometric and immunohistological analyses of the anastomotic sites were performed. The study groups consisted of controls and animals exposed to 10 Gy, 20 Gy, and 30 Gy (n=5, in each group). In the artery graft model, the ratio of negative remodeling was significantly increased in all groups exposed to ≥10 Gy. The ratio of neointimal hyperplasia was significantly decreased in all groups exposed to ≥10 Gy. Cell density of anti-α-actin antibody-positive cells and anti-proliferating cell nuclear antigen (PCNA) antibody-positive cells was highest in the adventitial layer, and the density decreased as the dosage increased. Experimental results were almost the same in the vein graft models as in the artery graft models. With double immunohistostaining, the anti-PCNA antibody-positive cells expressed α-actin. Irradiation can inhibit anastomotic stenosis in a canine model. Adventitia is a factor in the creation of stenosis, and irradiation appears to target the adventitia. We speculate that there might be a possible role for intracoronary irradiation in the future to prevent anastomotic stenosis. (author)

  19. Stabilization of multiple rib fractures in a canine model.

    Science.gov (United States)

    Huang, Ke-Nan; Xu, Zhi-Fei; Sun, Ju-Xian; Ding, Xin-Yu; Wu, Bin; Li, Wei; Qin, Xiong; Tang, Hua

    2014-12-01

    Operative stabilization is frequently used in the clinical treatment of multiple rib fractures (MRF); however, no ideal material exists for use in this fixation. This study investigates a newly developed biodegradable plate system for the stabilization of MRF. Silk fiber-reinforced polycaprolactone (SF/PCL) plates were developed for rib fracture stabilization and studied using a canine flail chest model. Adult mongrel dogs were divided into three groups: one group received the SF/PCL plates, one group received standard clinical steel plates, and the final group did not undergo operative fracture stabilization (n = 6 for each group). Radiographic, mechanical, and histologic examination was performed to evaluate the effectiveness of the biodegradable material for the stabilization of the rib fractures. No nonunion and no infections were found when using SF-PCL plates. The fracture sites collapsed in the untreated control group, leading to obvious chest wall deformity not encountered in the two groups that underwent operative stabilization. Our experimental study shows that the SF/PCL plate has the biocompatibility and mechanical strength suitable for fixation of MRF and is potentially ideal for the treatment of these injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma.

    Science.gov (United States)

    Fowles, Jared S; Brown, Kristen C; Hess, Ann M; Duval, Dawn L; Gustafson, Daniel L

    2016-02-19

    Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. The best doxorubicin model involved genes identified in human lines that were co-expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research.

  2. Establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery

    International Nuclear Information System (INIS)

    Cui Xuee; Li Minghua; Wang Yongli; Cheng Yingsheng; Li Wenbin

    2005-01-01

    Objective: To study the feasibility of establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery (CCA) by end-to-end anastomoses of one side common carotid artery segment with the other side common carotid artery. Methods: Surgical techniques were used to make siphon model in 8 canines. One side CCA was taken as the parent artery and anastomosing with the cut off contra-lateral CCA segment which has passed through within the S-shaped glass tube. Two weeks after the creation of models angiography showed the model siphons were patent. Results: Experimental models of human internal carotid artery siphon segment were successfully made in all 8 dogs. Conclusions: It is practically feasible to establish experimental canine common carotid artery models of siphon segment simulating human internal carotid artery. (authors)

  3. Saphenous Venous Ablation with Hot Contrast in a Canine Model

    International Nuclear Information System (INIS)

    Prasad, Amit; Qian Zhong; Kirsch, David; Eissa, Marna; Narra, Pavan; Lopera, Jorge; Espinoza, Carmen G.; Castaneda, Wifrido

    2008-01-01

    Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected under fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used

  4. Does Loading Influence the Severity of Cartilage Degeneration in the Canine Groove-Model of OA?

    NARCIS (Netherlands)

    Vos, Petra; Intema, Femke; van El, Benno; DeGroot, Jeroen; Bijlsma, J. W. J.; Lafeber, Floris; Mastbergen, Simon

    2009-01-01

    Many animal models are used to study osteoarthritis (OA). In these models the role of joint loading in the development of CA is not fully understood. We studied the effect of loading on the development of CIA in the canine Groove-model. In ten female beagle dogs OA was induced in one knee according

  5. Coralline hydroxyapatite bone graft substitutes in a canine metaphyseal defect model: Radiographic-biomechanical correlation

    International Nuclear Information System (INIS)

    Sartoris, D.J.; Resnick, D.; Holmes, R.E.; Tencer, A.F.; Texas Univ., Dallas; Mooney, V.

    1986-01-01

    Radiographic and biomechanical assessment of a new type of bone graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material and autogenous iliac crest graft were implanted, respectively, into the right and left proximal tibial metaphyses of eight dogs. Qualitative and quantitative radiographic evaluation was performed in the immediate postoperative period and at 6 months after surgery. Biomechanical testing was carried out on all grafts following harvest at 6 months, as well as on nonimplanted coralline hydroxyapatite and autogenous iliac cancellous bone. In contrast to autografts, incorporation of coralline implants was characterized by predictable osseous growth and apposition with preservation of intrinsic architecture. Greater percent increase in radiography density, higher ultimate compressive strength, and lower stiffness with incorporation were documented advantages of coralline hydroxyapatite over autogenous graft. Densitometric measurements correlated moderately with strength for both types of graft material (r=0.65). These promising results have important implications to the clinical application of coralline hydroxyapatite bone graft substitutes as an alternative to autogenous grafting. (orig.)

  6. Hypercapnic Acidosis Preserves Gastric Mucosal Microvascular Oxygen Saturation in a Canine Model of Hemorrhage.

    NARCIS (Netherlands)

    Schwartges, Ingo; Picker, Olaf; Beck, Christopher; Scheeren, Thomas W. L.; Schwarte, Lothar A.

    2010-01-01

    The authors aimed to clarify the effects of hypercapnic acidosis and its timing on gastric mucosal oxygenation in a canine model of hemorrhage. This was designed as a prospective, controlled, randomized animal study set in a university research laboratory. Five chronically instrumented dogs were

  7. Canine gastritis.

    Science.gov (United States)

    Webb, Craig; Twedt, David C

    2003-09-01

    Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

  8. Experimental study of pulmonary thromboembolism ischemia-reperfusion injury in canine model

    International Nuclear Information System (INIS)

    Li Jianjun; Zhai Renyou; Zhang Dongpo; Huang Qiang; Yu Ping; Dai Dingke; Bao Na

    2009-01-01

    Objective: To establish a canine model of pulmonary thromboembolism ischemia- reperfusion injury (PTE IRI) that may be used for imaging study. Methods: Ten male and 10 female healthy mongrel canines with (18.6±0.8) kg/body weight, were used. A Swan-Ganz catheter was introduced into the right internal jugular vein via a preset percutaneous sheath using the Seldinger technique, and then was with further insertion the pulmonary artery. Balloon occlusion of the right inferior lobe pulmonary artery for 4 hours was followed by removing the catheter and ending with 4 hours of reperfusion. CT was performed before ischemia, 4 h after ischemia and 4 h after reperfusion. At last, dogs were killed and the bilateral inferior lung tissues were prepared for the examination by light and electronic microscopy. Results: All canine models were successfully developed pulmonary thromboembolism ischemia-reperfusion injury. The examination of CT, light and electron microscopy consistently indicated the presence of permeability pulmonary edema after reperfusion. Conclusions: A closed-chest canine model in vivo of pulmonary thromboembolism ischemia-reperfusion injury can be established with virtual pathophysiological process in human and be as well as for imaging experimental study. (authors)

  9. A novel method for objective vision testing in canine models of inherited retinal disease.

    Science.gov (United States)

    Gearhart, Patricia M; Gearhart, Chris C; Petersen-Jones, Simon M

    2008-08-01

    The use of canine models of retinal disease in the development of therapeutic strategies for inherited retinal disorders is a growing area of research. To evaluate accurately the success of potential vision-enhancing treatments, reliable methods for objectively assessing visual function in canine models is necessary. A simple vision-testing device was constructed that consisted of a junction box with four exit tunnels. Dogs were placed in the junction box and given one vision-based choice for exit. The first-choice tunnel and time to exit were recorded and analyzed. Two canine models of retinal disease with distinct molecular defects, a null mutation in the gene encoding the alpha subunit of rod cyclic GMP phosphodiesterase (PDE6A), and a null mutation in the gene encoding a retinal pigment epithelium-specific protein (RPE65) were tested and compared to those in unaffected dogs. With the use of bright light versus dim red light, the test differentiated between unaffected dogs and dogs affected with either mutation with a high degree of certainty. The white-light intensity series showed a significantly different performance between the unaffected and affected dogs. A significant difference in performance was detected between the dogs with each mutation. The results indicate that this novel canine vision-testing method is an accurate and sensitive means of distinguishing between unaffected dogs and dogs affected with two different forms of inherited retinal disease and should be useful as a means of assessing response to therapy in future studies.

  10. Shared Curriculum Model: A Promising Practice for Education Transformation.

    Science.gov (United States)

    Close, Liz; Gorski, Mary Sue; Sroczynski, Maureen; Farmer, Pat; Wortock, Jean

    2015-12-01

    The shared curriculum model is one of four successful models of academic progression identified through a consensus-building process facilitated by The Future of Nursing: Campaign for Action, with support from the Robert Wood Johnson Foundation, AARP, and the AARP Foundation. Seamless academic progression from the associate degree in nursing (ADN) to the baccalaureate degree in nursing (BSN) is achieved either by simultaneously revising both ADN and BSN curricula or by making targeted adjustments in ADN or BSN curricula to create a unified academic progression. Systematic vetting and definitive agreement on nursing prerequisites and corequisites, general education courses, nursing major content, and general degree requirements are necessary to ensure coordinated degree progression. A standardized set of expectations for beginning professional practice and for unique baccalaureate nursing knowledge ensures vital nursing content across the ADN-to-BSN continuum. Examples of state and regional ADN-to-BSN progression programs using the shared curriculum model are highlighted. The shared curriculum model is a promising practical and sustainable approach to seamless ADN-to-BSN academic progression. Copyright 2015, SLACK Incorporated.

  11. The importance of regional models in assessing canine cancer incidences in Switzerland.

    Science.gov (United States)

    Boo, Gianluca; Leyk, Stefan; Brunsdon, Christopher; Graf, Ramona; Pospischil, Andreas; Fabrikant, Sara Irina

    2018-01-01

    Fitting canine cancer incidences through a conventional regression model assumes constant statistical relationships across the study area in estimating the model coefficients. However, it is often more realistic to consider that these relationships may vary over space. Such a condition, known as spatial non-stationarity, implies that the model coefficients need to be estimated locally. In these kinds of local models, the geographic scale, or spatial extent, employed for coefficient estimation may also have a pervasive influence. This is because important variations in the local model coefficients across geographic scales may impact the understanding of local relationships. In this study, we fitted canine cancer incidences across Swiss municipal units through multiple regional models. We computed diagnostic summaries across the different regional models, and contrasted them with the diagnostics of the conventional regression model, using value-by-alpha maps and scalograms. The results of this comparative assessment enabled us to identify variations in the goodness-of-fit and coefficient estimates. We detected spatially non-stationary relationships, in particular, for the variables related to biological risk factors. These variations in the model coefficients were more important at small geographic scales, making a case for the need to model canine cancer incidences locally in contrast to more conventional global approaches. However, we contend that prior to undertaking local modeling efforts, a deeper understanding of the effects of geographic scale is needed to better characterize and identify local model relationships.

  12. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    McLeod DS

    2016-05-01

    Full Text Available D Scott McLeod, Gerard A Lutty Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA Abstract: Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF. Keywords: angioblasts, blood vessels, endothelial cells, oxygen, retinopathy, retina, vascular endothelial cell growth factor

  13. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.

    Science.gov (United States)

    McLeod, D Scott; Lutty, Gerard A

    2016-01-01

    Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.

  14. Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model

    Science.gov (United States)

    Simão, Daniel; Pinto, Catarina; Fernandes, Paulo; Peddie, Christopher J.; Piersanti, Stefania; Collinson, Lucy M.; Salinas, Sara; Saggio, Isabella; Schiavo, Giampietro; Kremer, Eric J.; Brito, Catarina; Alves, Paula M.

    2017-01-01

    Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in pre-clinical tests. For clinical translation, in-depth pre-clinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, while human adenovirus type 5 (HAdV5) showed increased tropism towards glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity. PMID:26181626

  15. Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

    Science.gov (United States)

    Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

    2012-12-01

    The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing Ltd.

  16. Development of an Arthroscopic Joint Capsule Injury Model in the Canine Shoulder.

    Directory of Open Access Journals (Sweden)

    David Kovacevic

    Full Text Available The natural history of rotator cuff tears can be unfavorable as patients develop fatty infiltration and muscle atrophy that is often associated with a loss of muscle strength and shoulder function. To facilitate study of possible biologic mechanisms involved in early degenerative changes to rotator cuff muscle and tendon tissues, the objective of this study was to develop a joint capsule injury model in the canine shoulder using arthroscopy.Arthroscopic surgical methods for performing a posterior joint capsulectomy in the canine shoulder were first defined in cadavers. Subsequently, one canine subject underwent bilateral shoulder joint capsulectomy using arthroscopy, arthroscopic surveillance at 2, 4 and 8 weeks, and gross and histologic examination of the joint at 10 weeks.The canine subject was weight-bearing within eight hours after index and follow-up surgeries and had no significant soft tissue swelling of the shoulder girdle or gross lameness. Chronic synovitis and macroscopic and microscopic evidence of pathologic changes to the rotator cuff bony insertions, tendons, myotendinous junctions and muscles were observed.This study demonstrates feasibility and proof-of-concept for a joint capsule injury model in the canine shoulder. Future work is needed to define the observed pathologic changes and their role in the progression of rotator cuff disease. Ultimately, better understanding of the biologic mechanisms of early progression of rotator cuff disease may lead to clinical interventions to halt or slow this process and avoid the more advanced and often irreversible conditions of large tendon tears with muscle fatty atrophy.

  17. Solutions for Failing High Schools: Converging Visions and Promising Models.

    Science.gov (United States)

    Legters, Nettie; Balfanz, Robert; McPartland, James

    Promising solutions to the failings of traditional comprehensive high schools were reviewed to identify basic principles and strategies for improving high schools nationwide. Selected research studies, policy documents, and promising high school programs were reviewed. The review revealed the following principles for helping high schools better…

  18. The establishment of bilateral external iliac artery stenosis model in experimental canines and its angiographic evaluation

    International Nuclear Information System (INIS)

    Xia Yonghui; Li Weixiao; Bi Yonghua; Xu Ke

    2011-01-01

    Objective: To establish an experimental canine model of bilateral external iliac artery stenosis by surgical method with absorbable suture. Methods: Under general anesthesia bilateral external iliac arteries were partly obstructed (about 50%) with absorbable suture in ten dogs. Three months later angiography was performed to evaluate the arterial stricture degree. Results: Bilateral external iliac artery stenosis model was successfully established in eight dogs and the other two dogs died within two weeks after the procedure. Angiography performed three months after the procedure showed that the stricture degree of arterial lumen was (60.6±12.5)%. Conclusion: Satisfactory experimental canine model of bilateral external iliac artery stenosis can be established by surgical method with absorbable suture. This method can be used for reference when peripheral artery stenosis model is to be prepared in larger animals. (authors)

  19. Video Self-Modeling: A Promising Strategy for Noncompliant Children.

    Science.gov (United States)

    Axelrod, Michael I; Bellini, Scott; Markoff, Kimberly

    2014-07-01

    The current study investigated the effects of a Video Self-Modeling (VSM) intervention on the compliance and aggressive behavior of three children placed in a psychiatric hospital. Each participant viewed brief video clips of himself following simple adult instructions just prior to the school's morning session and the unit's afternoon free period. A multiple baseline design across settings was used to evaluate the effects of the VSM intervention on compliance with staff instructions and aggressive behavior on the hospital unit and in the hospital-based classroom. All three participants exhibited higher levels of compliance and fewer aggressive episodes during the intervention condition, and the effects were generally maintained when the intervention was withdrawn. Hospital staff reported at the conclusion of the study that the VSM intervention was easy to implement and beneficial for all participants. Taken altogether, the results suggest VSM is a promising, socially acceptable, and proactive intervention approach for improving the behavior of noncompliant children. © The Author(s) 2014.

  20. Canine intrahepatic vasculature: is a functional anatomic model relevant to the dog?

    Science.gov (United States)

    Hall, Jon L; Mannion, Paddy; Ladlow, Jane F

    2015-01-01

    To clarify canine intrahepatic portal and hepatic venous system anatomy using corrosion casting and advanced imaging and to devise a novel functional anatomic model of the canine liver to investigate whether this could help guide the planning and surgical procedure of partial hepatic lobectomy and interventional radiological procedures. Prospective experimental study. Adult Greyhound cadavers (n = 8). Portal and hepatic vein corrosion casts of healthy livers were assessed using computed tomography (CT). The hepatic lobes have a consistent hilar hepatic and portal vein supply with some variation in the number of intrahepatic branches. For all specimens, 3 surgically resectable areas were identified in the left lateral lobe and 2 surgically resectable areas were identified in the right medial lobe as defined by a functional anatomic model. CT of detailed acrylic casts allowed complex intrahepatic vascular relationships to be investigated and compared with previous studies. Improving understanding of the intrahepatic vascular supply facilitates interpretation of advanced images in clinical patients, the planning and performance of surgical procedures, and may facilitate interventional vascular procedures, such as intravenous embolization of portosystemic shunts. Functional division of the canine liver similar to human models is possible. The left lateral and right medial lobes can be consistently divided into surgically resectable functional areas and partial lobectomies can be performed following a functional model; further study in clinically affected animals would be required to investigate the relevance of this functional model in the dog. © Copyright 2014 by The American College of Veterinary Surgeons.

  1. Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

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    Sathidpak Nantasanti

    2015-11-01

    Full Text Available The recent development of 3D-liver stem cell cultures (hepatic organoids opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease.

  2. Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

    Science.gov (United States)

    Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

    2013-03-01

    To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

  3. Establishment and bronchial arteriography of the models of canine lung cancer

    International Nuclear Information System (INIS)

    Cao Xicai; Wang Xiaodong; Li Bin; Shi Jianguang; Liu Yong; Xu Nanxun; Ma Weijun; Yang Haixian; Bai Jingwen; Li Weidong; Liu Shuping; Liu Anpu

    2003-01-01

    Objective: To investigate the establishment and bronchial arteriography of the models of canine lung cancer, and to facilitate further diagnosis and treatment of lung cancer. Methods: Twenty-two dogs were respectively administrated with 3 ml suspension of lipiodol-ultrafluid mixed with 3- methylcholanthrene (MCA) and diethylnitrosamine (DEN). The suspension was injected into the diaphragmic lobe of right lung with the co-axial catheter through endotracheal intubation. The dogs were randomly divided into 5 groups, group A (4 dogs), B (4), C (4), D (5), and E (5), which were sacrificed after observation for 1, 3, 6, 12, and 18 months, respectively. Then the image analysis and histopathologic examinations were carried out at different period. 5 dogs in group E were examined by bronchial arteriography. Results: Peribronchiolitis and atelectasis appeared at early stage (one month). Chronic granulomatous inflammation and fibrosis of lung tissue were gradually formed after 3 months. Proliferation of stem cells in bronchioles and atypical hyperplasia were found from 6 to 12 months. At last, the squamous carcinoma and bronchioloalveolar carcinoma were induced after 18 months. The lung cancer and precancerous lesion were found in 4 of 5 dogs at the 18 th month. The bronchial arteriography in the 5 dogs showed that 3 bronchial arteries were found as the supplying blood artery to the tumor. Conclusion: The suspension of lipiodol-ultrafluid mixed with MCA and DEN was exactly injected with the co-axial catheter through endotracheal intubation to establish the models of canine lung cancer. The inducible rate of the method was high and the location of lung cancer was accurate. It was affirmed that the blood supply artery of canine lung cancer was bronchial artery. Bronchial arteriography was of momentous significance to the diagnosis of early lung cancer. The establishment of the models of canine lung cancer was significant in the diagnosis and treatment of lung cancer. The models

  4. Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Yu, Long; Zhou, Zhaoye; Killingsworth, Cheryl R; He, Bin

    2015-01-15

    Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs. Copyright © 2015 the American Physiological Society.

  5. An experimental in-vivo canine model for adult shunt infection

    Directory of Open Access Journals (Sweden)

    Procop Gary

    2008-10-01

    Full Text Available Abstract Background Detailed human studies of the mechanisms and development of shunt infection in real time are not possible, and we have developed a canine hydrocephalus model to overcome this. The intention of this pilot study was to show that the canine hydrocephalus model could be shunted using conventional "human" shunts, and that a shunt infection could be established so that further studies could then be planned. Methods Hydrocephalus was induced in seven dogs (Canis familiaris by fourth ventricle obstruction. Four weeks later they were shunted using a Hakim Precision valve. Four of the dogs received shunts whose ventricular catheter had been inoculated with Staphylococcus epidermidis, and three were uninoculated controls. Four weeks after shunting the dogs were sacrificed and necropsy was performed. Removed shunts and tissue samples were examined microbiologically and isolates were subjected to detailed identification and genomic comparison. Results All the dogs remained well after shunting. Examination of removed shunt components revealed S. epidermidis in the brain and throughout the shunt system in the four inoculated animals, but in two of these Staphylococcus intermedius was also found. S. intermedius was also isolated from all three "negative" controls. There were slight differences between S. intermedius strains suggesting endogenous infection rather than cross- infection from a point source. Conclusion Shunt infection was established in the canine model, and had the experiment been extended beyond four weeks the typical microbiological, pathological and clinical features might have appeared. The occurrence of unplanned shunt infections in control animals due to canine normal skin flora reflects human clinical experience and underlines the usual source of bacteria causing shunt infection.

  6. Prevention approaches in a preclinical canine model of Alzheimer’s disease: Benefits and challenges

    Directory of Open Access Journals (Sweden)

    Paulina R. Davis

    2014-03-01

    Full Text Available Aged dogs spontaneously develop many features of human aging and Alzheimer’s disease (AD including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins. Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g. antioxidants combined with behavioral enrichment. Aging canine studies show good predictive validity for human clinical trials outcomes (e.g. immunotherapy and several interventions tested in dogs strongly support a prevention approach (e.g. immunotherapy and statins. Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3-5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of nonhuman primates. However overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and nonhuman primates.

  7. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  8. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    Science.gov (United States)

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie; Struck, Maggie; Ramirez, Harvey E.; Jordan, Juan; Andrutis, Karl; Chou, Janice Y.; Byrne, Barry J.

    2010-01-01

    Abstract Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-α. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver. PMID:20163245

  9. Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model.

    Science.gov (United States)

    Ng, Kenneth W; Lima, Eric G; Bian, Liming; O'Conor, Christopher J; Jayabalan, Prakash S; Stoker, Aaron M; Kuroki, Keiichi; Cook, Cristi R; Ateshian, Gerard A; Cook, James L; Hung, Clark T

    2010-03-01

    It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors) adult chondrocytes from three adult dogs were encapsulated in agarose, and cultured in serum-free media with transforming growth factor-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in glycosaminoglycan content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and glycosaminoglycan content in the range of native adult canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects.

  10. Biomechanical characteristics of self-ligating brackets in a vertically displaced canine model: a finite element analysis.

    Science.gov (United States)

    Kim, S-J; Kwon, Y-H; Hwang, C-J

    2016-05-01

    The objective of this study was to compare the biomechanical characteristics between two types of self-ligating brackets and conventional metal brackets using finite element analysis of a vertically displaced canine model focusing on the desired force on the canine and undesirable forces on adjacent teeth. Three-dimensional finite element models of the maxillary dentition with 1-mm, 2-mm, and 3-mm vertically displaced canines were constructed. Two different self-ligating brackets (In-Ovation C and Smart clip) and a conventional metal bracket (Micro-arch) were modeled. After a 0.016-inch NiTi (0.40 mm, round) wire was engaged, the displacement of each tooth was calculated using x-, y-, and z-coordinates, and the tensile and compressive stresses were calculated. The extrusion and maximal tensile stress of the canine differed little between the three brackets, but the intrusion and minimal compressive stress values of the adjacent teeth differed considerably and were highest in the Smart clip and least in the In-Ovation C. The extrusion and maximal tensile stress of the canine in the 3-mm displacement model was less than that in the 2-mm displacement model, and the intrusion and minimal compressive stress of the adjacent teeth increased with the degree of displacement. Self-ligating brackets were not superior to conventional brackets in leveling a vertically displaced canine. A continuous arch wire may not be recommended for leveling of severely displaced canines whether using self-ligating or conventional brackets. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Cryoplasty for the treatment of iliac artery stenosis in canine model

    International Nuclear Information System (INIS)

    Wu Zhengzhong; Yang Weizhu; Jiang Na; Zheng Qubin; Huang Keyao; Huang Ning; Shen Quan

    2013-01-01

    Objective To evaluate the treatment effect of balloon angioplasty and cryoplasty on iliac artery stenosis in canine model. Methods: Canine models of iliac artery stenosis were established with surgical ligation and transfixion. Models were randomly divided into two groups: iliac artery stenosis treated by cryoplasty (n = 8) and by balloon angioplasty (n = 8). The degree of iliac artery stenosis of two model groups was assessed by digital subtraction angiography (DSA) immediately and two weeks after the angioplasties. Then all the dogs were executed for pathological observation of the target vessels. Results: Sixteen canine models of iliac artery stenosis were established by surgical ligation and transfixion method with 100% success rate. DSA showed there was (45 ± 12)% of residual artery stenosis in the cryoplasty group immediately after surgery, while it was (39-12)% in the balloon angioplasty group, and there was no significant difference between them (t = 3.183, P > 0.05). The artery stenosis of cryoplasty group was (48 ± 17)% after two weeks and not significantly different from that after surgery immediately (t = -1.271, P > 0.05). The artery stenosis of balloon angioplasty group was (67 ± 13)% after two weeks, and it was significantly higher compared with at after surgery immediately (t = -6.666, P < 0.01). The degree of vascular stenosis in balloon angioplasty group was severer than that in cryoplasty group two weeks after angiography (P = 0.041). The pathological examination showed artery intimal hyperplasia in cryoplasty group was milder than that in balloon angioplasty group and neointimal content of collagen in cryoplasty group was less than that in balloon angioplasty group. Conclusions: The animal models of iliac artery stenosis were established successfully with surgical ligation and transfixion by damaging the intima and media of arterial wall. Compared with balloon angioplasty, the cryoplasty was able to inhibit proliferation of intimal and reduce

  12. Experimental studies on canine terminal carotid arterial aneurysm models pre- and post-embolized with microcoil

    International Nuclear Information System (INIS)

    Wang Qihong; Zhou Liangfu; Gong Jianqiu; Dai Jianhua; Zhang Xiaojun; Zhang Xinyuan

    2005-01-01

    Objective: To establish canine terminal saccular aneurysm model of common carotid artery (CCA), and evaluate the images and hemodynamic changes of aneurysm cavities pre- and post-embolized with microcoil (MC). Methods: Seven CCA terminal saccular aneurysm models had been created by using improved microsurgical technique. Seven to fourteen days after surgery, models were undergone color Doppler, Magnetic resonance image (MRI), Magnetic resonance angiography (MRA), digital subtraction angiography (DSA), and then the analysis of computational fluid dynamics (CFD) on these animal models were conducted. Afterwards they were compactly packed with MC, and then aneurysms again were examed under these methods, and simulation of pathological changes. Results: Models were created successfully with good MC compactly pack aneurysm cavities. DSA combined with other imaging methods can improve the diagnosis of aneurysms completely. CFD models can show the imitation hemodynamics of canine carotid aneurysms. Conclusions: This kind of aneurysm model is an ideal one on the area for the research of aneurysm embolization. Non-DSA imaging examination can noninvasively, repeatedly, clearly evaluate aneurysms pre- and post-embolized with MC. The interference on the inflow zone of the aneurysm is an effective method for cure and preventing recurrence of aneurysms. (authors)

  13. A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

    NARCIS (Netherlands)

    Y.H. Sniekers (Yvonne); F. Intema (Femke); F.P.J.G. Lafeber (Floris); G.J.V.M. van Osch (Gerjo); J.P.T.M. van Leeuwen (Hans); H.H. Weinans (Harrie); S.C. Mastbergen (Simon)

    2008-01-01

    textabstractBACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point

  14. Probabilistic language models in cognitive neuroscience: Promises and pitfalls.

    Science.gov (United States)

    Armeni, Kristijan; Willems, Roel M; Frank, Stefan L

    2017-12-01

    Cognitive neuroscientists of language comprehension study how neural computations relate to cognitive computations during comprehension. On the cognitive part of the equation, it is important that the computations and processing complexity are explicitly defined. Probabilistic language models can be used to give a computationally explicit account of language complexity during comprehension. Whereas such models have so far predominantly been evaluated against behavioral data, only recently have the models been used to explain neurobiological signals. Measures obtained from these models emphasize the probabilistic, information-processing view of language understanding and provide a set of tools that can be used for testing neural hypotheses about language comprehension. Here, we provide a cursory review of the theoretical foundations and example neuroimaging studies employing probabilistic language models. We highlight the advantages and potential pitfalls of this approach and indicate avenues for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Pan-nitinol occluder and special delivery device for closure of patent ductus arteriosus: a canine-model feasibility study.

    Science.gov (United States)

    Jiang, Hai-bin; Bai, Yuan; Zong, Gang-jun; Han, Lin; Li, Wei-ping; Lu, Yang; Qin, Yong-wen; Zhao, Xian-xian

    2013-01-01

    The aim of this study was to evaluate a new type of occluder for patent ductus arteriosus. Patent ductus arteriosus was established in a canine model by anastomosing a length of autologous jugular vein to the descending aorta and the left pulmonary artery in an end-to-side fashion. Transcatheter closure of each patent ductus arteriosus was performed on 10 dogs, which were then monitored for as long as 6 months with aortography, echocardiography, and histologic evaluation. Transcatheter closure with use of the novel pan-nitinol device was successful in all canine models. Postoperative echocardiography showed that the location and shape of the occluders were normal, without any residual shunting. Further histologic evaluation confirmed that the occluder surface was completely endothelialized 3 months after implantation. Transcatheter patent ductus arteriosus closure with the pan-nitinol occluder can be performed safely and successfully in a canine model and shows good biological compatibility and low mortality rates.

  16. Silkworm: A Promising Model Organism in Life Science.

    Science.gov (United States)

    Meng, Xu; Zhu, Feifei; Chen, Keping

    2017-09-01

    As an important economic insect, silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) has numerous advantages in life science, such as low breeding cost, large progeny size, short generation time, and clear genetic background. Additionally, there are rich genetic resources associated with silkworms. The completion of the silkworm genome has further accelerated it to be a modern model organism in life science. Genomic studies showed that some silkworm genes are highly homologous to certain genes related to human hereditary disease and, therefore, are a candidate model for studying human disease. In this article, we provided a review of silkworm as an important model in various research areas, including human disease, screening of antimicrobial agents, environmental safety monitoring, and antitumor studies. In addition, the application potentiality of silkworm model in life sciences was discussed. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  17. A Canine Non-Weight-Bearing Model with Radial Neurectomy for Rotator Cuff Repair.

    Directory of Open Access Journals (Sweden)

    Xiaoxi Ji

    Full Text Available The major concern of using a large animal model to study rotator cuff repair is the high rate of repair retears. The purpose of this study was to test a non-weight-bearing (NWB canine model for rotator cuff repair research.First, in the in vitro study, 18 shoulders were randomized to 3 groups. 1 Full-width transections repaired with modified Mason-Allen sutures using 3-0 polyglactin suture, 2 Group 1 repaired using number 2 (#2 polyester braid and long-chain polyethylene suture, and 3 Partial-width transections leaving the superior 2 mm infraspinatus tendon intact without repair. In the in vivo study of 6 dogs, the infraspinatus tendon was partially transected as the same as the in vitro group 3. A radial neurectomy was performed to prevent weight bearing. The operated limb was slung in a custom-made jacket for 6 weeks.In the in vitro study, mean ultimate tensile load and stiffness in Group 2 were significantly higher than Group 1 and 3 (p<0.05. In the in vivo study, gross inspection and histology showed that the preserved superior 2-mm portion of the infraspinatus tendon remained intact with normal structure.Based on the biomechanical and histological findings, this canine NWB model may be an appropriate and useful model for studies of rotator cuff repair.

  18. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  19. Vascularized bone grafting in a canine carpal avascular necrosis model

    NARCIS (Netherlands)

    Willems, Wouter F.; Alberton, Gregory M.; Bishop, Allen T.; Kremer, Thomas

    2011-01-01

    Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting. A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone. In seven mongrel dogs, AVN was induced by removal of the radial

  20. The Development of a Canine Anorectal Autotransplantation Model Based on Blood Supply: A Preliminary Case Report

    Science.gov (United States)

    Nakamura, Tatsuo; Sato, Tomoyuki; Naito, Munekazu; Fujii, Satoshi; Mihara, Makoto; Koshima, Isao

    2012-01-01

    Colostomy is conventionally the only treatment for anal dysfunction. Recently, a few trials of anorectal transplantation in animals have been published; however, further development of this technique is required. Moreover, it is crucial to perform this research in dogs, which resemble humans in anorectal anatomy and biology. We designed a canine anorectal transplantation model, wherein anorectal autotransplantation was performed by anastomoses of the rectum, inferior mesenteric artery (IMA) and vein, and pudendal nerves. Resting pressure in the anal canal and anal canal pressure fluctuation were measured before and after surgery. Graft pathology was examined three days after surgery. The anal blood supply was compared with that in three beagles using indocyanine green (ICG) fluorescence angiography. The anorectal graft had sufficient arterial blood supply from the IMA; however, the graft’s distal end was congested and necrotized. Functional examination demonstrated reduced resting pressure and the appearance of an irregular anal canal pressure wave after surgery. ICG angiography showed that the pudendal arteries provided more blood flow than the IMA to the anal segment. This is the first canine model of preliminary anorectal autotransplantation, and it demonstrates the possibility of establishing a transplantation model in dogs using appropriate vascular anastomoses, thus contributing to the progress of anorectal transplantation. PMID:22970198

  1. Micro-computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model

    Science.gov (United States)

    Khobragade, P.; Jain, A.; Setlur Nagesh, S. V.; Andreana, S.; Dziak, R.; Sunkara, S. K.; Sunkara, S.; Bednarek, D. R.; Rudin, S.; Ionita, C. N.

    2015-03-01

    High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custombuilt micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor invivo bone regeneration studies for greater regenerative process understanding.

  2. [Effect of benazepril on atrial cytoskeleton remodeling in the canine atrial fibrillation models].

    Science.gov (United States)

    Liu, Li; Qu, Xiu-Fen; Yu, Yang; Bai, Bing; Huang, Yong-Lin

    2009-10-20

    To investigate the effect of benazepril on atrial cytoskeleton remodeling in atrial fibrillation (AF) canines induced by chronic rapid atrial pacing (RAP). Twenty canines were randomly divided into 3 groups: (1) Sham-operated group without RAP; (2) AF group: AF established by RAP at 600 beats per minute for 6 weeks; (3) Benazepril group: benazepril was dosed from 1 week pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was measured, collagen volume fraction (CVF) analyzed by Masson staining and the expression and distribution of desmin were assayed by immunohistochemistry. RT-PCR method was used to semi-quantify the mRNA expression of beta-tubulin and desmin. The diameter of atrial cardiomyocyte increased in AF group [LA:(27.9 +/- 3.8) microm; RA: (26.8 +/- 3.2) microm] and benazepril group[LA: (25.1 +/- 3.4) microm; RA: (25.2 +/- 3.5) microm] than sham-operated group [LA: (19.6 +/- 2.9) microm; RA: (18.7 +/- 2.6) microm] (P benazepril group than AF group [LA: (11.3 +/- 0.8)% vs (16.9 +/- 1.1)%, RA: (10.9 +/- 0.8)% vs (15.7 +/- 2.3)%, P benazepril group than AF group (P benazepril group than AF group (LA:0.8 +/- 0.4 vs 1.0 +/- 0.3, 0.7 +/- 0.3 vs 0.9 +/- 0.4; RA:0.7 +/- 0.3 vs 1.0 +/- 0.6, 0.7 +/- 0.3 vs 1.1 +/- 0.3, P Benazepril can favorably improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.

  3. Animal-Assisted Therapy for persons with disabilities based on canine tail language interpretation via fuzzy emotional behavior model.

    Science.gov (United States)

    Phanwanich, Warangkhana; Kumdee, Orrawan; Ritthipravat, Panrasee; Wongsawat, Yodchanan

    2011-01-01

    Animal-Assisted Therapy (AAT) is the science that employs the merit of human-animal interaction to alleviate mental and physical problems of persons with disabilities. However, to achieve the goal of AAT for persons with severe disabilities (e.g. spinal cord injury and amyotrophic lateral sclerosis), real-time animal language interpretation is needed. Since canine behaviors can be visually distinguished from its tail, this paper proposes the automatic real-time interpretation of canine tail language for human-canine interaction in the case of persons with severe disabilities. Canine tail language is captured via two 3-axis accelerometers. Directions and frequency are selected as our features of interests. New fuzzy rules and center of gravity (COG)-based defuzzification method are proposed in order to interpret the features into three canine emotional behaviors, i.e., agitate, happy, and scare as well as its blended emotional behaviors. The emotional behavior model is performed in the simulated dog. The average recognition rate in real dog is 93.75% accuracy.

  4. Power Doppler Imaging in Acute Renal Vein Occlusion and Recanalization: a Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Objective : To evaluate the dynamic changes of the power Doppler (PD) in acute renal vein occlusion and recanalization in a canine model. Materials and Methods : We performed a PD of the kidney during graded renal vein occlusion and recanalization induced by balloon inflation and deflation in nine dogs. The PD images were transferred to a personal computer, and the PD signals were quantified. Result : We observed the temporal change of the PD signal during renal vein occlusion and recanalization, with a decrease in the PD signal during occlusion and an increase during recanalization. The mean PD signal decreased gradually as the renal vein was occluded, and conversely increased gradually with sequential relief of occlusion. The sequential change of the mean value of the PD signal was statistically significant. Conclusion : The PD can detect a change in renal blood flow during acute renal vein occlusion and recanalization in a canine model. The PD may be used as a helpful tool for the early detection of acute renal vein thrombosis and the monitoring of renal perfusion.

  5. Power Doppler Imaging in Acute Renal Vein Occlusion and Recanalization: a Canine Model

    International Nuclear Information System (INIS)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo

    2008-01-01

    Objective : To evaluate the dynamic changes of the power Doppler (PD) in acute renal vein occlusion and recanalization in a canine model. Materials and Methods : We performed a PD of the kidney during graded renal vein occlusion and recanalization induced by balloon inflation and deflation in nine dogs. The PD images were transferred to a personal computer, and the PD signals were quantified. Result : We observed the temporal change of the PD signal during renal vein occlusion and recanalization, with a decrease in the PD signal during occlusion and an increase during recanalization. The mean PD signal decreased gradually as the renal vein was occluded, and conversely increased gradually with sequential relief of occlusion. The sequential change of the mean value of the PD signal was statistically significant. Conclusion : The PD can detect a change in renal blood flow during acute renal vein occlusion and recanalization in a canine model. The PD may be used as a helpful tool for the early detection of acute renal vein thrombosis and the monitoring of renal perfusion

  6. GIS modeling for canine dirofilariosis risk assessment in central Italy

    Directory of Open Access Journals (Sweden)

    Michele Mortarino

    2008-05-01

    Full Text Available A survey was conducted in an area of central Italy in order to study the prevalence of Dirofilaria immitis and D. repens in dogs. Blood samples were collected from 283 dogs and examined using a modified Knott’s technique. In addition, in order to detect D. immitis occult infection, 203 serum samples were also analysed for D. immitis antigen detection. The results were analyzed in order to evaluate the behavioural and attitudinal risk factors. A geographical information system (GIS for the study area was constructed, utilizing the following data layers: administrative boundaries, elevation, temperature, rainfall and humidity. Microfilariae were detected in 32 of the 283 dogs surveyed, constituting a total Dirofilaria prevalence of 11.3%. In particular, 20 dogs (7.1% were positive for D. immitis and 12 dogs (4.2% for D. repens microfilariae. One case of D. immitis occult infection was also detected. Choroplethic municipal maps were drawn within the GIS in order to display the distribution of each Dirofilaria species in the study area. Statistical analysis showed a significant association between Dirofilaria infection and animal attitude (hunting/truffle dogs showed a higher prevalence compared to guard/pet dogs. A higher prevalence was also recorded in 2 to 5-years old dogs. Furthermore a GIS-based modelling of climatic data, collected from 5 meteorological stations in the study area, was performed to estimate the yearly number of D. immitis generations in the mosquito vector. The results of the model as depicted by GIS analysis was highly concordant with the territorial distribution of positive dogs and showed that D. immitis spreading is markedly influenced by season. The potential transmission period in the study area was found to be confined to summer months with a peak in July and August, as expected for a temperate region where summer season is the most favourable period for the parasite.

  7. A canine model of Cohen syndrome: Trapped Neutrophil Syndrome.

    Science.gov (United States)

    Shearman, Jeremy R; Wilton, Alan N

    2011-05-23

    Trapped Neutrophil Syndrome (TNS) is a common autosomal recessive neutropenia in Border collie dogs. We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is VPS13B. We chose VPS13B as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to VPS13B showed positive linkage of the region to TNS. We sequenced each of the 63 exons of VPS13B in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of VPS13B in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28. Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.

  8. A canine model of Cohen syndrome: Trapped Neutrophil Syndrome

    Directory of Open Access Journals (Sweden)

    Shearman Jeremy R

    2011-05-01

    Full Text Available Abstract Background Trapped Neutrophil Syndrome (TNS is a common autosomal recessive neutropenia in Border collie dogs. Results We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is VPS13B. We chose VPS13B as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to VPS13B showed positive linkage of the region to TNS. We sequenced each of the 63 exons of VPS13B in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of VPS13B in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28. Conclusion Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.

  9. A new experimental carotid siphon aneurysm model in canine based on the MR angiography and rapid prototyping technology

    International Nuclear Information System (INIS)

    Xie Jian; Li Minghua; Tan Huaqiao; Zhu Yueqi; Hu Dingjun; Qiao Ruihua; Fan Chunhua

    2009-01-01

    Objective: The aim of the experiment is to make an intracranial aneurysm model in canine. Methods: A digital tube was made based on raw magnetic resonance images of the human intracranial carotid artery. Then 6 tubes were made in the 3D rapid prototyping machine and coated with silicone. Finally we isolated the common carotid arteries of 6 canines and made them go through the tubes and anastomosed them end-to-side to get the aneurysm model. Six stents were implanted after one week. Results: Six aneurysm models were successfully made in canines. The parent artery had similar geometry of the human carotid siphon. All the aneurysms and parent arteries were patent in one week's follow-up. One canine died of excessive anesthesia after stenting. Two vascular models kept patent in one month without stenosis. The other 3 had some stenosis on the bends of the vessel. Conclusions: The aneurysm model in the experiment has high flexibility and reliability. The model provides an effective tool for research and testing neurovascular devices. It's also a useful device to train the neuroradiologists and interventional physicians. (authors)

  10. Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

    Science.gov (United States)

    Kecova, Helga; Harper, Matthew M.; Nilaweera, Wijitha; Kuehn, Markus H.; Kardon, Randy H.

    2010-01-01

    Purpose. To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Methods. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). Results. A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Conclusions. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss. PMID:19661222

  11. Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2016-04-01

    Full Text Available ABSTRACT Purpose: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Materials and Methods: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Results: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039. Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039. Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Conclusions: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

  12. The effects of implant composition on extensor tenosynovitis in a canine distal radius fracture model.

    Science.gov (United States)

    Sinicropi, Stefano M; Su, Brian W; Raia, Frank J; Parisien, May; Strauch, Robert J; Rosenwasser, Melvin P

    2005-03-01

    Dorsal plating of distal radius fractures with titanium plates has resulted in clinically observed tenosynovitis and tendon rupture. The goal of this study was to investigate whether titanium-based implants result in more extensor tendon inflammation than matched stainless-steel implants in a canine fracture model. An osteotomy was created in the distal radius of 18 beagles and fixed with 2.7-mm 4-hole plates composed of commercially pure titanium, titanium alloy (Ti-Al6-V4), or 316L stainless steel. Animals were killed at an average of 4 months. Tendon gliding was assessed by applying a force at the extensor musculotendinous junction and noting gliding. Histologic grading (mild, moderate, severe) was based on cellular hypertrophy, hyperplasia, and leukocytic infiltration. Tendons glided freely in 100% stainless-steel specimens, 75% of titanium alloy, and 43% of commercially pure titanium groups. A severe inflammatory reaction was identified in 60% of the titanium alloy (Ti-A16-V4) group, 57% of the pure titanium group, and 0% of the stainless-steel group. Dorsal plating of the canine radius with commercially pure titanium or titanium alloy implants produced a greater inflammatory peritendinous response than matched stainless-steel implants.

  13. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  14. Manipulation of food intake and weight dynamics using retrograde neural gastric electrical stimulation in a chronic canine model

    NARCIS (Netherlands)

    Aelen, P.; Neshev, E.; Cholette, M.; Crisanti, K.; Mitchell, P.; De bru, E.; Church, N.; Mintchev, M.P.

    2008-01-01

    Neural gastric electrical stimulation (NGES) could be a new technique for treating obesity. However, chronic animal experimentation exploring the efficacy of this therapy is lacking. In this study we investigated the utility of retrograde NGES in a chronic canine model. Nine mongrel dogs (26.8 ± 5.2

  15. Prostate histotripsy for BPH: initial canine results

    Science.gov (United States)

    Roberts, William W.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.

    2009-02-01

    Histotripsy is an extracorporeal ablative technology that utilizes microsecond pulses of intense ultrasound (< 1% duty cycle) to produce nonthermal, mechanical fractionation of targeted tissue. We have previously demonstrated the feasibility of histotripsy prostate ablation. In this study we sought to assess the chronic tissue response, tolerability and safety of histotripsy in a chronic in vivo canine model. Five acute and thirteen chronic canine subjects were anesthetized and treated with histotripsy targeting the prostate. Pulses consisted of 3 cycle bursts of 750 kHz ultrasound at a repetition rate of 300 Hz delivered transabdominally from a highly focused 15 cm aperture array. Transrectal ultrasound imaging provided accurate targeting and real-time monitoring of histotripsy treatment. Prostates were harvested at 0, 7, 28, or 56 days after treatment. Consistent mechanical tissue fractionation and debulking of prostate tissue was seen acutely and at delayed time points without collateral injury. Urothelialization of the treatment cavity was apparent 28 days after treatment. Canine subjects tolerated histotripsy with minimal hematuria or discomfort. Only mild transient lab abnormalities were noted. Histotripsy is a promising non-invasive therapy for prostate tissue fractionation and debulking that appears safe and well tolerated without systemic side effects in the canine model.

  16. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

    Directory of Open Access Journals (Sweden)

    Milcah C. Scott

    2016-12-01

    Full Text Available Osteosarcoma (OS is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2 for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of

  17. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.

    Science.gov (United States)

    Scott, Milcah C; Tomiyasu, Hirotaka; Garbe, John R; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M Gerard; Subramanian, Subbaya; Bryan, Brad A; Modiano, Jaime F

    2016-12-01

    Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. © 2016

  18. Dose-effective investigation of intraarterial r-Sak in canine model with acute cerebral infarctions

    International Nuclear Information System (INIS)

    Liu Sheng; Shi Haibin; Zhang Peng; Wang Chenghu; Zhou Chunguo; Li Linsun

    2007-01-01

    Objective: To compare the effect and complications of intraarterial thrombolysis with different doses of recombinant-staphylokinase (r-Sak) in canine model with acute cerebral infarction, and then to find out the most properly appropriate effective dose. Methods: The model with left cerebral embolism was established with interventional technique in 24 beagle adult dogs. They were randomly divided into 4 groups including control group(saline, 10 ml), group of low dose(r-Sak, 5 000 u/kg), middle dose(r-Sak, 10 000 u/kg) and high dose(r-Sak, 20 000 u/kg). Angiography and intraarterial thrombolysis were performed within 30 minutes after the embolization. Microcatheter was superselectively inserted into left carotid artery. Five hour's later with a repeated angiography at half, 1 and 2 hours after thrombolysis to observe the recanalization. Blood samples were collected at a series of time pre-and post-thrombolysis to test the plasma levels of PT, APTT and D-dimer. These canines were sacrificed, and their cerebri were taken out for pathologic study by the end of 24 hours. Results: The rates of efficacy within 2 hours after thrombolysis were 10.0% (1/10) in control group, 40.0% (4/10) in low dose group, 90.9% (10/11) in middle dose group and 100% (9/9) in high dose group. The rates of complete recanalization were 0, 10% (1/10), 36.4% (4/11) and 66.7% (6/9), correspondingly and respectively. There were statistically obvious differences between the 3 groups (P 0.05). Death occurred in 1 canine(high dose group) within 24 hours after thrombolysis with hemorrhagic lesion in parietal lobe of brain. No other severe complications ocurred. Conclusions: (1) Intraarterial thrombolysis with r-Sak within 5 hours after onset of thrombosis is effective and feasible. Intraarterial r-Sak shows strong thrombolytic effect for white thrombus including a few platelets. There is relative high rate of recanalization with no less than 10 000U/kg of r-Sak but accompanied with high risk of

  19. Radiographic, densitometric, and biomechanical effects of recombinant canine somatotropin in an unstable ostectomy gap model of bone healing in dogs

    International Nuclear Information System (INIS)

    Millis, D.L.; Wilkens, B.E.; Daniel, G.B.; Hubner, K.; Mathews, A.; Buonomo, F.C.; Patell, K.R.; Weigel, J.P.

    1998-01-01

    Objective: To determine the effect of recombinant canine somatotropin (STH) on radiographic, densitometric, and biomechanical aspects of bone healing using an unstable ostectomy gap model. Study Design: After an ostectomy of the midshaft radius, bone healing was evaluated over an 8-week period in control dogs (n = 4) and dogs receiving recombinant canine STH (n = 4). Animals Or Sample Population: Eight sexually intact female Beagle dogs, 4 to 5 years old. Methods: Bone healing was evaluated by qualitative and quantitative evaluation of serial radiographs every 2 weeks. Terminal dual-energy x-ray absorptiometry and three-point bending biomechanical testing were also performed. Results: Dogs receiving STH had more advanced radiographic healing of ostectomy sites. Bone area, bone mineral content, and bone density were two to five times greater at the ostectomy sites of treated dogs. Ultimate load at failure and stiffness were three and five times greater in dogs receiving STH. Conclusions: Using the ostectomy gap model, recombinant canine STH enhanced the radiographic, densitometric, and biomechanical aspects of bone healing in dogs. Clinical Relevance: Dogs at risk for delayed healing of fractures may benefit from treatment with recombinant canine STH

  20. The mechanical consequence of failure of ossified union in attempted posterior spinal fusion. A canine model.

    Science.gov (United States)

    Stonecipher, T K; Vanderby, R; Sciammarella, C A; Lei, S S; Fisk, J R

    1983-01-01

    The mechanical behavior of pseudarthrosis in posterior spinal fusion was investigated. A canine model was developed in which an incompletely ossified posterior fusion mass was consistently produced. The spines were excised, and the motion segments were mechanically tested using a specially developed loading apparatus. Tests were performed to evaluate stiffness of the segments to loading with compression, torsion, and anterioposterior and lateral bending shear stiffness. Changes in other modes of loading were less consistent. The motion characteristics of the pseudarthrosis could not be predicted from the extent of the osseous defect noted on roentgenograms. These findings correlate clinically with the progression of curvature seen with pseudarthrosis in scoliosis surgery and the unpredictable results of pseudarthrosis in posterior fusion performed in treatment of degenerative disc disease.

  1. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-10-11

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

  2. Effects of Recombinant Human Bone Morphogenetic Protein-2 on Vertical Bone Augmentation in a Canine Model.

    Science.gov (United States)

    Hsu, Yung-Ting; Al-Hezaimi, Khalid; Galindo-Moreno, Pablo; O'Valle, Francisco; Al-Rasheed, Abdulaziz; Wang, Hom-Lay

    2017-09-01

    Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)-2, under space-making titanium mesh in a canine model. Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP-2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4-month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro-CT) assessment and histologic analysis. Membrane exposure was found on five of 11 (45.5%) rhBMP-2-treated sites, whereas it was found on nine of 11 (81.8%) non-rhBMP-2-treated sites. Within 4 months of healing, rhBMP-2-treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P 0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP-2 sites. With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP-2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non-rhBMP-2 sites.

  3. Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

    OpenAIRE

    Rütgen, Barbara C.; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stabilit...

  4. Comparative strain analysis of Anaplasma phagocytophilum infection and clinical outcomes in a canine model of granulocytic anaplasmosis.

    Science.gov (United States)

    Scorpio, Diana G; Dumler, J Stephen; Barat, Nicole C; Cook, Judith A; Barat, Christopher E; Stillman, Brett A; DeBisceglie, Kristen C; Beall, Melissa J; Chandrashekar, Ramaswamy

    2011-03-01

    A pilot study was conducted to determine whether existing human or canine strains of Anaplasma phagocytophilum would reproduce clinical disease in experimentally inoculated dogs similar to dogs with naturally acquired granulocytic anaplasmosis. Six hounds were inoculated intravenously with one human and two canine strains of A. phagocytophilum that were propagated in vitro in HL-60 cells or in infected autologous neutrophils. Infected dogs were monitored for lethargy, anorexia, petechiae, lymphadenopathy, and fever. Dogs were assessed for complete blood count (CBC), serum chemistry, and serology (IFA and SNAP® 4Dx®); for A. phagocytophilum blood load by quantitative polymerase chain reaction; and for cytokine production. Prominent clinical signs were generalized lymphadenopathy and scleral injection; only one dog developed fever lasting 4 days. Notable laboratory alterations included sustained leukopenia and thrombocytopenia in all dogs. A. phagocytophilum morulae were noted in blood between days 10 and 11, although all dogs retained A. phagocytophilum DNA in blood through day 60. All dogs seroconverted by days 10-15 by IFA, and by days 17-30 by SNAP 4Dx; cytokine analyses revealed 10-fold increases in interleukin-2 and interleukin-18 in the neutrophil-propagated 98E4 strain-infected dog. All A. phagocytophilum strains produced infection, although canine 98E4 strain reproduced clinical signs, hematologic changes, and inflammatory cytokine elevations most consistent with granulocytic anaplasmosis when recognized clinically. Therefore, this strain should be considered for use in future studies of A. phagocytophilum canine infection models.

  5. Endovascular treatment of wide-necked aneurysms using stents combined with electrolytic detachable coils in a canine model

    International Nuclear Information System (INIS)

    Liu Jianmin; Zhang Xin; Zhou Xiaoping; Hong Bo; Xu Yi; Huang Qinghai; Zhang Long; She Jiagui; Zhao Rui

    2004-01-01

    Objective: To assess hemodynamics and histology of the aneurysms by treating experimental wide-necked aneurysms endovascularly with a combination of stents and electrolytic detachable coils. Methods: An experimental model was surgically constructed in the necks of six canines for simulating intracranial wide-necked aneurysms. Balloon-expandable metal stents were positioned across the aneurysms in bilateral carotid arteries of six canines with additional intraaneurysmal placement of detachable microcoils in only unilateral carotid artery of each canine. Sonography and angiography were performed in different stages and histologic examinations were achieved finally. Results: Stent placement was successful in all six canines. Aneurysms treated with only stents placement showed no significant thrombus formation with slow growing of neointima over the neck of the aneurysm. Thrombosis occurred in the aneurysms treated with stents and coils in a short time and neointima covered the neck of the aneurysms completely. Conclusions: Endovascular treatment of wide-necked aneurysms using stents combined with electrolytic detachable coils may prevent re-rupture of the aneurysms and promote neointima formation over the neck of the aneurysms. (authors)

  6. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    International Nuclear Information System (INIS)

    Kodama, Atsushi; Yanai, Tokuma; Sakai, Hiroki; Matsuura, Satoko; Murakami, Mami; Murai, Atsuko; Mori, Takashi; Maruo, Kouji; Kimura, Tohru; Masegi, Toshiaki

    2009-01-01

    Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

  7. Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes.

    Directory of Open Access Journals (Sweden)

    Viorica Ionut

    Full Text Available Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes.We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines.After 10 weeks of high-fat diet (HFD, adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg. After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7 or placebo (n = 7 for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG, the oral glucose tolerance test (OGTT, insulinogenic index and the graded-hyperglycemic clamp (clamp insulinogenic index. Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro.OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5% (P = 0.011. IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9% (P = 0.002. AIRG decreased by 54.0% (IQR, 40.7% (P = 0.010, leading to mild fasting hyperglycemia (P = 0.039. Exenatide, compared with placebo, decreased body weight (P<0.001 without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040 and clamp-based insulinogenic indexes (P = 0.016, improved insulin secretion in vitro (P = 0.041, but had no noticeable effect on insulin sensitivity (P = 0.405.In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes.

  8. Evaluation of type II thyroplasty on phonatory physiology in an excised canine larynx model

    Science.gov (United States)

    Devine, Erin E.; Hoffman, Matthew R.; McCulloch, Timothy M.; Jiang, Jack J.

    2016-01-01

    Objective Type II thyroplasty is an alternative treatment for spasmodic dysphonia, addressing hyperadduction by incising and lateralizing the thyroid cartilage. We quantified the effect of lateralization width on phonatory physiology using excised canine larynges. Methods Normal closure, hyperadduction, and type II thyroplasty (lateralized up to 5mm at 1mm increments with hyperadducted arytenoids) were simulated in excised larynges (N=7). Aerodynamic, acoustic, and videokymographic data were recorded at three subglottal pressures relative to phonation threshold pressure (PTP). One-way repeated measures ANOVA assessed effect of condition on aerodynamic parameters. Random intercepts linear mixed effects models assessed effects of condition and subglottal pressure on acoustic and videokymographic parameters. Results PTP differed across conditions (p<0.001). Condition affected percent shimmer (p<0.005) but not percent jitter. Both pressure (p<0.03) and condition (p<0.001) affected fundamental frequency. Pressure affected vibratory amplitude (p<0.05) and intra-fold phase difference (p<0.05). Condition affected phase difference between the vocal folds (p<0.001). Conclusions Hyperadduction increased PTP and worsened perturbation compared to normal, with near normal physiology restored with 1mm lateralization. Further lateralization deteriorated voice quality and increased PTP. Acoustic and videokymographic results indicate that normal physiologic relationships between subglottal pressure and vibration are preserved at optimal lateralization width, but then degrade with further lateralization. The 1mm optimal width observed here is due to the small canine larynx size. Future human trials would likely demonstrate a greater optimal width, with patient-specific value potentially determined based on larynx size and symptom severity. PMID:27223665

  9. Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

    Science.gov (United States)

    Chang, Sung Soo; Yokomise, Hiroyasu; Matsuura, Natsumi; Gotoh, Masashi; Tabata, Yasuhiko

    2014-08-01

    The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

  10. A cell kinetic model of granulopoiesis under radiation exposure: Extension from rodents to canines and humans

    International Nuclear Information System (INIS)

    Hu, S.; Cucinotta, F. A.

    2011-01-01

    As significant ionising radiation exposure will occur during prolonged space travel in future, it is essential to understand their adverse effects on the radiosensitive organ systems that are important for immediate survival of humans, e.g. the haematopoietic system. In this paper, a bio-mathematical model of granulopoiesis is used to analyse the granulocyte changes seen in the blood of mammalians under acute and continuous radiation exposure. This is one of a set of haematopoietic models that have been successfully utilised to simulate and interpret the experimental data of acute and chronic radiation on rodents. Extension to canine and human systems indicates that the results of the model are consistent with the cumulative experimental and empirical data from various sources, implying the potential to integrate them into one united model system to monitor the haematopoietic response of various species under irradiation. The suppression of granulocytes' level of a space traveller under chronic stress of low-dose irradiation as well as the granulopoietic response when encountering a historically large solar particle event is also discussed. (authors)

  11. Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.

    Science.gov (United States)

    Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre; Katz, Nathan; Zhu, Yanqing; Lin, Gloria; Choa, Ruth; Bagel, Jessica; O'Donnell, Patricia; Fitzgerald, Caitlin A; Langan, Therese; Wang, Ping; Casal, Margret L; Haskins, Mark E; Wilson, James M

    2016-09-01

    High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A Canine Arthroscopic Anterior Cruciate Ligament Reconstruction Model for Study of Synthetic Augmentation of Tendon Allografts.

    Science.gov (United States)

    Cook, James L; Smith, Pat; Stannard, James P; Pfeiffer, Ferris; Kuroki, Keiichi; Bozynski, Chantelle C; Cook, Cristi

    2017-09-01

    Novel graft types, fixation methods, and means for augmenting anterior cruciate ligament (ACL) reconstructions require preclinical validation prior to safe and effective clinical application. The objective of this study was to describe and validate a translational canine model for all-inside arthroscopic complete ACL reconstruction using a quadriceps tendon allograft with internal brace (QTIB). With institutional approval, adult research hounds underwent complete transection of the native ACL followed by all-inside ACL reconstruction using the novel QTIB construct with suspensory fixation ( n  = 10). Contralateral knees were used as nonoperated controls ( n  = 10). Dogs were assessed over a 6-month period using functional, diagnostic imaging, gross, biomechanical, and histologic outcome measures required for preclinical animal models. Study results suggest that the novel QTIB construct used for complete ACL reconstruction can provide sustained knee stability and function without the development of premature osteoarthritis in a rigorous and valid preclinical model. The unique configuration of the QTIB construct-the combination of a tendon allograft with a synthetic suture tape internal brace-allowed for an effective biologic-synthetic load-sharing ACL construct. It prevented early failure, allowed for direct, four-zone graft-to-bone healing, and functional graft remodeling while avoiding problems noted with use of all-synthetic grafts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Canine periodontitis: the dog as an important model for periodontal studies.

    Science.gov (United States)

    Albuquerque, Carlos; Morinha, Francisco; Requicha, João; Martins, Teresa; Dias, Isabel; Guedes-Pinto, Henrique; Bastos, Estela; Viegas, Carlos

    2012-03-01

    Periodontal disease (PD) refers to a group of inflammatory diseases caused by bacterial plaque in the periodontium and ranges from an early stage (gingivitis) to an advanced stage (periodontitis). It is a multifactorial disease that results from the interaction of the host defence mechanisms with the plaque microorganisms. Early detection, diagnosis and treatment are essential in the control of this disease. PD has an enormous impact on human and veterinary medicine due to its high prevalence. The most common animal PD models use dogs and non-human primates, although other animals (rats, mice, hamsters, rabbits, miniature pigs, ferrets, and sheep) have also been employed. Dog models have contributed significantly to the current understanding of periodontology. The most important clinical aspects of canine PD are considered in this review and the various animal models are examined with an emphasis on the role of the dog as the most useful approach for understanding human PD and in the development of new therapeutic and preventive measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    OpenAIRE

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie

    2010-01-01

    This study by the groups of Drs. Barry Byrne and Cathryn Mah at the University of Florida examines the safety and efficacy of AAV-mediated gene delivery in a canine model of glycogen storage disease type Ia (GSDIa). The authors find that intraportal delivery of AAV8 encoding glucose-6-phosphatase-α (G6Pase) followed 20 weeks later by intraportal administration of AAV1 encoding G6Pase led to significant correction of the GSDIa phenotype.

  15. Application of a canine 238Pu dosimetry model to human bioassay data

    Energy Technology Data Exchange (ETDEWEB)

    Hickman, Jr., A. W. [Florida Univ., Gainesville, FL (United States)

    1991-08-01

    Associated with the use of 2238Pu in thermoelectric power sources for space probes and power supplies for cardiac devices is the potential for human exposure to 238Pu, primarily by inhalation. In the event of human internal exposure, a means is needed for assessing the level of intake and calculating radiation doses. Several bioassay/dosimetry models have been developed for 239Pu. However, results from studies with laboratory animals have indicated that the biokinetics, and therefore the descriptive models, of 238Pu are significantly different from those for 239Pu. A canine model accounting for these differences has been applied in this work to urinary excretion data from seven humans occupationally exposed to low levels of an insoluble 238Pu compound. The modified model provides a good description of the urinary excretion kinetics observed in the exposed humans. The modified model was also used to provide estimates of the initial intakes of 238Pu for the seven individuals; these estimates ranged from 4.5 nCi (170 Bq) to 87 nCi (3200 Bq). Autopsy data on the amount and distribution of 238Pu retained in the organs may be used in the future to validate or refute both these estimates and the assumptions used to formulate the human model. Modification of the human model to simulate an injection exposure to 239Pu gave patterns of retention in the organs and urinary excretion comparable to those seen previously in humans; further modification of the model using fecal data (unavailable for the subjects of this study) is indicated.

  16. DSA-guided embolization in establishing different canine spinal cord ischemia models and relevant diffusion-weighted imaging study

    International Nuclear Information System (INIS)

    Zhang Jingsong; Sun Lijun; Huan Yi; He Hongde; Zhang Xuexin; Zhao Haitao; Zhang Jing; Zhang Xijing

    2006-01-01

    Objective: To evaluate DSA-guided embolization in establishing different spinal cord ischemia models of canine and relevant diffusion-weighted imaging (DWI) application. Methods: Nine canines were randomly divided into three groups with different matching of lipiodol and diatrizoate meglumine which were injected into bilateral intercostal arteries at 9-11 level guided by DSA monitor. Then observe the changes of motor function and pathologic findings, especially perform routine MRI and DWI by a 1.5 T MR system. Results: Except one case, 8 embolization models were established successfully. Among three groups, slight-group got slight injury and muscle power was about 3-5 grade and range of injury was about two vertebra distance; medium-group presented obvious paraplegia and muscle power was 0-1 grade and range of injury was between 3-4 vertebra distance; severe-group showed greater severity and larger range of injury. All lesions presented high signals at routine MRI and DWI. Conclusion: Using different matching of lipiodol and diatrizoate meglumine can establish different spinal cord ischemia models of canine by DSA- guided embolization and DWI can be performed successfully by 1.5 T MR system, which may be a good method for advanced study of spinal cord ischemia. (authors)

  17. Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase.

    Science.gov (United States)

    Jeong, Yeon Woo; Lee, Geun-Shik; Kim, Joung Joo; Park, Sun Woo; Ko, Kyeong Hee; Kang, Mina; Kim, Yu Kyung; Jung, Eui-Man; Hyun, Sang Hwan; Shin, Taeyoung; Jeung, Eui-Bae; Hwang, Woo Suk

    2012-08-01

    Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expressing the phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning efficiency associated with adult or fetal (cloned or natural mating) fibroblasts as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy and cloning rates. The fusion rates were significantly high for fibroblasts from cloned fetuses, but the pregnancy and cloning rates were relatively high for cells from normal fetuses. Based on these data, fetal fibroblasts were selected as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK gene and dual selection marker genes controlled by the PEPCK promoter. The transgenic cells were introduced into oocytes and transferred into five recipient dogs, resulting in two pregnancies. Finally, three puppies were born and confirmed by microsatellite analysis to be genetically identical to the donor. One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This canine disease model may be useful for studying the pathogenesis and/or therapeutic targets of type 2 diabetes mellitus.

  18. Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model

    Directory of Open Access Journals (Sweden)

    Nasim Akhtar

    2004-03-01

    Full Text Available We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF receptors 1 and 2, CD31, CD146, and αvβ3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.

  19. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    International Nuclear Information System (INIS)

    Fork, Melani AM; Bullerdiek, Jörn; Nolte, Ingo; Escobar, Hugo Murua; Soller, Jan T; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J

    2008-01-01

    Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-Prkdc Scid /J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies

  20. Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models

    Directory of Open Access Journals (Sweden)

    Michael D. Poscente

    2014-01-01

    Full Text Available Transcutaneous intraluminal impedance measurement (TIIM is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham, two force transducers (FT were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs were calculated and Pearson correlation coefficients (PCCs between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans.

  1. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    Science.gov (United States)

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  2. Evaluation of Osseous Integration of PVD-Silver-Coated Hip Prostheses in a Canine Model

    Directory of Open Access Journals (Sweden)

    Gregor Hauschild

    2015-01-01

    Full Text Available Infection associated with biomaterials used for orthopedic prostheses remains a serious complication in orthopedics, especially tumor surgery. Silver-coating of orthopedic (megaprostheses proved its efficiency in reducing infections but has been limited to surface areas exposed to soft tissues due to concerns of silver inhibiting osseous integration of cementless stems. To close this gap in the bactericidal capacity of silver-coated orthopedic prostheses extension of the silver-coating on surface areas intended for osseous integration seems to be inevitable. Our study reports about a PVD- (physical-vapor-deposition- silver-coated cementless stem in a canine model for the first time and showed osseous integration of a silver-coated titanium surface in vivo. Radiological, histological, and biomechanical analysis revealed a stable osseous integration of four of nine stems implanted. Silver trace elemental concentrations in serum did not exceed 1.82 parts per billion (ppb and can be considered as nontoxic. Changes in liver and kidney functions associated with the silver-coating could be excluded by blood chemistry analysis. This was in accordance with very limited metal displacement from coated surfaces observed by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS 12 months after implantation. In conclusion our results represent a step towards complete bactericidal silver-coating of orthopedic prostheses.

  3. A novel device for the occlusion of left atrial appendage: an experimental study in canine models

    International Nuclear Information System (INIS)

    Yang Zhihong; Qin Yongwen; Wu Hong; Hu Jianqiang; Wang Shengqiang; Ding Zhongru; Liu Zongjun

    2011-01-01

    Objective: To evaluate the feasibility, safety and biocompatibility of a novel device designed by the authors for the occlusion of left atrial appendage (LAA) in canine models. Methods: The occlusion of LAA was performed in 20 experimental dogs by using a novel LAA occluder, which was delivered to the LAA through a transseptal catheter. During the period of 2 weeks to 6 months after the procedure, the dogs were kept under observation for the device healing, migration, perforation and the formation of thrombus. Both scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to examine the endothelial growth on the surface of the occluder and the structure of the endothelial cells. Results: Of the total 20 dogs, the novel device was successfully implanted in 14. The LAA was occluded completely in 13 dogs. No mobile thrombi caused by the implantation procedure were observed. Endothelialization of the atrium-facing surface was observed at one month after the procedure, and the surface was completely covered with endothelial cells at 3 months after the treatment, which was confirmed by gross, histological and SEM examinations. TEM examination showed that the structure of endothelial cells, the mitochondrion and sarcomere of atrial cardiocyte were all normal. Gross and light microscopic examination of the kidney, lung spleen and liver showed that there was no evidence of embolism or infarction. Conclusion: The novel device is safe and feasible for the occlusion of the LAA in experimental dogs. Further study is needed to observe its long-term safety. (authors)

  4. Metabolism of model organic pollutants in canine respiratory tract mucosa slices

    International Nuclear Information System (INIS)

    Thornton-Manning, J.R.; Gerde, P.; Chen, S.T.; Dahl, A.R.

    1994-01-01

    The high incidence of human bronchial tumors has been correlated with the high fractional deposition of inhaled particles in the bronchi. Polycyclic aromatic hydrocarbons (PAHs) are frequently bound to airborne particles due to their low vapor pressures. It is thought that tumorigenicity may result from the release and subsequent bioactivation of these particle-associated organic compounds in the respiratory tract. Previous studies at ITRI examined the clearance of organic toxicants from various regions of the canine respiratory tract. Their results indicated that, while clearance of a highly lipophilic PAH such as benzo(a)pyrene (BaP) from the thin alveolar epithelium took only a few minutes, clearance through the thicker epithelium of the conducting airways took hours. Slower, diffusion-limited clearance results in higher concentrations of lipophilic compounds in the epithelium of the bronchi. Hence, the ability of these tissues to metabolize organic compounds to water-soluble metabolites or reactive intermediates may be extremely important in their clearance from the respiratory tract and the potential susceptibility of this region of the respiratory tract to cancer. The purpose of the present study was to evaluate the ability of bronchial mucosa to metabolize a model organic pulmonary carcinogen, BaP, to reactive and nonreactive metabolites and to evaluate the diffusion of the parent compound and metabolites through the bronchial mucosa

  5. Evaluation of osseous integration of PVD-silver-coated hip prostheses in a canine model.

    Science.gov (United States)

    Hauschild, Gregor; Hardes, Jendrik; Gosheger, Georg; Stoeppeler, Sandra; Ahrens, Helmut; Blaske, Franziska; Wehe, Christoph; Karst, Uwe; Höll, Steffen

    2015-01-01

    Infection associated with biomaterials used for orthopedic prostheses remains a serious complication in orthopedics, especially tumor surgery. Silver-coating of orthopedic (mega)prostheses proved its efficiency in reducing infections but has been limited to surface areas exposed to soft tissues due to concerns of silver inhibiting osseous integration of cementless stems. To close this gap in the bactericidal capacity of silver-coated orthopedic prostheses extension of the silver-coating on surface areas intended for osseous integration seems to be inevitable. Our study reports about a PVD- (physical-vapor-deposition-) silver-coated cementless stem in a canine model for the first time and showed osseous integration of a silver-coated titanium surface in vivo. Radiological, histological, and biomechanical analysis revealed a stable osseous integration of four of nine stems implanted. Silver trace elemental concentrations in serum did not exceed 1.82 parts per billion (ppb) and can be considered as nontoxic. Changes in liver and kidney functions associated with the silver-coating could be excluded by blood chemistry analysis. This was in accordance with very limited metal displacement from coated surfaces observed by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) 12 months after implantation. In conclusion our results represent a step towards complete bactericidal silver-coating of orthopedic prostheses.

  6. A computerized MRI biomarker quantification scheme for a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Wang, Jiahui; Fan, Zheng; Vandenborne, Krista; Walter, Glenn; Shiloh-Malawsky, Yael; An, Hongyu; Kornegay, Joe N; Styner, Martin A

    2013-09-01

    Golden retriever muscular dystrophy (GRMD) is a widely used canine model of Duchenne muscular dystrophy (DMD). Recent studies have shown that magnetic resonance imaging (MRI) can be used to non-invasively detect consistent changes in both DMD and GRMD. In this paper, we propose a semiautomated system to quantify MRI biomarkers of GRMD. Our system was applied to a database of 45 MRI scans from 8 normal and 10 GRMD dogs in a longitudinal natural history study. We first segmented six proximal pelvic limb muscles using a semiautomated full muscle segmentation method. We then performed preprocessing, including intensity inhomogeneity correction, spatial registration of different image sequences, intensity calibration of T2-weighted and T2-weighted fat-suppressed images, and calculation of MRI biomarker maps. Finally, for each of the segmented muscles, we automatically measured MRI biomarkers of muscle volume, intensity statistics over MRI biomarker maps, and statistical image texture features. The muscle volume and the mean intensities in T2 value, fat, and water maps showed group differences between normal and GRMD dogs. For the statistical texture biomarkers, both the histogram and run-length matrix features showed obvious group differences between normal and GRMD dogs. The full muscle segmentation showed significantly less error and variability in the proposed biomarkers when compared to the standard, limited muscle range segmentation. The experimental results demonstrated that this quantification tool could reliably quantify MRI biomarkers in GRMD dogs, suggesting that it would also be useful for quantifying disease progression and measuring therapeutic effect in DMD patients.

  7. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  8. An evaluation of the histological effects of intra-articular methadone in the canine model.

    Science.gov (United States)

    Jones, Timothy A; Hand, Walter R; Ports, Michael D; Unger, Daniel V; Herbert, Daniel; Pellegrini, Joseph E

    2003-02-01

    Methadone hydrochloride is an opiate that has pharmacodynamic and pharmacokinetic properties that suggest it may provide longer analgesia than morphine when administered via the intra-articular route. However, no studies to date have been conducted examining the effects of intra-articular methadone hydrochloride on local tissues. Therefore, the purpose of this study was to determine the histopathologic effects of intra-articular methadone hydrochloride on local tissues in the canine knee. Nine canines, 1 to 4 years old, weighing between 20 kg and 23 kg were used. All canines had their knees randomized to receive either bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 5 mg methadone hydrochloride (0.5 mL) for the study knee, or bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 0.5 mL normal saline for the control knee. Serum methadone hydrochloride levels were obtained on all canines at 6 and 24 hours. Canines were randomly assigned to 1 of 3 groups to be euthanized at either 24 hours, 14 days, or 28 days. Following euthanization and necropsy, synovial fluid levels and tissue samples were obtained and examined for histopathologic changes. Synovial fluid samples noted a few white blood cells at 24 hours and none at 14 and 28 days. Tissue samples showed no histopathologic changes, and serum concentration levels of methadone hydrochloride were negligible.

  9. Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model.

    Science.gov (United States)

    Crisp, Matthew J; Beckett, Jeffrey; Coates, Joan R; Miller, Timothy M

    2013-10-01

    Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. We show that a detergent-insoluble species of mutant SOD1 is present in spinal cords of affected dogs that increases with disease progression. Our in vitro results indicate that both canine SOD1 mutants form enzymatically active dimers, arguing against a loss of function in affected homozygous animals. Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Image-Based Macro-Micro Finite Element Models of a Canine Femur with Implant Design Implications

    Science.gov (United States)

    Ghosh, Somnath; Krishnan, Ganapathi; Dyce, Jonathan

    2006-06-01

    In this paper, a comprehensive model of a bone-cement-implant assembly is developed for a canine cemented femoral prosthesis system. Various steps in this development entail profiling the canine femur contours by computed tomography (CT) scanning, computer aided design (CAD) reconstruction of the canine femur from CT images, CAD modeling of the implant from implant blue prints and CAD modeling of the interface cement. Finite element analysis of the macroscopic assembly is conducted for stress analysis in individual components of the system, accounting for variation in density and material properties in the porous bone material. A sensitivity analysis is conducted with the macroscopic model to investigate the effect of implant design variables on the stress distribution in the assembly. Subsequently, rigorous microstructural analysis of the bone incorporating the morphological intricacies is conducted. Various steps in this development include acquisition of the bone microstructural data from histological serial sectioning, stacking of sections to obtain 3D renderings of void distributions, microstructural characterization and determination of properties and, finally, microstructural stress analysis using a 3D Voronoi cell finite element method. Generation of the simulated microstructure and analysis by the 3D Voronoi cell finite element model provides a new way of modeling complex microstructures and correlating to morphological characteristics. An inverse calculation of the material parameters of bone by combining macroscopic experiments with microstructural characterization and analysis provides a new approach to evaluating properties without having to do experiments at this scale. Finally, the microstructural stresses in the femur are computed using the 3D VCFEM to study the stress distribution at the scale of the bone porosity. Significant difference is observed between the macroscopic stresses and the peak microscopic stresses at different locations.

  11. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    Directory of Open Access Journals (Sweden)

    Winkler Susanne

    2008-08-01

    Full Text Available Abstract Background Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. Methods For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. Results The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Conclusion Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies.

  12. Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model.

    Directory of Open Access Journals (Sweden)

    Chufeng Liu

    Full Text Available The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time.Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression.The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63±0.10 mm and the average anchorage losses were 1.25±0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs.This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications.It may become a novel method to shorten the clinical orthodontic treatment time in the future.

  13. Transcutaneous glomerular filtration rate measurement in a canine animal model of chronic kidney disease.

    Science.gov (United States)

    Mondritzki, Thomas; Steinbach, Sarah M L; Boehme, Philip; Hoffmann, Jessica; Kullmann, Maximilian; Schock-Kusch, Daniel; Vogel, Julia; Kolkhof, Peter; Sandner, Peter; Bischoff, Erwin; Hüser, Jörg; Dinh, Wilfried; Truebel, Hubert

    Quantitative assessment of renal function by measurement of glomerular filtration rate (GFR) is an important part of safety and efficacy evaluation in preclinical drug development. Existing methods are often time consuming, imprecise and associated with animal burden. Here we describe the comparison between GFR determinations with sinistrin (PS-GFR) and fluorescence-labelled sinistrin-application and its transcutaneous detection (TD-GFR) in a large animal model of chronic kidney disease (CKD). TD-GFR measurements compared to a standard method using i.v. sinistrin were performed in a canine model. Animals were treated with one-sided renal wrapping (RW) followed by renal artery occlusion (RO). Biomarker and remote hemodynamic measurements were performed. Plasma sinistrin in comparison to transcutaneous derived GFR data were determined during healthy conditions, after RW and RW+RO. RW alone did not led to any significant changes in renal function, neither with PS-GFR nor TD-GFR. Additional RO showed a rise in blood pressure (+68.0mmHg), plasma urea (+28.8mmol/l), creatinine (+224,4μmol/l) and symmetric dimethylarginine (SDMA™; +12.6μg/dl). Plasma sinistrin derived data confirmed the expected drop (-44.7%, p<0.0001) in GFR. The calculated transcutaneous determined Fluorescein Isothiocyanate (FITC)-sinistrin GFR showed no differences to plasma sinistrin GFR at all times. Both methods were equaly sensitive to diagnose renal dysfunction in the affected animals. Renal function assessment using TD-GFR is a valid method to improve preclinical drug discovery and development. Furthermore, TD-GFR method offers advantages in terms of reduced need for blood sampling and thus decreasing animal burden compared to standard procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. MRI-based quantification of Duchenne muscular dystrophy in a canine model

    Science.gov (United States)

    Wang, Jiahui; Fan, Zheng; Kornegay, Joe N.; Styner, Martin A.

    2011-03-01

    Duchenne muscular dystrophy (DMD) is a progressive and fatal X-linked disease caused by mutations in the DMD gene. Magnetic resonance imaging (MRI) has shown potential to provide non-invasive and objective biomarkers for monitoring disease progression and therapeutic effect in DMD. In this paper, we propose a semi-automated scheme to quantify MRI features of golden retriever muscular dystrophy (GRMD), a canine model of DMD. Our method was applied to a natural history data set and a hydrodynamic limb perfusion data set. The scheme is composed of three modules: pre-processing, muscle segmentation, and feature analysis. The pre-processing module includes: calculation of T2 maps, spatial registration of T2 weighted (T2WI) images, T2 weighted fat suppressed (T2FS) images, and T2 maps, and intensity calibration of T2WI and T2FS images. We then manually segment six pelvic limb muscles. For each of the segmented muscles, we finally automatically measure volume and intensity statistics of the T2FS images and T2 maps. For the natural history study, our results showed that four of six muscles in affected dogs had smaller volumes and all had higher mean intensities in T2 maps as compared to normal dogs. For the perfusion study, the muscle volumes and mean intensities in T2FS were increased in the post-perfusion MRI scans as compared to pre-perfusion MRI scans, as predicted. We conclude that our scheme successfully performs quantitative analysis of muscle MRI features of GRMD.

  15. Determination of selenium status using the nail biologic monitor in a canine model

    International Nuclear Information System (INIS)

    Steven Morris, J.; Spate, V.L.; Ruth Ann Ngwenyama; Waters, D.J.

    2012-01-01

    Toenails and fingernails are routinely used to estimate selenium status in epidemiological studies; however, literature validating nail selenium concentration as a surrogate for critical organs is limited. In this study diets of intact male dogs were selenium supplemented at two physiological levels (3 and 6 μg/kg/day) in two different forms, selenomethionine and selenium-enriched bioformed yeast. The selenium-adequate basal diet consumed by the treatment and control groups during the 4-week run-in period and throughout the trial contained 0.3 ppm selenium. After 7 months the dogs in the two treatment groups and the control group were euthanized. Representative tissue samples from prostate, brain, liver, heart and skeletal muscle were collected, rinsed and frozen. Toenail clippings from multiple toes were also collected. Selenium was determined by neutron activation analysis using Se77m (half life = 17.4 s) at the University of Missouri Research Reactor Center. NIST SRM 1577, Bovine Liver was analyzed as a quality control. The analysts were blinded to control and treatment group assignments. As expected, tissue selenium levels increased proportionally with supplementation. A slightly greater increase in tissue selenium was observed for the purified selenomethionine compared to the bioformed yeast; however this trend was significant only for brain tissue. Toenail selenium concentrations and tissue selenium were highly correlated (p < 0.003) with Pearson coefficients of 0.759 (skeletal muscle), 0.745 (heart), 0.729 (brain), 0.723 (prostate), and 0.632 (liver). The toenail biologic monitor accurately assesses selenium status in skeletal muscle, heart, brain, prostate, and liver in the canine model. (author)

  16. Study on the related factors influencing the formation of intra-aneurysmal thrombosis in the established side-wall aneurysmal model in canine

    International Nuclear Information System (INIS)

    Zhou Bing; Li Minghua; Wang Jianbo; Zhu Yueqi; Yuan Jianhua; Yu Wenqiang

    2011-01-01

    Objective: To analyze the related factors influencing the formation of intra-aneurysmal thrombosis (IAT) in the established side-wall aneurysmal model in canine, and to discuss the measures to prevent the occurrence of IAT. Methods: Twenty canines were randomly divided into 4 groups for building side-wall aneurysmal model: group A, vertical aneurysm without use of postoperative anticoagulation medication; group B, vertical aneurysm with use of postoperative anticoagulation medication; group C, oblique aneurysm without use of postoperative anticoagulation medication; and group D, oblique aneurysm with use of postoperative anticoagulation medication. Angiography was performed to evaluate the IAT. The potential related factors influencing the formation of IAT, including sex, age, operative time, aneurysmal morphology, postoperative anticoagulation medication and cervical hematoma, were statistically analysed with emphasis on aneurysmal morphology and the use of postoperative anticoagulation medication. The statistical software SPSS 12.0 was employed. Results: A total of 40 aneurysms were successfully established in 20 canines. Cervical hematoma occurred in 7 canines and IAT developed in 8 aneurysms. The univariate analysis showed that the formation of IAT was significantly influenced by the aneurysmal morphology and cervical hematoma. Surprisingly, the formation of IAT bore no relation to the postoperative anticoagulation, whether the medication was employed or not, which was further confirmed by stratified analysis. Conclusion: To establish oblique aneurysm and to reduce the occurrence of cervical hematoma can effectively decrease the incidence of IAT in established side-wall aneurysmal model in canine. The postoperative anticoagulation medication can not decrease the incidence of IAT. (authors)

  17. Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2018-01-01

    What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1

  18. A novel canine model of portal vein stenosis plus thioacetamide administration-induced cirrhotic portal hypertension with hypersplenism.

    Science.gov (United States)

    Lin, Dexin; Wu, Xianbin; Ji, Xiaoke; Zhang, Qiyu; Lin, YuanWei; Chen, WeiJian; Jin, Wangxun; Deng, Liming; Chen, Yunzhi; Chen, Bicheng; Li, Jianmin

    2012-01-01

    Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.

  19. The establishment of transmissible venereal tumor lung cancer model in canine and the observation of its biological characteristics

    International Nuclear Information System (INIS)

    Sun Zhichao; Dong Weihua; Xiao Xiangsheng; Zhu Ruimin; Chen mofan; Wang Zhi

    2010-01-01

    Objective: To establish an allogeneic transplanted lung cancer model in canine by percutaneously injecting canine transmissible venereal tumor (CTVT) cell suspension and to observe its biological characteristics. Methods: Under CT guidance fresh CTVT cell suspension was inoculated into the middle or posterior lobe of lungs through percutaneous puncturing needle in 12 beagle dogs. Cyclosporin was administrated orally to obtain immunosuppression. Tumor growth and metastasis were judged by chest CT scanning at regular intervals (every 1-2 weeks). The daily mental and physical condition of the dogs was observed. Autopsy and pathological examination were performed when the animals died naturally or at the tenth week after the procedure when the animals were sacrificed. Results: A total of 15 sites were inoculated in 12 dogs. The formation of tumor was observed in 2 dogs at the fifth week and in 9 dogs at the sixth week. Ten weeks after the inoculation the formation of tumor was detected in 10 inoculated points in 9 dogs, the inoculation success rate was 66.67%. The mean largest diameter of the tumor at 6, 8 and 10 weeks after the inoculation was (1.059 ± 0.113)cm, (1.827 ± 0.084)cm and (2.189 ± 0.153)cm, respectively. The largest diameter of the tumor nodule was 3.5 cm. Moderate to severe pleural effusion and mediastinal lymph nodes metastasis were found in all the dogs that showed the formation of the tumor. Conclusion: Percutaneous CTVT cell suspension injection can establish an allogeneic canine lung cancer model, which is helpful for the experimental studies related to lung cancer. (authors)

  20. Dual AAV Gene Therapy for Duchenne Muscular Dystrophy with a 7-kb Mini-Dystrophin Gene in the Canine Model.

    Science.gov (United States)

    Kodippili, Kasun; Hakim, Chady H; Pan, Xiufang; Yang, Hsiao T; Yue, Yongping; Zhang, Yadong; Shin, Jin-Hong; Yang, N Nora; Duan, Dongsheng

    2018-03-01

    Dual adeno-associated virus (AAV) technology was developed in 2000 to double the packaging capacity of the AAV vector. The proof of principle has been demonstrated in various mouse models. Yet, pivotal evidence is lacking in large animal models of human diseases. Here we report expression of a 7-kb canine ΔH2-R15 mini-dystrophin gene using a pair of dual AAV vectors in the canine model of Duchenne muscular dystrophy (DMD). The ΔH2-R15 minigene is by far the most potent synthetic dystrophin gene engineered for DMD gene therapy. We packaged minigene dual vectors in Y731F tyrosine-modified AAV-9 and delivered to the extensor carpi ulnaris muscle of a 12-month-old affected dog at the dose of 2 × 10 13 viral genome particles/vector/muscle. Widespread mini-dystrophin expression was observed 2 months after gene transfer. The missing dystrophin-associated glycoprotein complex was restored. Treatment also reduced muscle degeneration and fibrosis and improved myofiber size distribution. Importantly, dual AAV therapy greatly protected the muscle from eccentric contraction-induced force loss. Our data provide the first clear evidence that dual AAV therapy can be translated to a diseased large mammal. Further development of dual AAV technology may lead to effective therapies for DMD and many other diseases in human patients.

  1. Histotripsy of the Prostate for the Treatment of BPH: Chronic Results From a Canine Model

    Science.gov (United States)

    Hall, Timothy L.; Hempel, Chris R.; Lake, Alison M.; Kieran, Kathy; Ives, Kim; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2009-04-01

    Histotripsy was evaluated as a non-invasive BPH treatment. The prostates of 21 canine subjects were targeted with one of three histotripsy doses. Prostates were harvested immediately, 7 days, or 28 days after treatment and assessed for changes. Lower treatment doses were found to produced scattered cellular disruption and hemorrhage that was sometimes reversible. Higher doses perforated the urethra and produced cavities in the glandular prostate that healed to leave an enlarged urinary channel.

  2. A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data.

    Science.gov (United States)

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D; Cobb, Malcolm A; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  3. A predictive model for canine dilated cardiomyopathy—a meta-analysis of Doberman Pinscher data

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2015-03-01

    Full Text Available Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  4. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

    Directory of Open Access Journals (Sweden)

    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

  5. Complex functionality with minimal computation: Promise and pitfalls of reduced-tracer ocean biogeochemistry models

    Science.gov (United States)

    Galbraith, Eric D.; Dunne, John P.; Gnanadesikan, Anand; Slater, Richard D.; Sarmiento, Jorge L.; Dufour, Carolina O.; de Souza, Gregory F.; Bianchi, Daniele; Claret, Mariona; Rodgers, Keith B.; Marvasti, Seyedehsafoura Sedigh

    2015-12-01

    Earth System Models increasingly include ocean biogeochemistry models in order to predict changes in ocean carbon storage, hypoxia, and biological productivity under climate change. However, state-of-the-art ocean biogeochemical models include many advected tracers, that significantly increase the computational resources required, forcing a trade-off with spatial resolution. Here, we compare a state-of-the art model with 30 prognostic tracers (TOPAZ) with two reduced-tracer models, one with 6 tracers (BLING), and the other with 3 tracers (miniBLING). The reduced-tracer models employ parameterized, implicit biological functions, which nonetheless capture many of the most important processes resolved by TOPAZ. All three are embedded in the same coupled climate model. Despite the large difference in tracer number, the absence of tracers for living organic matter is shown to have a minimal impact on the transport of nutrient elements, and the three models produce similar mean annual preindustrial distributions of macronutrients, oxygen, and carbon. Significant differences do exist among the models, in particular the seasonal cycle of biomass and export production, but it does not appear that these are necessary consequences of the reduced tracer number. With increasing CO2, changes in dissolved oxygen and anthropogenic carbon uptake are very similar across the different models. Thus, while the reduced-tracer models do not explicitly resolve the diversity and internal dynamics of marine ecosystems, we demonstrate that such models are applicable to a broad suite of major biogeochemical concerns, including anthropogenic change. These results are very promising for the further development and application of reduced-tracer biogeochemical models that incorporate "sub-ecosystem-scale" parameterizations.

  6. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  7. Longitudinal quantification of the gingival crevicular fluid proteome during progression from gingivitis to periodontitis in a canine model.

    Science.gov (United States)

    Davis, Ian J; Jones, Andrew W; Creese, Andrew J; Staunton, Ruth; Atwal, Jujhar; Chapple, Iain L C; Harris, Stephen; Grant, Melissa M

    2016-07-01

    Inflammatory periodontal disease is widespread in dogs. This study evaluated site-specific changes in the canine gingival crevicular fluid (GCF) proteome during longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires general anaesthesia with associated risks and costs; our ultimate aim was to develop a periodontitis diagnostic for application in conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in dogs. Gingival crevicular fluid was sampled from a total of 10 teeth in eight dogs at three different stages of health/disease and samples prepared for quantitative mass spectrometry (data available via ProteomeXchange; identifier PXD003337). A univariate mixed model analysis determined significantly altered proteins between health states and six were evaluated by ELISA. Four hundred and six proteins were identified with 84 present in all samples. The prevalence of 40 proteins was found to be significantly changed in periodontitis relative to gingivitis. ELISA measurements confirmed that haptoglobin was significantly increased. This study demonstrates for the first time that proteins detected by mass spectrometry have potential to identify novel biomarkers for canine periodontal disease. Further work is required to validate additional biomarkers for a periodontitis diagnostic. © 2016 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  8. Lateral Cricoarytenoid Release: Development of a Novel Surgical Treatment Option for Adductor Spasmodic Dysphonia in a Canine Laryngeal Model.

    Science.gov (United States)

    Park, Andrea M; Paniello, Randal C

    2016-09-01

    To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). Experimental animal study. A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer-term studies and human trials are needed. © The Author(s) 2016.

  9. From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

    Science.gov (United States)

    Dietz, Volker; Schwab, Martin E

    2017-05-01

    Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

  10. The short and long term effects of intraoperative electron beam radiotherapy (IORT) on thoracic organs after pneumonectomy an experimental study in the canine model

    NARCIS (Netherlands)

    de Boer, Willem; Mehta, DM; Timens, W; Hoekstra, HJ

    1999-01-01

    Purpose: The tolerance of mediastinal structures and thoracic organs to intraoperative radiotherapy (IORT) was investigated in the canine model. Methods and Materials: Twenty-two adult beagles divided into three groups were subjected to a left pneumonectomy and IORT (10 MeV electrons) at doses of 20

  11. Radiation/hyperthermia in canine hemangiopericytomas: A large animal model for therapeutic response

    International Nuclear Information System (INIS)

    Richardson, R.C.; Anderson, V.L.; Voorhees, W.D. III; Blevins, W.E.; Inskeep, T.K.; Janas, W.; Shupe, R.E.; Babbs, C.F.

    1984-01-01

    X-irradiation followed by microwave induced hyperthermia resulted in a 91% objective response rate in 11 dogs with naturally occurring hemangiopericytomas. The authors used a novel statistical procedure to quantitatively evaluate the clinical behavior of locally invasive, non-metastatic tumors undergoing therapy for control of local disease. Utilizing a small sample size, the procedure demonstrated distribution of the data and classical parametric and non-parametric statistical methods, including setting confidence limits on the population mean and placing tolerance limits on a population percentage. Similarities of canine and human hemangiopericytomas were observed. Application of the statistical methods to human and animal trials were apparent

  12. Phase Behavior Modeling of Asphaltene Precipitation for Heavy Crudes: A Promising Tool Along with Experimental Data

    Science.gov (United States)

    Tavakkoli, M.; Kharrat, R.; Masihi, M.; Ghazanfari, M. H.; Fadaei, S.

    2012-12-01

    Thermodynamic modeling is known as a promising tool for phase behavior modeling of asphaltene precipitation under different conditions such as pressure depletion and CO2 injection. In this work, a thermodynamic approach is used for modeling the phase behavior of asphaltene precipitation. The precipitated asphaltene phase is represented by an improved solid model, while the oil and gas phases are modeled with an equation of state. The PR-EOS was used to perform flash calculations. Then, the onset point and the amount of precipitated asphaltene were predicted. A computer code based on an improved solid model has been developed and used for predicting asphaltene precipitation data for one of Iranian heavy crudes, under pressure depletion and CO2 injection conditions. A significant improvement has been observed in predicting the asphaltene precipitation data under gas injection conditions. Especially for the maximum value of asphaltene precipitation and for the trend of the curve after the peak point, good agreement was observed. For gas injection conditions, comparison of the thermodynamic micellization model and the improved solid model showed that the thermodynamic micellization model cannot predict the maximum of precipitation as well as the improved solid model. The non-isothermal improved solid model has been used for predicting asphaltene precipitation data under pressure depletion conditions. The pressure depletion tests were done at different levels of temperature and pressure, and the parameters of a non-isothermal model were tuned using three onset pressures at three different temperatures for the considered crude. The results showed that the model is highly sensitive to the amount of solid molar volume along with the interaction coefficient parameter between the asphaltene component and light hydrocarbon components. Using a non-isothermal improved solid model, the asphaltene phase envelope was developed. It has been revealed that at high temperatures, an

  13. A newly-designed temporary cardia stent for the treatment of achalasia:an experimental study in canine models

    International Nuclear Information System (INIS)

    Kuang Xiaochun; Cheng Yingsheng; Zhu Yueqi; Li Feng; Wang Weiguo

    2010-01-01

    Objective: To assess the efficacy and safety of a newly-designed temporary covered cardia stent for the treatment of achalasia in canine models and to investigate the histopathological changes at different points of follow-up time after the stent was removed. Methods: The canine achalasia model was created by injecting benzyl-dimethyl-tetradecyl ammonium chloride (BAC) circumferentially into the lower esophageal sphincter (LES) of the dogs. Twenty-four dogs with achalasia were randomly and equally divided into two groups with 12 dogs in each group: control group (using routine esophageal stents) and study group (using newly-designed temporary covered cardia stents). Under fluoroscopic guidance stents were implanted in the esophagus and were taken away from the esophagus 4 days after stent insertion in experimental dogs of both groups. LES pressures and timed barium esophagography (TBE) were performed in all dogs before and immediately after the stenting procedure, as well as at one week, 3 and 6 months after the stent was removed. Every three dogs were sacrificed each time at one week, 3 and 6 months after the stent was removed. The esophageal cardia was excised and sent for pathological examination. Results: All animals well tolerated the stent insertion / removal and the follow-up procedures. No severe complications such as esophageal perforation occurred. Comparison between two groups showed that stent migration occurrence was much lower in study group (n = 1) than that in control group (n = 5). The reduction of LES pressures in study group was more significant in comparison with control group (at 6-month follow-up, P = 0.027). The difference in barium column product (height x width) between 0-min and 5-min TBE was statistically significant in study group (at 3-month follow-up, P = 0.009). Integrated analysis of multi-comparison for LES pressures among subgroups of each group revealed that the dogs in study group exhibited better outcomes than the dogs in

  14. Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology.

    Science.gov (United States)

    Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; Dos Santos, Rodrigo Weber; Lobosco, Marcelo

    2017-02-01

    New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.

  15. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  16. Canine stifle joint biomechanics associated with tibial plateau leveling osteotomy predicted by use of a computer model.

    Science.gov (United States)

    Brown, Nathan P; Bertocci, Gina E; Marcellin-Little, Denis J

    2014-07-01

    To evaluate effects of tibial plateau leveling osteotomy (TPLO) on canine stifle joint biomechanics in a cranial cruciate ligament (CrCL)-deficient stifle joint by use of a 3-D computer model simulating the stance phase of gait and to compare biomechanics in TPLO-managed, CrCL-intact, and CrCL-deficient stifle joints. Computer simulations of the pelvic limb of a Golden Retriever. A previously developed computer model of the canine pelvic limb was used to simulate TPLO stabilization to achieve a tibial plateau angle (TPA) of 5° (baseline value) in a CrCL-deficient stifle joint. Sensitivity analysis was conducted for tibial fragment rotation of 13° to -3°. Ligament loads, relative tibial translation, and relative tibial rotation were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. TPLO with a 5° TPA converted cranial tibial translation to caudal tibial translation and increased loads placed on the remaining stifle joint ligaments, compared with results for a CrCL-intact stifle joint. Lateral collateral ligament load was similar, medial collateral ligament load increased, and caudal cruciate ligament load decreased after TPLO, compared with loads for a CrCL-deficient stifle joint. Relative tibial rotation after TPLO was similar to that of a CrCL-deficient stifle joint. Stifle joint biomechanics were affected by TPLO fragment rotation. In the model, stifle joint biomechanics were partially improved after TPLO, compared with CrCL-deficient stifle joint biomechanics, but TPLO did not fully restore CrCL-intact stifle joint biomechanics. Overrotation of the tibial fragment negatively influenced stifle joint biomechanics by increasing caudal tibial translation.

  17. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young; Yuk, Soon Hong; Lee, Yong Seok

    2005-01-01

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models

  18. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yuk, Soon Hong [Hannam University, College of Engineering, Daejeon (Korea, Republic of); Lee, Yong Seok [Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2005-07-15

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models.

  19. Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model

    Directory of Open Access Journals (Sweden)

    P.M.M. Dourado

    2006-06-01

    Full Text Available Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS. In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

  20. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

    Directory of Open Access Journals (Sweden)

    Melissa Paoloni

    Full Text Available Molecularly-guided trials (i.e. PMed now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77% successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days. Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical

  1. A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models.

    Science.gov (United States)

    Sniekers, Yvonne H; Intema, Femke; Lafeber, Floris P J G; van Osch, Gerjo J V M; van Leeuwen, Johannes P T M; Weinans, Harrie; Mastbergen, Simon C

    2008-02-12

    This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.

  2. Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

    Directory of Open Access Journals (Sweden)

    Kim M Boerkamp

    Full Text Available BACKGROUND: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. METHODS: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS and disseminated, visceral histiocytic sarcomas (VHS and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR analyses. RESULTS: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated, and GTSF1, Col3a1, CD90 and LUM (up-regulated in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. CONCLUSIONS: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.

  3. Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

    Science.gov (United States)

    Boerkamp, Kim M; van der Kooij, Marieke; van Steenbeek, Frank G; van Wolferen, Monique E; Groot Koerkamp, Marian J A; van Leenen, Dik; Grinwis, Guy C M; Penning, Louis C; Wiemer, Erik A C; Rutteman, Gerard R

    2013-01-01

    The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.

  4. The copepod Tigriopus: A promising marine model organism for ecotoxicology and environmental genomics

    Energy Technology Data Exchange (ETDEWEB)

    Raisuddin, Sheikh [Department of Chemistry and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Kwok, Kevin W.H. [Swire Institute of Marine Science, Department of Ecology and Biodiversity, University of Hong Kong, Pokfulam, Hong Kong (China); Leung, Kenneth M.Y. [Swire Institute of Marine Science, Department of Ecology and Biodiversity, University of Hong Kong, Pokfulam, Hong Kong (China); Schlenk, Daniel [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Lee, Jae-Seong [Department of Chemistry and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)]. E-mail: jslee2@hanyang.ac.kr

    2007-07-20

    There is an increasing body of evidence to support the significant role of invertebrates in assessing impacts of environmental contaminants on marine ecosystems. Therefore, in recent years massive efforts have been directed to identify viable and ecologically relevant invertebrate toxicity testing models. Tigriopus, a harpacticoid copepod has a number of promising characteristics which make it a candidate worth consideration in such efforts. Tigriopus and other copepods are widely distributed and ecologically important organisms. Their position in marine food chains is very prominent, especially with regard to the transfer of energy. Copepods also play an important role in the transportation of aquatic pollutants across the food chains. In recent years there has been a phenomenal increase in the knowledge base of Tigriopus spp., particularly in the areas of their ecology, geophylogeny, genomics and their behavioural, biochemical and molecular responses following exposure to environmental stressors and chemicals. Sequences of a number of important marker genes have been studied in various Tigriopus spp., notably T. californicus and T. japonicus. These genes belong to normal biophysiological functions (e.g. electron transport system enzymes) as well as stress and toxic chemical exposure responses (heat shock protein 20, glutathione reductase, glutathione S-transferase). Recently, 40,740 expressed sequenced tags (ESTs) from T. japonicus, have been sequenced and of them, 5673 ESTs showed significant hits (E-value, >1.0E-05) to the red flour beetle Tribolium genome database. Metals and organic pollutants such as antifouling agents, pesticides, polycyclic aromatic hydrocarbons (PAH) and polychrlorinated biphenyls (PCB) have shown reproducible biological responses when tested in Tigriopus spp. Promising results have been obtained when Tigriopus was used for assessment of risk associated with exposure to endocrine-disrupting chemicals (EDCs). Application of environmental

  5. The copepod Tigriopus: A promising marine model organism for ecotoxicology and environmental genomics

    International Nuclear Information System (INIS)

    Raisuddin, Sheikh; Kwok, Kevin W.H.; Leung, Kenneth M.Y.; Schlenk, Daniel; Lee, Jae-Seong

    2007-01-01

    There is an increasing body of evidence to support the significant role of invertebrates in assessing impacts of environmental contaminants on marine ecosystems. Therefore, in recent years massive efforts have been directed to identify viable and ecologically relevant invertebrate toxicity testing models. Tigriopus, a harpacticoid copepod has a number of promising characteristics which make it a candidate worth consideration in such efforts. Tigriopus and other copepods are widely distributed and ecologically important organisms. Their position in marine food chains is very prominent, especially with regard to the transfer of energy. Copepods also play an important role in the transportation of aquatic pollutants across the food chains. In recent years there has been a phenomenal increase in the knowledge base of Tigriopus spp., particularly in the areas of their ecology, geophylogeny, genomics and their behavioural, biochemical and molecular responses following exposure to environmental stressors and chemicals. Sequences of a number of important marker genes have been studied in various Tigriopus spp., notably T. californicus and T. japonicus. These genes belong to normal biophysiological functions (e.g. electron transport system enzymes) as well as stress and toxic chemical exposure responses (heat shock protein 20, glutathione reductase, glutathione S-transferase). Recently, 40,740 expressed sequenced tags (ESTs) from T. japonicus, have been sequenced and of them, 5673 ESTs showed significant hits (E-value, >1.0E-05) to the red flour beetle Tribolium genome database. Metals and organic pollutants such as antifouling agents, pesticides, polycyclic aromatic hydrocarbons (PAH) and polychrlorinated biphenyls (PCB) have shown reproducible biological responses when tested in Tigriopus spp. Promising results have been obtained when Tigriopus was used for assessment of risk associated with exposure to endocrine-disrupting chemicals (EDCs). Application of environmental

  6. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

    Science.gov (United States)

    Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

    2014-01-01

    Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (strategies may aid cancer drug development.

  7. American Canine Hepatozoonosis

    Science.gov (United States)

    Ewing, S. A.; Panciera, R. J.

    2003-01-01

    American canine hepatozoonosis (ACH) is a tick-borne disease that is spreading in the southeastern and south-central United States. Characterized by marked leukocytosis and periosteal bone proliferation, ACH is very debilitating and often fatal. Dogs acquire infection by ingesting nymphal or adult Gulf Coast ticks (Amblyomma maculatum) that, in a previous life stage, ingested the parasite in a blood meal taken from some vertebrate intermediate host. ACH is caused by the apicomplexan Hepatozoon americanum and has been differentiated from Old World canine hepatozoonosis caused by H. canis. Unlike H. canis, which is transmitted by the ubiquitous brown dog tick (Rhipicephalus sanguineus), H. americanum is essentially an accidental parasite of dogs, for which Gulf Coast ticks are not favored hosts. The geographic portrait of the disease parallels the known distribution of the Gulf Coast tick, which has expanded in recent years. Thus, the endemic cycle of H. americanum involves A. maculatum as definitive host and some vertebrate intermediate host(s) yet to be identified. Although coyotes (Canis latrans) are known to be infected, it is not known how important this host is in maintaining the endemic cycle. This review covers the biology of the parasite and of the tick that transmits it and contrasts ACH with classical canine hepatozoonosis. Clinical aspects of the disease are discussed, including diagnosis and treatment, and puzzling epidemiologic issues are examined. Brief consideration is given to the potential for ACH to be used as a model for study of angiogenesis and of hypertrophic osteoarthropathy. PMID:14557294

  8. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Tokihiro, E-mail: toyamamoto@ucdavis.edu [Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California 95817 (United States); Kent, Michael S.; Wisner, Erik R. [Department of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, California 95616 (United States); Johnson, Lynelle R.; Stern, Joshua A. [Department of Medicine and Epidemiology, University of California Davis School of Veterinary Medicine, Davis, California 95616 (United States); Qi, Lihong [Department of Public Health Sciences, University of California Davis, Davis, California 95616 (United States); Fujita, Yukio [Department of Radiation Oncology, Tokai University, Isehara, Kanagawa 259-1193 (Japan); Boone, John M. [Department of Radiology, University of California Davis School of Medicine, Sacramento, California 95817 (United States)

    2016-07-15

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  9. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model.

    Science.gov (United States)

    Yamamoto, Tokihiro; Kent, Michael S; Wisner, Erik R; Johnson, Lynelle R; Stern, Joshua A; Qi, Lihong; Fujita, Yukio; Boone, John M

    2016-07-01

    Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. The mean TRE

  10. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    International Nuclear Information System (INIS)

    Yamamoto, Tokihiro; Kent, Michael S.; Wisner, Erik R.; Johnson, Lynelle R.; Stern, Joshua A.; Qi, Lihong; Fujita, Yukio; Boone, John M.

    2016-01-01

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  11. Fuzzy promises

    DEFF Research Database (Denmark)

    Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas

    2012-01-01

    as narrative material to communicate self-identity. Finally, (c) we propose that brands deliver fuzzy experiential promises through effectively motivating consumers to adopt and play a social role implicitly suggested and facilitated by the brand. A promise is an inherently ethical concept and the article...... concludes with an in-depth discussion of fuzzy brand promises as two-way ethical commitments that put requirements on both brands and consumers....

  12. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C M; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J; Dhert, Wouter J A; Meij, Björn P; Creemers, Laura B.; Tryfonidou, Marianna A

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  13. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C. M.; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J.; Dhert, Wouter J. A.; Meij, Björn P.; Creemers, Laura B.; Tryfonidou, Marianna A.

    2017-01-01

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  14. In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research.

    Science.gov (United States)

    Desmet, Eline; Ramadhas, Anesh; Lambert, Jo; Van Gele, Mireille

    2017-06-01

    Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis

  15. Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model.

    Science.gov (United States)

    Boruch, Alan V; Nieponice, Alejandro; Qureshi, Irfan R; Gilbert, Thomas W; Badylak, Stephen F

    2010-06-15

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the constructive remodeling of several tissue types. Previous studies suggest that the ECM scaffold remodeling process is dependent on microenvironmental factors, including tissue-specific biomechanical loading. The objective of the present study was to evaluate the effects of long-term catheterization (LTC), with its associated inhibition of bladder filling and physiologic biomechanical loading, on ECM scaffold remodeling following partial cystectomy in a canine model. Reconstruction of the partial cystectomy site was performed using ECM scaffolds prepared from porcine small intestinal submucosa (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to either a long-term catheterization (LTC) group (n=5, catheterized 28 d) or a short-term catheterization group (STC, n=5, catheterized 24 h), and scaffold remodeling was assessed by histologic methods at 4 and 12 wk postoperatively. By 4 wk, animals in the STC group showed a well-developed and highly differentiated urothelium, a robust vascularization network, abundant smooth muscle actin (SMA), and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and many neuronal processes associated with newly formed arterioles. In contrast, at 4 wk the scaffolds in LTC animals were not epithelialized, and did not express neuronal markers. The scaffolds in the LTC group developed a dense granulation tissue containing SMA+, smMHC-, spindle-shaped cells that were morphologically and phenotypically consistent with myofibroblasts, but not smooth muscle cells. By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a constructive remodeling response, with a differentiated urothelium and islands of smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the scaffolds in LTC animals had a remodeling response more consistent with fibrosis even though catheters had been

  16. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon [University of Ulsan College of Medicine, Department of Radiology, Asan Medical Center, Seoul (Korea); Seo, Tae-Seok [Gachon Medical School, Department of Radiology, Gil Medical Center, Inchon (Korea); Yuk, Soon Hong [Hannam University, Department of Polymer Science and Engineering, College of Engineering, Daejeon (Korea); Kim, Young-Hwa [Soonchunhyang University Chonan Hospital, Department of Radiology, Chonan (Korea); Cho, Yong-Mee [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea)

    2005-06-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean{+-}standard deviation, 46.88{+-}23.75) than in the CS (73.75{+-}14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63{+-}2.05) than in CS (3.49{+-}2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  17. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon; Seo, Tae-Seok; Yuk, Soon Hong; Kim, Young-Hwa; Cho, Yong-Mee

    2005-01-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean±standard deviation, 46.88±23.75) than in the CS (73.75±14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63±2.05) than in CS (3.49±2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  18. Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

    Science.gov (United States)

    Fancher, R Marcus; Zhang, Hongjian; Sleczka, Bogdan; Derbin, George; Rockar, Richard; Marathe, Punit

    2011-07-01

    A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  19. Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

    Science.gov (United States)

    Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

    2009-10-09

    Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.

  20. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    Science.gov (United States)

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

  1. Endoscopic assessment and prediction of prostate urethral disintegration after histotripsy treatment in a canine model.

    Science.gov (United States)

    Schade, George R; Styn, Nicholas R; Hall, Timothy L; Roberts, William W

    2012-02-01

    Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1-3/prostate ≥1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking.

  2. Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism

    International Nuclear Information System (INIS)

    Reilly, C.F.; Fujita, T.; Hutzelmann, J.E.; Mayer, E.J.; Shebuski, R.J.

    1991-01-01

    Plasminogen activator inhibitor-1 (PAI-1), the specific, fast-acting inhibitor of tissue-type plasminogen activator (t-PA), binds to fibrin and has been found in high concentrations within arterial thrombi. These findings suggest that the localization of PAI-1 to a thrombus protects that same thrombus from fibrinolysis. In this study, clot-bound PAI-1 was assessed for its ability to suppress clot lysis in vivo. Autologous, canine whole blood clots were formed in the presence of increasing amounts of activated PAI-1 (0-30 micrograms/ml). Approximately 6-8% of the PAI-1 bound to the clots under the experimental conditions. Control and PAI-1-enriched clots containing iodine-125-labeled fibrin (ogen) were homogenized, washed to remove nonbound elements, and delivered to the lungs of anesthetized dogs where the homogenates subsequently underwent lysis by the endogeneous fibrinolytic system. 125I-labeled fibrin degradation products appeared in the blood of control animals within 10 minutes and were maximal by 90 minutes. PAI-1 reduced fibrin degradation product release in a dose-responsive manner at all times between 30 minutes and 5 hours (greater than or equal to 76% inhibition at 30 minutes, PAI-1 greater than or equal to 6 micrograms/ml). PAI-1 also suppressed D-dimer release from clots containing small amounts of human fibrin (ogen). t-PA administration attenuated the effects of PAI-1, whereas latent PAI-1 (20 micrograms/ml) had no effect on clot lysis. Blood levels of PA and PAI activity remained unaltered during these experiments. The results indicate that PAI-1 markedly inhibits endogenous fibrinolysis in vivo and, moreover, suggest that the localization of PAI-1 to a forming thrombus is an important physiological mechanism for subsequent thrombus stabilization

  3. Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

    Science.gov (United States)

    Choi, Chi-Bong; Kim, Sang-Young; Lee, Sung-Ho; Jahng, Geon-Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung-Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo-Suk

    2011-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. META 2f: Probabilistic, Compositional, Multi-dimension Model-Based Verification (PROMISE)

    Science.gov (United States)

    2011-10-01

    TTTech Computertechnik AG, and Vanderbilt University. PROMISE builds on the team’s unique expertise that combines a long history of successful...e.g. 0x800 for IPV4 , 0x806 for ARP, etc.) or as length field (value < 0x600), which indicates the actual length of the Ethernet data payload (46

  5. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Kristel Kegler

    Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

  6. Joint distraction in treatment of osteoarthritis (II): effects on cartilage in a canine model

    NARCIS (Netherlands)

    van Valburg, A. A.; van Roermund, P. M.; Marijnissen, A. C.; Wenting, M. J.; Verbout, A. J.; Lafeber, F. P.; Bijlsma, J. W.

    2000-01-01

    From a clinical point of view, joint distraction as a treatment for osteoarthritis (OA) of hip and ankle has been demonstrated to be very promising. Pain, joint mobility and functional ability, the most important factors for a patient with severe OA, all improved. Although radiographic joint space

  7. Canine thymoma

    International Nuclear Information System (INIS)

    Aronsohn, M.

    1985-01-01

    Thymoma is an uncommon canine neoplasm of thymic epithelial cells. It is seen in various breeds but may occur more frequently in German Shepherd Dogs. Middle-aged or older dogs can be affected and no sex predilection exists. A paraneoplastic syndrome of myasthenia gravis, nonthymic malignant tumors, and/or polymyositis occurs in a significant number of dogs with thymoma. Clinical signs are variable and are related to a space-occupying cranial mediastinal mass and/or manifestations of the paraneo-plastic syndrome. Dyspnea is the most common presenting clinical sign. Thoracic radiographs usually show a cranial mediastinal mass. Lymphoma is the main differential diagnosis. A definitive diagnosis may be made by closed biopsy but is more likely to be confirmed by thoracotomy. Thymomas may be completely contained within the thymic capsule or may spread by local invasion or metastasis. A staging system allows for an accurate prognosis and a therapeutic plan. Surgical removal of encapsulated thymomas may result in long-term survival or cure. Invasive or metastatic thymomas carry a guarded prognosis. Manifestations of the paraneoplastic syndrome complicate treatment. Adjuvant radiation and chemotherapy may be of value for advanced cases; however, adequate clinical trials have not been done in the dog

  8. Preclinical Multimodal Molecular Imaging Using 18F-FDG PET/CT and MRI in a Phase I Study of a Knee Osteoarthritis in In Vivo Canine Model

    Directory of Open Access Journals (Sweden)

    Maria I. Menendez DVM, PhD

    2017-03-01

    Full Text Available The aim of this study was to use a multimodal molecular imaging approach to serially assess regional metabolic changes in the knee in an in vivo anterior cruciate ligament transection (ACLT canine model of osteoarthritis (OA. Five canine underwent ACLT in one knee and the contralateral knee served as uninjured control. Prior, 3, 6, and 12 weeks post-ACLT, the dogs underwent 18F-fluoro-d-glucose (18F-FDG positron emission tomography (PET/computed tomography (CT and magnetic resonance imaging (MRI. The MRI was coregistered with the PET/CT, and 3-dimensional regions of interest (ROIs were traced manually and maximum standardized uptake values (SUVmax were evaluated. 18F-fluoro-d-glucose SUVmax in the ACLT knee ROIs was significantly higher compared to the uninjured contralateral knees at 3, 6, and 12 weeks. Higher 18F-FDG uptake observed in ACLT knees compared to the uninjured knees reflects greater metabolic changes in the injured knees over time. Knee 18F-FDG uptake in an in vivo ACLT canine model using combined PET/CT and MRI demonstrated to be highly sensitive in the detection of metabolic alterations in osseous and nonosteochondral structures comprising the knee joint. 18F-fluoro-d-glucose appeared to be a capable potential imaging biomarker for early human knee OA diagnosis, prognosis, and management.

  9. Chest wall reconstruction in a canine model using polydioxanone mesh, demineralized bone matrix and bone marrow stromal cells.

    Science.gov (United States)

    Tang, Hua; Xu, Zhifei; Qin, Xiong; Wu, Bin; Wu, Lihui; Zhao, XueWei; Li, Yulin

    2009-07-01

    Extensive chest wall defect reconstruction remains a challenging problem for surgeons. In the past several years, little progress has been made in this area. In this study, a biodegradable polydioxanone (PDO) mesh and demineralized bone matrix (DBM) seeded with osteogenically induced bone marrow stromal cells (BMSCs) were used to reconstruct a 6 cm x 5.5 cm chest wall defect. Four experimental groups were evaluated (n=6 per group): polydioxanone (PDO) mesh/DBMs/BMSCs group, polydioxanone (PDO) mesh/DBMs group, polydioxanone (PDO) mesh group, and a blank group (no materials) in a canine model. All the animals survived except those in the blank group. In all groups receiving biomaterial implants, the polydioxanone (PDO) mesh completely degraded at 24 weeks and was replaced by fibrous tissue with thickness close to that of the normal intercostal tissue (P>0.05). In the polydioxanone (PDO) mesh/DBMs/BMSCs group, new bone formation and bone-union were observed by radiographic and histological examination. More importantly, the reconstructed rib could maintain its original radian and achieve satisfactory biomechanics close to normal ribs in terms of bending stress (P>0.05). However, in the other two groups, fibrous tissue was observed in the defect and junctions, and the reconstructed ribs were easily distorted under an outer force. Based on these results, a surgical approach utilizing biodegradable polydioxanone (PDO) mesh in combination with DBMs and BMSCs could repair the chest wall defect not only in function but also in structure.

  10. Study on transcatheter ASD occlusion using modified atrial septal defect occluder with no stainless steel screw in canine model

    International Nuclear Information System (INIS)

    Xuan Bin; Qin Yongwen; Hu Jianqiang; Wu Hong

    2006-01-01

    Objective: To evaluate the safety, biocompatibility and efficacy of transcatheter closure of atrial septal defect (ASD) with no stainless-steel-screw occluder in canine model. Methods: The device was constructed from superelastic Nitinol wires tightly woven into two flat disks and sewed with polyester fibers inside, with a pliable loop on the right-atrial-disk of the device, connecting to the delivery cable. ASD was created by transcatheter puncture and balloon dilatation and then closed by occluder under fluoroscopy in the catheterization laboratory. the location and the influence of the implanted device on function of tricuspid valve and mitral valve were evaluated by echocardiography. At 1, 2, 3 and 6 months after the operation, the animals were killed and autopsy was conducted. Results: Eight dogs with puncture-produced ASD underwent ASD closing procedure successfully. the occluder showed no influence on the function of MV and AV demonstrated by echocardiogram. The two disks of the implanted device were covered with a smooth intact neogenesis layer in all dogs. Endocardial cells fully covered the surface of the two disk without inflammating reaction 3 months later. There was no evidence of corrosion on the surface of the nitinol wire removed from the dog after 6 months. Light microscopic examination of the liver, kidney, lung and spleen showed no evidence of embolization and inflammation. Conclusion: Transcatheter ASD occlusion with new-type occluder is safe, feasible, effective and good biocompatibility with a good prospective clinical application. (authors)

  11. Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

    Science.gov (United States)

    Noguchi, K; Matsuzaki, T; Ojiri, Y; Koyama, T; Nakasone, J; Sakanashi, M

    1998-01-01

    Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

  12. Uptake and distribution of a labeled fatty acid in a canine model of ischemia with and without reperfusion

    International Nuclear Information System (INIS)

    Devous, M.D. Sr.

    1985-01-01

    The relationship between regional myocardial blood flow (RMBF) and the regional distribution of 15-(4-iodophenyl)-9-methyl pentadecanoic acid (9-MPDA) was studied in a canine model of myocardial ischemia with and without reperfusion. Group 1 dogs received 135 min of left anterior descending coronary artery (LAD) occlusion; Group 2 dogs received 90 min of LAD occlusion and 45 min of reflow; and Group 3 dogs received 90 min of LAD occlusion and 3.5 hr of reperfusion. All animals received 9-MPDA 15 min prior to sacrifice, and tracer microspheres prior to occlusion, 5 and 80 min after occlusion, 15 min after reperfusion, and 15 min before the end of reperfusion. In Group 1 (permanent ischemia), 9-MPDA distribution was closely correlated with RMBF both 5 and 80 min after occlusion. In Group 2, 9-MPDA uptake was most closely correlated with reperfusion RMBF rather than ischemic RMBF. However, in 1 animal with good reperfusion, 9-MPDA uptake was reduced and was correlated with ischemic blood flow measured 5 min after occlusion. In Group 3, 9-MPDA uptake was correlated with RMBF measured during the ischemic period and not with reperfusion RMBF. It appears that 9-MPDA uptake is determined by RMBF when flow is limited, or early in reperfusion. With prolonged reperfusion, 9-MPDA uptake is significantly reduced in the ischemic zone in the presence of normal flow. This finding implies that the uptake of this fatty acid during reperfusion is related to myocardial damage (myocardial metabolism?) and not to RMBF

  13. In vivo biomechanical evaluation of a novel angle-stable interlocking nail design in a canine tibial fracture model.

    Science.gov (United States)

    Déjardin, Loïc M; Cabassu, Julien B; Guillou, Reunan P; Villwock, Mark; Guiot, Laurent P; Haut, Roger C

    2014-03-01

    To compare clinical outcome and callus biomechanical properties of a novel angle stable interlocking nail (AS-ILN) and a 6 mm bolted standard ILN (ILN6b) in a canine tibial fracture model. Experimental in vivo study. Purpose-bred hounds (n = 11). A 5 mm mid-diaphyseal tibial ostectomy was stabilized with an AS-ILN (n = 6) or an ILN6b (n = 5). Orthopedic examinations and radiographs were performed every other week until clinical union (18 weeks). Paired tibiae were tested in torsion until failure. Callus torsional strength and toughness were statistically compared and failure mode described. Total and cortical callus volumes were computed and statistically compared from CT slices of the original ostectomy gap. Statistical significance was set at P dogs (P dogs by 10 weeks and in 3/5 ILN6b dogs at 18 weeks. Callus mechanical properties were significantly greater in AS-ILN than ILN6b specimens by 77% (failure torque) and 166% (toughness). Failure occurred by acute spiral (control and AS-ILN) or progressive transverse fractures (ILN6b). Cortical callus volume was 111% greater in AS-ILN than ILN6b specimens (P < .05). Earlier functional recovery, callus strength and remodeling suggest that the AS-ILN provides a postoperative biomechanical environment more conducive to bone healing than a comparable standard ILN. © Copyright 2014 by The American College of Veterinary Surgeons.

  14. Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

    2003-12-01

    Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

  15. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  16. Development of a urinary lithiasis localizer mechanism to couple ultrasound and extracorporeal lithotripsy equipment in canine model

    Directory of Open Access Journals (Sweden)

    Enrico Andrade

    2006-10-01

    Full Text Available INTRODUCTION: Due to the evolution of extracorporeal lithotripsy equipment (ESWL and presently, the fact that most part of the equipment does not present ultrasound to localize urinary calculi, a system that allows adapting ultrasound equipment to ESWL equipment was developed, disposing only of fluoroscopy. Thus, this equipment was developed and was tested in urinary stones in canine models, to check its precision in relation to fluoroscopy. METHOD: Seven male dogs were utilized with the introduction, in the bladder through the ureteral route, of chalkstones, with initial localization by fluoroscopy, with a further ultrasound coincidence check localization of the vesical stones, being submitted to ESWL with a 3-hour, 21 days and 60 days follow-up after the procedure. RESULTS: Success of localization in all animals was verified presenting elimination of stones in the first micturitions, after ESWL. No complications were verified in those animals for 60 days. CONCLUSION: We verified that this equipment can lead to an update of the equipment that use only fluoroscopy, increasing in this way, their technical capacity in the treatment of urinary calculi, mainly in cases of non-radiopaque stones.

  17. Mechanical analysis of congestive heart failure caused by bundle branch block based on an electromechanical canine heart model

    Energy Technology Data Exchange (ETDEWEB)

    Dou Jianhong; Xia Ling; Zhang Yu; Shou Guofa [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Wei Qing; Liu Feng; Crozier, Stuart [School of Information Technology and Electrical Engineering, University of Queensland, St Lucia, Brisbane, Queensland 4072 (Australia)], E-mail: xialing@zju.edu.cn

    2009-01-21

    Asynchronous electrical activation, induced by bundle branch block (BBB), can cause reduced ventricular function. However, the effects of BBB on the mechanical function of heart are difficult to assess experimentally. Many heart models have been developed to investigate cardiac properties during BBB but have mainly focused on the electrophysiological properties. To date, the mechanical function of BBB has not been well investigated. Based on a three-dimensional electromechanical canine heart model, the mechanical properties of complete left and right bundle branch block (LBBB and RBBB) were simulated. The anatomical model as well as the fiber orientations of a dog heart was reconstructed from magnetic resonance imaging (MRI) and diffusion tensor MRI (DT-MRI). Using the solutions of reaction-diffusion equations and with a strategy of parallel computation, the asynchronous excitation propagation and intraventricular conduction in BBB was simulated. The mechanics of myocardial tissues were computed with time-, sarcomere length-dependent uniaxial active stress initiated at the time of depolarization. The quantification of mechanical intra- and interventricular asynchrony of BBB was then investigated using the finite-element method with an eight-node isoparametric element. The simulation results show that (1) there exists inter- and intraventricular systolic dyssynchrony during BBB; (2) RBBB may have more mechanical synchrony and better systolic function of the left ventricle (LV) than LBBB; (3) the ventricles always move toward the early-activated ventricle; and (4) the septum experiences higher stress than left and right ventricular free walls in BBB. The simulation results validate clinical and experimental recordings of heart deformation and provide regional quantitative estimates of ventricular wall strain and stress. The present work suggests that an electromechanical heart model, incorporating real geometry and fiber orientations, may be helpful for better

  18. Evaluation of Partial Transection versus Synovial Debridement of the ACL as Novel Canine Models for Management of ACL Injuries.

    Science.gov (United States)

    Bozynski, Chantelle C; Kuroki, Keiichi; Stannard, James P; Smith, Patrick A; Stoker, Aaron M; Cook, Cristi R; Cook, James L

    2015-10-01

    A major hurdle in investigating important clinical questions in knee ligament treatment is a lack of valid translational animal models. This study characterizes the effects of partial transection versus synovial debridement of the anterior (cranial) cruciate ligament (ACL) in dogs. A total of 27 adult purpose-bred research hounds underwent surgery and were assessed over the following 8 weeks. Dogs were randomized into the following three ACL status groups: sham control (n = 9), intact ACL with synovial debridement (exposed ACL) (n = 9), and partial transection of the ACL (partial tear ACL) (n = 9). Dogs in the exposed ACL group and partial tear ACL group had significantly (p < 0.05) more severe lameness, pain, effusion, reduced function, and reduced comfortable range of motion compared with controls, with the partial tear ACL group being most severely affected. More severe ACL and whole-joint pathology, and radiographic scores for osteoarthritis were present in the partial tear ACL group compared with exposed and/or sham control group. On the basis of these findings, biologic components of ACL injury (exposed ACL) played a role in whole-joint inflammation, but the clinical and pathological effects were more severe when both biologic and biomechanical components were present (i.e., partial tear ACL). These novel canine models were successfully developed to evaluate partial transection versus synovial debridement of the ACL and these models will be used to evaluate treatment options for acute management of ACL injuries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Ecological niche model of Phlebotomus perniciosus, the main vector of canine leishmaniasis in north-eastern Italy

    Directory of Open Access Journals (Sweden)

    Manuela Signorini

    2014-11-01

    Full Text Available With respect to the epidemiology of leishmaniasis, it is crucial to take into account the ecoclimatic and environ- mental characteristics that influence the distribution patterns of the vector sand fly species. It is also important to consider the possible impact of on-going climate changes on the emergence of this disease. In order to map the potential distribu- tion of Phlebotomus perniciosus, the main vector species of canine leishmaniasis in north-eastern Italy, geographical information systems tools, ecological niche models (ENM and remotely sensed environmental data were applied for a retrospective analysis of an entomological survey conducted in north-eastern Italy over 12 years. Sand fly trapping was conducted from 2001 to 2012 in 175 sites in the provinces of Veneto, Friuli-Venezia Giulia and Trentino-Alto Adige. We developed a predictive model of potential distribution of P. perniciosus using the maximum entropy algorithm software, based on seasonal normalized difference vegetation index, day and night land surface temperature, the Corine land cover 2006, a digital elevation model (GTOPO30 and climate layers obtained from the WorldClim database. The MaxEnt pre- diction found the more suitable habitat for P. perniciosus to be hilly areas (100-300 m above the mean sea level charac- terised by temperate climate during the winter and summer seasons, high winter vegetation cover and moderate rainfall during the activity season of vector sand fly. ENM provided a greater understanding of the geographical distribution and ecological requirements of P. perniciosus in the study area, which can be applied for the development of future surveil- lance strategies.

  20. Characterization of the canine urinary proteome.

    Science.gov (United States)

    Brandt, Laura E; Ehrhart, E J; Scherman, Hataichanok; Olver, Christine S; Bohn, Andrea A; Prenni, Jessica E

    2014-06-01

    Urine is an attractive biofluid for biomarker discovery as it is easy and minimally invasive to obtain. While numerous studies have focused on the characterization of human urine, much less research has focused on canine urine. The objectives of this study were to characterize the universal canine urinary proteome (both soluble and exosomal), to determine the overlap between the canine proteome and a representative human urinary proteome study, to generate a resource for future canine studies, and to determine the suitability of the dog as a large animal model for human diseases. The soluble and exosomal fractions of normal canine urine were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS). Biological Networks Gene Ontology (BiNGO) software was utilized to assign the canine urinary proteome to respective Gene Ontology categories, such as Cellular Component, Molecular Function, and Biological Process. Over 500 proteins were confidently identified in normal canine urine. Gene Ontology analysis revealed that exosomal proteins were largely derived from an intracellular location, while soluble proteins included both extracellular and membrane proteins. Exosome proteins were assigned to metabolic processes and localization, while soluble proteins were primarily annotated to specific localization processes. Several proteins identified in normal canine urine have previously been identified in human urine where these proteins are related to various extrarenal and renal diseases. The results of this study illustrate the potential of the dog as an animal model for human disease states and provide the framework for future studies of canine renal diseases. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

  1. Effects of traction on the blood circulation of femoral head: DSA study on a canine model

    International Nuclear Information System (INIS)

    Yang Xiujun; Xiao Jian; Ren Qile; Fu Shiping; Li Wei; Xiao Xiangsheng

    2010-01-01

    , group K, M and P, Group N and Q was 437.48, 30.25, 29.04, 132.69, 143.73, 25.20, respectively, and their P value was all <0.01. F value of femoral head circulation time among group A and B, group B and C, group B, D, E, F and G, Group H, I, J, L and O, group K, M and P, Group N and Q was 386.26, 31.83, 22.43, 141.94, 119.69, 21.68, respectively, and their P value was all <0.01. Conclusions: Traction could lead to ischemic response and circulation disorder of canine femoral head. The longer the traction time or the bigger the traction weight was, the poorer the femoral head perfusion and the longer the femoral head circulation time were, and the slower they recovered. DSA could directly reflect these changes in the femoral head with these angioarchitectural and hemodynamic indexes. (authors)

  2. The difference of canine, first and second premolar tooth size resulted from cone beam computed tomography imaging with Moyers Prediction Table on the working study model

    Directory of Open Access Journals (Sweden)

    Julies Hariani Sugiaman

    2011-03-01

    Full Text Available Model study is one of the standard orthodontic components which is important for diagnosis and treatment plan, but in some patients with the high gag reflex, it will be difficult to get this kind of study models. The existence of a new device which is able to show the condition of patients' mouth in three space areas (axial, sagittal, and coronal is expected to be an alternative when a study model is difficult to get. The purpose of this study is to find out whether or not there are any differences on the size of canine's mesiodistal, first and second premolar resulted from CBCT imaging with Moyers analysis on the study models. The method of the research is comparative descriptive. Measurements are made on 10 CBCT imaging results and 10 study models. The mesiodistal size, the result of CBCT imaging is measured by the available computer program and also the mesiodistal size of the study models is measured using a sliding compass, and then the size of canines, first and second premolar teeth resulted from CBCT imaging are compared to the result of Moyers method analysis on the study models. The t-test is used to find out if there is a difference between teeth size value between the CBCT imaging with the study models. The significance is determined based on the p-value t table.

  3. The Integration of Continuous and Discrete Latent Variable Models: Potential Problems and Promising Opportunities

    Science.gov (United States)

    Bauer, Daniel J.; Curran, Patrick J.

    2004-01-01

    Structural equation mixture modeling (SEMM) integrates continuous and discrete latent variable models. Drawing on prior research on the relationships between continuous and discrete latent variable models, the authors identify 3 conditions that may lead to the estimation of spurious latent classes in SEMM: misspecification of the structural model,…

  4. Absolute quantitation of myocardial blood flow with 201Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

    International Nuclear Information System (INIS)

    Iida, Hidehiro; Kim, Kyeong-Min; Nakazawa, Mayumi; Sohlberg, Antti; Zeniya, Tsutomu; Hayashi, Takuya; Watabe, Hiroshi; Eberl, Stefan; Tamura, Yoshikazu; Ono, Yukihiko

    2008-01-01

    201 Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99m Tc-labelled agents, such as 99m Tc-sestamibi and 99m Tc-tetrofosmine, the regional concentration of 201 Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201 Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201 Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K 1 ) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF SPECT ) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF MS ) (MBF SPECT = -0.067 + 1.042 x MBF MS , p 201 Tl and dynamic SPECT. (orig.)

  5. Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

    Science.gov (United States)

    Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

    2016-05-01

    Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

  6. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Directory of Open Access Journals (Sweden)

    Barbara C Rütgen

    Full Text Available Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL. Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-γ(c (-/- mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+, MHCII(+, CD11a(+ and CD79αcy(+. PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  7. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Science.gov (United States)

    Rütgen, Barbara C; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Murua Escobar, Hugo

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-)γ(c) (-/-) mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+), MHCII(+), CD11a(+) and CD79αcy(+). PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  8. Multi-body simulation of a canine hind limb: model development, experimental validation and calculation of ground reaction forces

    Directory of Open Access Journals (Sweden)

    Wefstaedt Patrick

    2009-11-01

    Full Text Available Abstract Background Among other causes the long-term result of hip prostheses in dogs is determined by aseptic loosening. A prevention of prosthesis complications can be achieved by an optimization of the tribological system which finally results in improved implant duration. In this context a computerized model for the calculation of hip joint loadings during different motions would be of benefit. In a first step in the development of such an inverse dynamic multi-body simulation (MBS- model we here present the setup of a canine hind limb model applicable for the calculation of ground reaction forces. Methods The anatomical geometries of the MBS-model have been established using computer tomography- (CT- and magnetic resonance imaging- (MRI- data. The CT-data were collected from the pelvis, femora, tibiae and pads of a mixed-breed adult dog. Geometric information about 22 muscles of the pelvic extremity of 4 mixed-breed adult dogs was determined using MRI. Kinematic and kinetic data obtained by motion analysis of a clinically healthy dog during a gait cycle (1 m/s on an instrumented treadmill were used to drive the model in the multi-body simulation. Results and Discussion As a result the vertical ground reaction forces (z-direction calculated by the MBS-system show a maximum deviation of 1.75%BW for the left and 4.65%BW for the right hind limb from the treadmill measurements. The calculated peak ground reaction forces in z- and y-direction were found to be comparable to the treadmill measurements, whereas the curve characteristics of the forces in y-direction were not in complete alignment. Conclusion In conclusion, it could be demonstrated that the developed MBS-model is suitable for simulating ground reaction forces of dogs during walking. In forthcoming investigations the model will be developed further for the calculation of forces and moments acting on the hip joint during different movements, which can be of help in context with the in

  9. Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma.

    Directory of Open Access Journals (Sweden)

    Ivaylo Gentschev

    Full Text Available Virotherapy using oncolytic vaccinia virus (VACV strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.

  10. Canine osteosarcoma cell lines contain stem-like cancer cells: biological and pharmacological characterization.

    Science.gov (United States)

    Gatti, Monica; Wurth, Roberto; Vito, Guendalina; Pattarozzi, Alessandra; Campanella, Chiara; Thellung, Stefano; Maniscalco, Lorella; De Maria, Raffaella; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Bajetto, Adriana; Ratto, Alessandra; Ferrari, Angelo; Barbieri, Federica; Florio, Tullio

    2016-05-01

    Cancer stem cells (CSCs) represent a small subpopulation of cells responsible for tumor formation and progression, drug resistance, tumor recurrence and metastasization. CSCs have been identified in many human tumors including osteosarcoma (OSA). CSC distinctive properties are the expression of stem cell markers, sustained growth, self-renewal and tumorigenicity. Here we report the isolation of stem-like cells from two canine OSA cultures, characterized by self-renewal, evaluated by sphere formation ability, differential marker expression, and in vitro proliferation when cultured in a medium containing EGF and bFGF. Current therapies for OSA increased survival time, but prognosis remains poor, due to the development of drug resistance and metastases. Chemotherapy shrinks the tumor mass but CSCs remain unaffected, leading to tumor recurrence. Metformin, a drug for type 2 diabetes, has been shown to possess antitumor properties affecting CSC survival in different human and animal cancers. Here we show that metformin has a significant antiproliferative effect on canine OSA stem-like cells, validating this in vitro model for further pre-clinical drug evaluations. In conclusion, our results demonstrate the feasibility of obtaining CSC-enriched cultures from primary canine OSA cells as a promising model for biological and pharmacological studies of canine and human OSAs.

  11. Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

    Science.gov (United States)

    Fernández-Trapero, María; Espejo-Porras, Francisco; Rodríguez-Cueto, Carmen; Coates, Joan R.; Pérez-Díaz, Carmen; de Lago, Eva; Fernández-Ruiz, Javier

    2017-01-01

    ABSTRACT Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells. PMID:28069688

  12. Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    María Fernández-Trapero

    2017-05-01

    Full Text Available Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS. The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM, caused by mutations in the superoxide dismutase 1 gene (SOD1. We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity. Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.

  13. Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis

    International Nuclear Information System (INIS)

    Qureshi, A.I.; Yahia, A.M.; Boulos, A.S.; Hanel, R.A.; Suri, M.F.K.; Hopkins, L.N.; Alberico, R.A.

    2004-01-01

    We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (IA) reteplase and intravenous (IV) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive IV alteplase 0.9 mg/kg over 60 min and IA placebo, or IA reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and IV placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the IV alteplase group and in five of seven in the IA reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with IV alteplase and three of seven treated with IA reteplase (P = 0.4). Intracerebral hemorrhage was more common in the IV alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that IA thrombolysis affords a recanalization rate similar to that of IV thrombolysis, but with a lower rate of intracerebral hemorrhage. (orig.)

  14. The establishment of atrial septal defect model with interventional management canine: its applied anatomy and technical points

    International Nuclear Information System (INIS)

    Zhu Yufeng; Huang Xinmiao; Bei Yuan; Wang Wei; Hu Jianqiang; Qin Yongwen

    2010-01-01

    Objective: To provide the relevant applied anatomic information for the preparation of atrial septal defect (ASD) model with transcatheter management in canine,and to discuss the technical points in making ASD model under DSA guidance. Methods: Anatomical measurements of the heart specimens,which were obtained from 15 healthy adult hybrid dogs (9 males and 6 females), were performed, from which the relevant anatomic parameters of the atrial septum were calculated. Cardiac 3D reconstruction with 64-sliced spiral CT scan was carried out in 5 dogs and the results were analyzed. According to the trans-illuminated position and angle obtained from 3D reconstruction images both the puncturing of the atrial septum with Brokenbrough needle and the balloon dilatation under fluoroscopic guidance were conducted in 20 dogs (body weight 17 -22 kg) to prepare ASD model. Results: The length and the width of the interauricular septum were (17.8 ± 4.3) mm and (14.5 ± 3.8) mm, respectively. The oval fossa was (11.2 ± 2.7) mm long and (8.7±1.9) mm wide. The distance from the central point of oval fossa to the central point of the orifice of coronary sinus was (7.2 ± 1.3) mm, which was (9.9 ± 1.5) mm to the center of the membranous atrial septum, (13.6 ± 3.1) mm to the middle point of septal tricuspid valve, (12.1 ± 2.3) mm to the central point of the bottom of aortic eminence and (11.3 ± 1.9) mm to the middle point of anterior bicuspid valve. The angle between atrial septal plane and sagittal plane was 15 degree ± 5 degree, and the angle between atrial septal plane and coronal plane was 75 degree ± 5 degree. Thus, the puncture of the interauricular septum was carried out with the dog in right anterior oblique position at 75 degree ± 5 degree. Of the total 20 dogs, ASD model was successfully established in 18, failure of the puncturing occurred in the remaining two, of which one died of cardiac tamponade after the procedure and the other one died of mistakenly puncturing

  15. Efficacy and safety of small intestinal submucosa in dural defect repair in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    He, Shu-kun [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 (China); Guo, Jin-hai [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 (China); Department of Orthopedics, The Third People' s Hospital of Chengdu, Chengdu, Sichuan 610031 (China); Wang, Zhu-le [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 (China); Zhang, Yi [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Tu, Yun-hu [Department of Neurosurgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083 (China); Wu, Shi-zhou [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China); Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 (China); Huang, Fu-guo [Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 (China); Xie, Hui-qi, E-mail: xiehuiqi@scu.edu.cn [Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041 (China)

    2017-04-01

    Dural defects are a common problem, and inadequate dural closure can lead to complications. Several types of dural substitute materials have recently been discarded or modified owing to poor biocompatibility or mechanical properties and adverse reactions. The small intestinal submucosa (SIS) is a promising material used in a variety of applications. Based on the limitations of previous studies, we conducted an animal study to evaluate the efficacy and safety of the SIS in preclinical trials. Twenty-four male beagle dogs were subjected to surgical resection to produce dural defects. SIS or autologous dural mater was patched on the dural defect. Gross and histological evaluations were carried out to evaluate the efficacy and safety of the therapy. Our findings demonstrated that the SIS, which stimulated connective and epithelial tissue responses for dural regeneration and functional recovery without immunological rejection, could provide prolonged defect repair and prevent complications. The mechanical properties of the SIS could be adjusted by application of multiple layers, and the biocompatibility of the material was appropriate. Thus, our data suggested that this material may represent an alternative option for clinical treatment of dural defects. - Highlights: • SIS stimulates dura regeneration without immunological rejection. • SIS has adjustable mechanical properties and appropriate biocompatibility. • SIS may be an effective alternative option for clinical treatment of dural defects.

  16. Efficacy and safety of small intestinal submucosa in dural defect repair in a canine model

    International Nuclear Information System (INIS)

    He, Shu-kun; Guo, Jin-hai; Wang, Zhu-le; Zhang, Yi; Tu, Yun-hu; Wu, Shi-zhou; Huang, Fu-guo; Xie, Hui-qi

    2017-01-01

    Dural defects are a common problem, and inadequate dural closure can lead to complications. Several types of dural substitute materials have recently been discarded or modified owing to poor biocompatibility or mechanical properties and adverse reactions. The small intestinal submucosa (SIS) is a promising material used in a variety of applications. Based on the limitations of previous studies, we conducted an animal study to evaluate the efficacy and safety of the SIS in preclinical trials. Twenty-four male beagle dogs were subjected to surgical resection to produce dural defects. SIS or autologous dural mater was patched on the dural defect. Gross and histological evaluations were carried out to evaluate the efficacy and safety of the therapy. Our findings demonstrated that the SIS, which stimulated connective and epithelial tissue responses for dural regeneration and functional recovery without immunological rejection, could provide prolonged defect repair and prevent complications. The mechanical properties of the SIS could be adjusted by application of multiple layers, and the biocompatibility of the material was appropriate. Thus, our data suggested that this material may represent an alternative option for clinical treatment of dural defects. - Highlights: • SIS stimulates dura regeneration without immunological rejection. • SIS has adjustable mechanical properties and appropriate biocompatibility. • SIS may be an effective alternative option for clinical treatment of dural defects.

  17. Melanin, a promising radioprotector: Mechanisms of actions in a mice model

    Energy Technology Data Exchange (ETDEWEB)

    Kunwar, A., E-mail: amitbio@rediffmail.com [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Adhikary, B. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Jayakumar, S. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Barik, A. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Chattopadhyay, S. [Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Raghukumar, S. [Myko Tech Private Limited, Dona Paula, Goa‐403004 (India); Priyadarsini, K.I., E-mail: kindira@barc.gov.in [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2012-10-15

    The radioprotective effect of extracellular melanin, a naturally occurring pigment, isolated from the fungus Gliocephalotrichum simplex was examined in BALB/C mice, and the probable mechanism of action was established. At an effective dose of 50 mg/kg body weight, melanin exhibited both prophylactic and mitigative activities, increasing the 30-day survival of mice by 100% and 60%, respectively, after exposure to radiation (7 Gy, whole body irradiation (WBI)). The protective activity of melanin was primarily due to inhibition of radiation-induced hematopoietic damages as evidenced by improvement in spleen parameters such as index, total cellularity, endogenous colony forming units, and maintenance of circulatory white blood cells and platelet counts. Melanin also reversed the radiation-induced decrease in ERK phosphorylation in splenic tissue, which may be the key feature in its radioprotective action. Additionally, our results indicated that the sustained activation of AKT, JNK and P38 proteins in splenic tissue of melanin pre-treated group may also play a secondary role. This was also supported by the fact that melanin could prevent apoptosis in splenic tissue by decreasing BAX/Bcl-XL ratio, and increasing the expressions of the proliferation markers (PCNA and Cyclin D1), compared to the radiation control group. Melanin also reduced the oxidative stress in hepatic tissue and abrogated immune imbalance by reducing the production of pro-inflammatory cytokines (IL6 and TNFα). In conclusion, our results confirmed that fungal melanin is a very effective radioprotector against WBI and the probable mechanisms of radioprotection are due to modulation in pro-survival (ERK) signaling, prevention of oxidative stress and immunomodulation. -- Highlights: ► Melanin showed promising radioprotection under pre and post irradiation condition. ► Melanin protects the hematopoietic system from radiation induced damage. ► Melanin modulates pro-survival pathways, immune system

  18. A Posteriori Comparison of Natural and Surgical Destabilization Models of Canine Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Maxim Moreau

    2013-01-01

    Full Text Available For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA. Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought.

  19. A Posteriori Comparison of Natural and Surgical Destabilization Models of Canine Osteoarthritis

    Science.gov (United States)

    Pelletier, Jean-Pierre; d'Anjou, Marc-André; Blond, Laurent; Pelletier, Johanne-Martel; del Castillo, Jérôme R. E.

    2013-01-01

    For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA). Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought. PMID:24288664

  20. Feasibility study of corticosteroid treatment for esophageal ulcer after EMR in a canine model.

    Science.gov (United States)

    Honda, Michitaka; Nakamura, Tatsuo; Hori, Yoshio; Shionoya, Yoshiki; Yamamoto, Kazumichi; Nishizawa, Yuji; Kojima, Fumitsugu; Shigeno, Keiji

    2011-07-01

    Intralesional or systemic steroid administration is a promising strategy for the prevention of esophageal stricture after endoscopic therapy. The aim of this study was to evaluate the influence of steroid therapy on the process of healing of defects in the esophageal mucosa after endoscopic mucosal resection (EMR). Nine beagle dogs were divided into three equal groups: group A, intralesional injection (n = 3), group B, peroral administration (n = 3), and group C, untreated control (n = 3). In group A, triamcinolone acetonide 1 ml (10 mg) was injected directly into the exposed submucosal layer immediately after EMR, and again on postoperative day (POD) 7. In group B, dogs were administered prednisolone 0.5 mg/kg/day orally for 14 days after EMR. In group C, 1 ml normal saline was injected by the same method as that used for group A. On POD 28, histological examination was performed to evaluate epithelialization, inflammation, angiogenesis, and atrophy of the muscularis propria. In groups A, B, and C, the mean ulcer area was 50.1, 22.7, and 7.4 mm(2), respectively. The difference between groups A and C was significant (p < 0.01). Inflammatory cells were significantly more evident in the lesions of group A than in those of group C (p < 0.05). In all groups, atrophy of the muscularis propria was evident. However, transmural destruction and fibrosis were observed only in group A. It was speculated that the esophageal ulcer causes the fibrosis of the submucosa and atrophy of the muscularis propria during process of healing. Intralesional steroid injection deepened the esophageal ulcers and delayed epithelialization, whereas systemic administration did not clearly improve the lesion healing process.

  1. Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

    Science.gov (United States)

    Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

    2016-09-01

    Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model.

    Science.gov (United States)

    Tsumanuma, Yuka; Iwata, Takanori; Kinoshita, Atsuhiro; Washio, Kaoru; Yoshida, Toshiyuki; Yamada, Azusa; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Izumi, Yuichi

    2016-01-01

    Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of β-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest that

  3. A Cell Kinetic Model of Granulocytopoiesis Under Radiation Exposure: Extension from Murines to Canines and Humans

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2009-01-01

    Space radiation poses significant challenges to space travel, and it is essential to understand the possible adverse effects from space radiation exposure to the radiosensitive organ systems that are important for immediate survival of human, e.g., the hematopoietic system. In this presentation a biomathematical model of granulocytopoiesis is described and used to analyze the blood granulocyte changes seen in the blood of mammalians under continuous and acute radiation exposure. This is one of a set of hematopoietic models that have been successfully utilized to simulate and interpret the experimental data of acute and chronic radiation on rodents. We discuss the underlying implicit regulation mechanism and the biological relevance of the kinetic parameters estimation method. Extension of the model to predictions in dogs and humans systems indicates that the modeling results are consistent with the cumulative experimental and empirical data from various sources. This implies the potential to integrate the models into one united system for monitoring the hematopoietic response of various species under irradiation. Based on the evidence of threshold responses of dogs to extended periods of low daily dose exposures, we discuss the potential health risks of the space traveler under chronic stress of low-dose irradiation and the possibly encountered Solar Particle Events.

  4. Promises from Afar: A Model of International Student Psychological Contract in Business Education

    Science.gov (United States)

    Bordia, Sarbari; Bordia, Prashant; Restubog, Simon Lloyd D.

    2015-01-01

    Despite their significant presence in western business schools, the needs and experiences of international students have not been adequately reflected in the business education literature. We draw upon psychological contract theory--used to understand employer-employee relationships--to develop a novel theoretical model on the international…

  5. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  6. Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, Hedwig S.; Chen, Chen; Geijsen, Niels; Oosterhoff, Loes A.; van Wolferen, Monique E.; Pelaez, Nicolas; Fieten, Hille; Wubbolts, Richard W.; Grinwis, Guy C.; Chan, Jefferson; Huch, Meritxell; Vries, Robert R. G.; Clevers, Hans; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C.; Schotanus, Baukje A.

    2015-01-01

    The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease

  7. Assessment of left ventricular mechanical dyssynchrony in left bundle branch block canine model: Comparison between cine and tagged MRI.

    Science.gov (United States)

    Saporito, Salvatore; van Assen, Hans C; Houthuizen, Patrick; Aben, Jean-Paul M M; Strik, Marc; van Middendorp, Lars B; Prinzen, Frits W; Mischi, Massimo

    2016-10-01

    To compare cine and tagged magnetic resonance imaging (MRI) for left ventricular dyssynchrony assessment in left bundle branch block (LBBB), using the time-to-peak contraction timing, and a novel approach based on cross-correlation. We evaluated a canine model dataset (n = 10) before (pre-LBBB) and after induction of isolated LBBB (post-LBBB). Multislice short-axis tagged and cine MRI images were acquired using a 1.5 T scanner. We computed contraction time maps by cross-correlation, based on the timing of radial wall motion and of circumferential strain. Finally, we estimated dyssynchrony as the standard deviation of the contraction time over the different regions of the myocardium. Induction of LBBB resulted in a significant increase in dyssynchrony (cine: 13.0 ± 3.9 msec for pre-LBBB, and 26.4 ± 5.0 msec for post-LBBB, P = 0.005; tagged: 17.1 ± 5.0 msec at for pre-LBBB, and 27.9 ± 9.8 msec for post-LBBB, P = 0.007). Dyssynchrony assessed by cine and tagged MRI were in agreement (r = 0.73, P = 0.0003); differences were in the order of time difference between successive frames of 20 msec (bias: -2.9 msec; limit of agreement: 10.1 msec). Contraction time maps were derived; agreement was found in the contraction patterns derived from cine and tagged MRI (mean difference in contraction time per segment: 3.6 ± 13.7 msec). This study shows that the proposed method is able to quantify dyssynchrony after induced LBBB in an animal model. Cine-assessed dyssynchrony agreed with tagged-derived dyssynchrony, in terms of magnitude and spatial direction. J. MAGN. RESON. IMAGING 2016;44:956-963. © 2016 International Society for Magnetic Resonance in Medicine.

  8. Kind discipline: Developing a conceptual model of a promising school discipline approach.

    Science.gov (United States)

    Winkler, Jennifer L; Walsh, Michele E; de Blois, Madeleine; Maré, Jeannette; Carvajal, Scott C

    2017-06-01

    This formative evaluation develops a novel conceptual model for a discipline approach fostering intrinsic motivation and positive relationships in schools. We used concept mapping to elicit and integrate perspectives on kind discipline from teachers, administrators, and other school staff. Three core themes describing kind discipline emerged from 11 identified clusters: (1) proactively developing a positive school climate, (2) responding to conflict with empathy, accountability, and skill, and (3) supporting staff skills in understanding and sharing expectations. We mapped the identified components of kind discipline onto a social ecological model and found that kind discipline encompasses all levels of that model including the individual, relational, environmental/structural, and even community levels. This contrasts with the dominant individual-behavioral discipline approaches that focus on fewer levels and may not lead to sustained student and staff motivation. The findings illustrate the importance of setting and communicating clear expectations and the need for them to be collaboratively developed. Products of the analysis and synthesis reported here are operationalized materials for teachers grounded in a "be kind" culture code for classrooms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A critical examination of the youth foyer model for alleviating homelessness: Strengthening a promising evidence base

    Directory of Open Access Journals (Sweden)

    Iris Levin

    2015-12-01

    Full Text Available This article assesses the quality of 15 primary studies that examined the effectiveness of youth foyer or foyer-like programs on the lives of young homeless people. The youth foyer model provides an integrated approach to tackling youth homelessness, connecting affordable accommodation to training and employment. In Australia, there is growing support from government for the development and funding of foyer programs. However to date, there has been very limited development and investment in the evidence base on the effectiveness of this model in Australia or internationally. Following an extensive literature search, we argue that there is a need to lift the standard of the evidence base of youth foyer effectiveness. We discuss two main issues: the difficulty studies had validating claims of foyer effectiveness, and limitations of research design and methodology. The implications of the lack of rigour in the research reviewed are three-fold. Firstly, youth foyer evaluation study quality could be improved by: clearer methodological and model documentation; post intervention follow-up design; comparison of data to non-randomised comparison groups; and a pre-publication peer-review process. This would be supported with clearer expectations from the research community regarding the production and assessment of grey literature. Secondly, while the standard of reporting needs to be raised, the ‘gold standard’ (i.e. randomised controlled trials of research design in the scientific community is not a relevant benchmark in the field of homelessness research. This is due to the complexity of homelessness interventions and the inadequate funding of the homelessness research field. Greater investment in robust research and evaluation should accompany the substantial investment in youth foyer programs in order to accurately appraise the effectiveness of the youth foyer model. Thirdly, the lack of rigour in the studies reviewed suggests gaps in the service

  10. Maxillary growth in a congenital cleft palate canine model for surgical research.

    Science.gov (United States)

    Paradas-Lara, Irene; Casado-Gómez, Inmaculada; Martín, Conchita; Martínez-Sanz, Elena; López-Gordillo, Yamila; González, Pablo; Rodríguez-Bobada, Cruz; Chamorro, Manuel; Arias, Pablo; Maldonado, Estela; Ortega, Ricardo; Berenguer, Beatriz; Martínez-Álvarez, Concepción

    2014-01-01

    We have recently presented the Old Spanish Pointer dog, with a 15-20% spontaneous congenital cleft palate rate, as a unique experimental model of this disease. This study aimed to describe the cleft palate of these dogs for surgical research purposes and to determine whether congenital cleft palate influences maxillofacial growth. Seven newborn Old Spanish Pointer dogs of both sexes, comprising a cleft palate group (n = 4) and a normal palate group (n = 3), were fed using the same technique. Macroscopic photographs and plaster casts from the palate, lateral radiographs and computer tomograms of the skull were taken sequentially over 41 weeks, starting at week 5. The cleft morphology, the size and the tissue characteristics in these dogs resembled the human cleft better than current available animal models. During growth, the cleft width varies. Most of the transverse and longitudinal measures of the palate were statistically lower in the cleft palate group. The cleft palate group showed hypoplasia of the naso-maxillary complex. This model of congenital cleft palate seems suitable for surgical research purposes. A reduced maxillofacial pre- and post-natal development is associated to the congenital cleft palate in the Old Spanish Pointer dog. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  11. Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies

    Science.gov (United States)

    Kornegay, Joe N.; Bogan, Janet R.; Bogan, Daniel J.; Childers, Martin K.; Li, Juan; Nghiem, Peter; Detwiler, David A.; Larsen, C. Aaron; Grange, Robert W.; Bhavaraju-Sanka, Ratna K.; Tou, Sandra; Keene, Bruce P.; Howard, James F.; Wang, Jiahui; Fan, Zheng; Schatzberg, Scott J.; Styner, Martin A.; Flanigan, Kevin M.; Xiao, Xiao; Hoffman, Eric P.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified. PMID:22218699

  12. Promise and problems in using stress triggering models for time-dependent earthquake hazard assessment

    Science.gov (United States)

    Cocco, M.

    2001-12-01

    Earthquake stress changes can promote failures on favorably oriented faults and modify the seismicity pattern over broad regions around the causative faults. Because the induced stress perturbations modify the rate of production of earthquakes, they alter the probability of seismic events in a specified time window. Comparing the Coulomb stress changes with the seismicity rate changes and aftershock patterns can statistically test the role of stress transfer in earthquake occurrence. The interaction probability may represent a further tool to test the stress trigger or shadow model. The probability model, which incorporate stress transfer, has the main advantage to include the contributions of the induced stress perturbation (a static step in its present formulation), the loading rate and the fault constitutive properties. Because the mechanical conditions of the secondary faults at the time of application of the induced load are largely unkown, stress triggering can only be tested on fault populations and not on single earthquake pairs with a specified time delay. The interaction probability can represent the most suitable tool to test the interaction between large magnitude earthquakes. Despite these important implications and the stimulating perspectives, there exist problems in understanding earthquake interaction that should motivate future research but at the same time limit its immediate social applications. One major limitation is that we are unable to predict how and if the induced stress perturbations modify the ratio between small versus large magnitude earthquakes. In other words, we cannot distinguish between a change in this ratio in favor of small events or of large magnitude earthquakes, because the interaction probability is independent of magnitude. Another problem concerns the reconstruction of the stressing history. The interaction probability model is based on the response to a static step; however, we know that other processes contribute to

  13. Current practices and research updates on diabetes mellitus in canine

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar

    2014-11-01

    Full Text Available Diabetes has evidence in ancient literatures, though recently is being considered as one amongst the most emerging disease condition in both human and companion animals. Diabetes mellitus is one of the common endocrinopathy of dog characterized by hyperglycemia, glycosuria and weight loss. Reports suggests high fraction of canine population suffer with diabetes world over. Studies in different veterinary hospitals of United States suggest increase in cases of canine diabetes and decrease in case fatality rate over time. Increase in cases of canine diabetes worldwide is attributed to awareness amongst pet owners, better veterinary health facilities, breed preferences by dog owners, increase dependence on commercial feeds, obesity, etc. Diabetes in most dogs is immune mediated and insulin dependent. Breed predisposition in canine is attributed to dog leukocyte antigen gene pool encoding form major histocompatibility complex-II molecules, however research is still underway. Diagnosis of diabetes still relies on blood sugar evaluation for screening of canine population, though many other diagnostic methods have shown promising benefits including measurement of fructosamine and glycated haemoglobin. Management of diabetes in dog is based on insulin therapy, diet modification and exercise. Use of oral anti-diabetics drugs in canine is limited though experimental studies have shown promising results. Alternative therapies have been explored, but only a few approaches have shown promise for clinical application.

  14. Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model.

    Science.gov (United States)

    Burattini, R; Sipkema, P; van Huis, G A; Westerhof, N

    1985-01-01

    This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A "back"-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7 X 10(-12) m4s2kg-1, intramyocardial compliance 110 X 10(-12)m4s2kg-1, and resistance 7.5 X 10(9) kgm-4s-1. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.

  15. No more non-model species: the promise of next generation sequencing for comparative immunology.

    Science.gov (United States)

    Dheilly, Nolwenn M; Adema, Coen; Raftos, David A; Gourbal, Benjamin; Grunau, Christoph; Du Pasquier, Louis

    2014-07-01

    Next generation sequencing (NGS) allows for the rapid, comprehensive and cost effective analysis of entire genomes and transcriptomes. NGS provides approaches for immune response gene discovery, profiling gene expression over the course of parasitosis, studying mechanisms of diversification of immune receptors and investigating the role of epigenetic mechanisms in regulating immune gene expression and/or diversification. NGS will allow meaningful comparisons to be made between organisms from different taxa in an effort to understand the selection of diverse strategies for host defence under different environmental pathogen pressures. At the same time, it will reveal the shared and unique components of the immunological toolkit and basic functional aspects that are essential for immune defence throughout the living world. In this review, we argue that NGS will revolutionize our understanding of immune responses throughout the animal kingdom because the depth of information it provides will circumvent the need to concentrate on a few "model" species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2.

    Science.gov (United States)

    Ito, K; Miyamoto, R; Tani, H; Kurita, S; Kobayashi, M; Tamura, K; Bonkobara, M

    2018-02-01

    Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS. © 2017 John Wiley & Sons Ltd.

  17. A novel, ring-connected stent versus conventional GI stents: comparative study of physical properties and migration rates in a canine colon obstruction model.

    Science.gov (United States)

    Park, Hong Suk; Choo, In Wook; Seo, Soowon; Hyun, Dongho; Lim, Sooyoun; Kim, Jae J; Hong, Saet-Byul; Min, Byung-Hoon; Do, Young Soo; Choo, Sung Wook; Shin, Sung Wook; Park, Kwang Bo; Cho, Sung Ki

    2015-01-01

    Migration of stents is one of the most common adverse events in covered stent placement in GI tract obstruction. To compare physical property and migration rates in a canine colon obstruction model among a novel stent and conventional stents. Comparative physical test and animal study. Medical device testing laboratory and animal laboratory. Mongrel dogs (N=26). Surgical colon obstruction followed by placement of a novel (n=13) or conventional (n=13) stent. Physical properties, migration, and adverse events. The novel stent showed better flexibility, as in a physical test of longitudinal compressibility and axial force, than did conventional stents, and it withstood the fatigue test for 10 days. In terms of radial force and tensile strength, the novel stent showed the same or better results than conventional stents. In a canine colon obstruction model, the migration rate of a novel stent was significantly lower than that of a conventional stent (2/13, 15.4% vs 8/13, 61.5%; P=.008). Animal study of limited size. The novel, ring-connected stent is more flexible and more resistant to migration than the conventional stents. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  18. EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model.

    Directory of Open Access Journals (Sweden)

    Kichang Han

    Full Text Available To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS for suppressing granulation tissue formation after stent placement in a canine urethral model.All experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS group received NFCSs and the drug stent (DS group received EW-7197 (1000 μg-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test.Stent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p 0.05.The EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

  19. Structural and in vivo mechanical characterization of canine patellar cartilage: a closed chondromalacia patellae model.

    Science.gov (United States)

    LaBerge, M; Audet, J; Drouin, G; Rivard, C H

    1993-01-01

    The purpose of this project was to study the relationship between the structure of the patellar cartilage and its response to static compressive loading with a closed chondromalacia patellae model. An animal model was used to induce degeneration of the patella that was monitored quantitatively and qualitatively as a function of time. Ten adult mongrel dogs had their left patellofemoral groove replaced by a customized metallic implant covered with a thin film of polyethylene for periods of 3 months (five dogs) and 6 months (five dogs). An indenter was designed to perform mechanical indentation testing on the patellar cartilage in situ. The animals were anesthetized and the response of patellar cartilage to a static compressive load of 4.5 MPa was monitored for 20 min and its relaxation after load removal for 20 min. Indentation tests were performed every 3 months of the implantation period. At the end of the implantation period, the patellae were processed for histology, and sections were stained with Safranin-O indicative of the proteoglycans content. Macroscopically, no apparent degeneration or fibrillation of the patellar surfaces was observed after 3 or 6 months of implantation. However, the patellar surface showed a change in coloration after 6 months. A 17 +/- 3% and 37 +/- 8% deformation of the cartilage were calculated for the 3-month and 6-month specimens, respectively. Histologically, a progressive loss of proteoglycans was observed in the matrix as a function of implantation time. These results indicated that an increase in cartilage compliance is associated with an intrinsic remodeling of the cartilage matrix and that these changes might occur without external signs of degeneration and can be quantified.

  20. Characterization of a canine model of glycogen storage disease type IIIa

    Directory of Open Access Journals (Sweden)

    Haiqing Yi

    2012-11-01

    Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

  1. Promise(s of mesenchymal stem cells as an in vitro model system to depict pre-diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.

    Directory of Open Access Journals (Sweden)

    Soundarya L Madhira

    Full Text Available BACKGROUND: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants, established at National Centre for Laboratory Animals (NCLAS of National Institute of Nutrition (NIN, form a suitable model system to study obesity with Type 2 diabetes (T2D demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc. The present study has been carried out to explore the potent application(s of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs, to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT, hyperinsulinemia (HI and insulin resistance (IR seen with Mutant rats akin to human situation. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of BM-MSCs (third passage from Mutants, its lean littermate (Lean and parental control (Control were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs. The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFα; increased stem cell recruitment (Oct-4, Sox-2 and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation; accelerated preadipocyte induction (Dact-1, PPARγ2 with a quantitative increase in mature adipocyte formation (Leptin; ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data. CONCLUSIONS: Given the ease of accessibility and availability of MSCs, the present study form the basis to report for

  2. Influence of Overt Diabetes Mellitus on Cyclosporine Pharmacokinetics in a Canine Model

    Directory of Open Access Journals (Sweden)

    Khalid M. Alkharfy

    2009-01-01

    Full Text Available Background/Aims. Diabetic patients usually require more medications than their nondiabetic counterparts. This work examined the effect of hyperglycemia on the pharmacokinetic properties of cyclosporine in a diabetic dog model. Main Methods. Diabetes was induced using a streptozotocin/alloxan combination and verified by measuring the serum glucose level. Cyclosporine was administered as a bolus intravenous dose of 5 mg/kg, and blood samples were collected at different time points for determining drug concentrations and biochemical analyses. Results. Diabetic dogs showed a significant increase in total body clearance of cyclosporine compared to healthy controls (0.457 L hr−1Kg−1 versus 0.201 L hr−1Kg−1, =.0019 and a decrease in its biological half-life (9.32 hours versus 22.56 hours, =.0125. In addition, diabetic animals exhibited a higher total cholesterol (7.20±0.62 mmol/L and 5.28±0.36 mmol/L; <.05 as well as more serum low density lipoproteins (4.45±0.72 mmol/L versus 1.06±0.10 mmol/L; <.05. Conclusion. Overt diabetes alters cyclosporine disposition by modulating its clearance. Abnormalities in the lipid profile, among other factors, may contribute to the accelerated metabolic degradation of cyclosporine under hyperglycemic conditions.

  3. Acute Management of Anterior Cruciate Ligament Injuries Using Novel Canine Models.

    Science.gov (United States)

    Bozynski, Chantelle C; Stannard, James P; Smith, Pat; Hanypsiak, Bryan T; Kuroki, Keiichi; Stoker, Aaron; Cook, Cristi; Cook, James L

    2016-10-01

    The objective of this study was to compare treatment options for acute management of anterior cruciate ligament (ACL) injuries using preclinical models. Twenty-seven adult purpose-bred research hounds underwent knee surgery (sham control, exposed ACL, or partial-tear ACL) and were assessed over the following 8 weeks. Dogs were randomized into three treatment groups: standard of care (i.e., rest and nonsteroidal anti-inflammatory drugs [NSAIDs]), washout, or leukoreduced platelet-rich plasma (PRP) so that a total of nine dogs received each treatment. Data from the two ACL-injury groups were pooled for each treatment ( n  = 6 per treatment group) and analyzed for treatment effects. The washout and PRP groups experienced less lameness, pain, and effusion, and greater function and comfortable range of motion compared with the NSAID group, with the PRP group showing most benefits. PRP was associated with the lowest severity of ACL pathology based on arthroscopic assessment. Measurable levels of inflammatory and degradative biomarkers were present in synovial fluid with significant differences noted over time. Based on these findings, washout had positive clinical effects compared with the standard-of-care group especially within the first week of treatment, but became less beneficial over time. A single injection of leukoreduced PRP was associated with favorable clinical results. However, no treatment was significantly "protective" against progression toward osteoarthritis after ACL injury. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Evaluation of tumor motion effect in canine model for diagnostic and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sangkeun; Nam, Taewon; Kim, Kyeongmin [Molecular Imaging Research Center, Seoul (Korea, Republic of); Park, Seungwoo; Han, Suchul; Ji, Younghoon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Nohwon; Eom, Kidong [Konkuk Univ., Seoul (Korea, Republic of)

    2013-05-15

    The internal organs move up to 35mm maximum and it provides information and uncertainty that has been distorted in the diagnosis and treatment. Previous most studies for the effect of respiration have been performed with external monitoring systems but it cannot represent internal organ motion such as liver, pancreas, and lung. Positron emission tomography (PET) is more influenced by motion than computed tomography (CT) and magnetic resonance imaging (MRI) since measurement time for image acquisition is longer than CT and MRI. Thus, count of tumor is to be underestimated and region of tumor is to be overestimated. The first aim of this study was developing the artificial pulmonary nodule which can be performed non-invasive transplant into thorax of dogs and second is to assess the effect of respiratory motion on PET image with evaluating the applicability of the artificial model using dogs for diagnosis and treatment. The developed artificial pulmonary nodule showed reproducibility and motion effect as respiratory cycle and it was verified in PET images. Radiation dose estimated was not changed and was reduced slightly of 10 rpm and 15 rpm, respectively, in both of glass dosimeter and ion chamber. The developed artificial pulmonary nodule will be useful tool for evaluating respiratory motion and better research performance for diagnosis and treatment will be expected with performing simulated experiment using the nodule conducted in this study.

  5. Efficacy of a laparoscopic gastric restrictive device in an obese canine model.

    Science.gov (United States)

    Guo, Xiaomei; Mattar, Samer G; Mimms, Scott E; Navia, Jose A; Kassab, Ghassan S

    2014-01-01

    Bariatric surgery using laparoscopic techniques is the most effective treatment for morbid obesity. The objective of the study is to assess the safety and efficacy of a novel laparoscopic reversible gastric restrictive (RGR) device in a group of obese dogs. An implant was also performed in a cadaver to assess implant feasibility in a human. Four obese mongrel dogs were subjected to RGR implantation for 3 months followed by recovery for an additional 6 weeks after device removal. Food intake, body weight, radiographic barium imaging, and gastric endoscopy were used to monitor RGR performance before implant, after implant, and implant removal. An additional RGR laparoscopic implantation procedure was performed in a human cadaver. The implanted obese dogs exhibited a significant decrease in food intake and body weight over 3 months with the RGR device. The reduction of food intake was sustained at an average of 46 % after implant and the excess weight loss reached an average of 75 % at the end of 12 weeks with recovery to approximately 78 % of baseline after 6 weeks of implant removal. Barium imaging and gastric endoscopy both confirmed passage for food through the restrictive device channel in the stomach. The RGR device was successfully implanted laparoscopically on the cadaver stomach in less than an hour. The RGR device is laparoscopically deliverable and removable with effective and sustainable weight loss over a 12-week period in an obese dog model. The implant is also technically feasible in man.

  6. Long-term following-up of viability of spleen autotransplants in the Beagle canine model.

    Science.gov (United States)

    Sajtos, Erika; Balint, Anita; Brath, Endre; Nemeth, Norbert; Peto, Katalin; Kovacs, Judit; Galuska, Laszlo; Varga, Jozsef; Fodor, Zoltan; Furka, Istvan; Miko, Iren

    2012-02-01

    To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique). Prior to operations, on the 1(st) postoperative week, monthly till the 6(th) as well as in the 9(th) and 12(th) month, hemorheological examinations were performed. In postoperative 12(th) month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. From the 4(th)-5(th) postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleen-autotransplants was similar to normal splenic tissue. The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.

  7. Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

    International Nuclear Information System (INIS)

    Johnstone, Peter A. S.; DeLuca, Anne Marie; Bacher, John D.; Hampshire, Victoria A.; Terrill, Richard E.; Anderson, William J.; Kinsella, Timothy J.; Sindelar, William F.

    1995-01-01

    Purpose: The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Methods and Materials: Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. Results: All animals treated with ≥ 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED 50 ) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Conclusions: Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED 50 determined here is in keeping with data from other animal trials, and from clinical trials in humans

  8. Diaphragm remodeling and compensatory respiratory mechanics in a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Mead, A F; Petrov, M; Malik, A S; Mitchell, M A; Childers, M K; Bogan, J R; Seidner, G; Kornegay, J N; Stedman, H H

    2014-04-01

    Ventilatory insufficiency remains the leading cause of death and late stage morbidity in Duchenne muscular dystrophy (DMD). To address critical gaps in our knowledge of the pathobiology of respiratory functional decline, we used an integrative approach to study respiratory mechanics in a translational model of DMD. In studies of individual dogs with the Golden Retriever muscular dystrophy (GRMD) mutation, we found evidence of rapidly progressive loss of ventilatory capacity in association with dramatic morphometric remodeling of the diaphragm. Within the first year of life, the mechanics of breathing at rest, and especially during pharmacological stimulation of respiratory control pathways in the carotid bodies, shift such that the primary role of the diaphragm becomes the passive elastic storage of energy transferred from abdominal wall muscles, thereby permitting the expiratory musculature to share in the generation of inspiratory pressure and flow. In the diaphragm, this physiological shift is associated with the loss of sarcomeres in series (∼ 60%) and an increase in muscle stiffness (∼ 900%) compared with those of the nondystrophic diaphragm, as studied during perfusion ex vivo. In addition to providing much needed endpoint measures for assessing the efficacy of therapeutics, we expect these findings to be a starting point for a more precise understanding of respiratory failure in DMD.

  9. Cameroon mid-level providers offer a promising public health dentistry model

    Directory of Open Access Journals (Sweden)

    Achembong Leo

    2012-11-01

    Full Text Available Background Oral health services are inadequate and unevenly distributed in many developing countries, particularly those in sub-Saharan Africa. Rural areas in these countries and poorer sections of the population in urban areas often do not have access to oral health services mainly because of a significant shortage of dentists and the high costs of care. We reviewed Cameroon’s experience with deploying a mid-level cadre of oral health professionals and the feasibility of establishing a more formal and predictable role for these health workers. We anticipate that a task-shifting approach in the provision of dental care will significantly improve the uneven distribution of oral health services particularly in the rural areas of Cameroon, which is currently served by only 3% of the total number of dentists. Methods The setting of this study was the Cameroon Baptist Convention Health Board (BCHB, which has four dentists and 42 mid-level providers. De-identified data were collected manually from the registries of 10 Baptist Convention clinics located in six of Cameroon’s 10 regions and then entered into an Excel format before importing into STATA. A retrospective abstraction of all entries for patient visits starting October 2010, and going back in time until 1500 visits were extracted from each clinic. Results This study showed that mid-level providers in BCHB clinics are offering a full scope of dental work across the 10 clinics, with the exception of treatment for major facial injuries. Mid-level providers alone performed 93.5% of all extractions, 87.5% of all fillings, 96.5% of all root canals, 97.5% of all cleanings, and 98.1% of all dentures. The dentists also typically played a teaching role in training the mid-level providers. Conclusions The Ministry of Health in Cameroon has an opportunity to learn from the BCHB model to expand access to oral health care across the country. This study shows the benefits of using a simple, workable, low

  10. Finite element analysis of rapid canine retraction through reducing resistance and distraction

    Directory of Open Access Journals (Sweden)

    Junjie XUE

    2014-01-01

    Full Text Available Objective: The aims of this study were to compare different surgical approaches to rapid canine retraction by designing and selecting the most effective method of reducing resistance by a three-dimensional finite element analysis. Material and Methods: Three-dimensional finite element models of different approaches to rapid canine retraction by reducing resistance and distraction were established, including maxillary teeth, periodontal ligament, and alveolar. The models were designed to dissect the periodontal ligament, root, and alveolar separately. A 1.5 N force vector was loaded bilaterally to the center of the crown between first molar and canine, to retract the canine distally. The value of total deformation was used to assess the initial displacement of the canine and molar at the beginning of force loading. Stress intensity and force distribution were analyzed and evaluated by Ansys 13.0 through comparison of equivalent (von Mises stress and maximum shear stress. Results: The maximum value of total deformation with the three kinds of models occurred in the distal part of the canine crown and gradually reduced from the crown to the apex of the canine; compared with the canines in model 3 and model 1, the canine in model 2 had the maximum value of displacement, up to 1.9812 mm. The lowest equivalent (von Mises stress and the lowest maximum shear stress were concentrated mainly on the distal side of the canine root in model 2. The distribution of equivalent (von Mises stress and maximum shear stress on the PDL of the canine in the three models was highly concentrated on the distal edge of the canine cervix. . Conclusions: Removal of the bone in the pathway of canine retraction results in low stress intensity for canine movement. Periodontal distraction aided by surgical undermining of the interseptal bone would reduce resistance and effectively accelerate the speed of canine retraction.

  11. Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Lygia M.M. Malvestio

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE, Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD.

  12. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure

    DEFF Research Database (Denmark)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T

    2014-01-01

    AIMS: The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore...... the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. METHODS AND RESULTS: An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF...... ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease...

  13. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

    Science.gov (United States)

    Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

    2013-01-01

    Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

  14. TRE ~ANGUAGE LOTTERY: PROMISES, PROMISES ...

    African Journals Online (AJOL)

    dual children, about which expressions a certain child heard and registered and with what frequency at ... scientific theorizing, suggested the need for another model, allowing d simpler account of the phenotype or .... (1) generate base structures, which are mapped to abstract S-structures including trace by tranSformations,.

  15. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

    2016-04-01

    The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

  16. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

    Science.gov (United States)

    Willems, Nicole; Yang, Hsiao-Yin; Langelaan, Marloes L P; Tellegen, Anna R; Grinwis, Guy C M; Kranenburg, Hendrik-Jan C; Riemers, Frank M; Plomp, Saskia G M; Craenmehr, Eric G M; Dhert, Wouter J A; Papen-Botterhuis, Nicole E; Meij, Björn P; Creemers, Laura B; Tryfonidou, Marianna A

    2015-08-20

    Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant

  17. Biomechanics of an orthosis-managed cranial cruciate ligament-deficient canine stifle joint predicted by use of a computer model.

    Science.gov (United States)

    Bertocci, Gina E; Brown, Nathan P; Mich, Patrice M

    2017-01-01

    OBJECTIVE To evaluate effects of an orthosis on biomechanics of a cranial cruciate ligament (CrCL)-deficient canine stifle joint by use of a 3-D quasistatic rigid-body pelvic limb computer model simulating the stance phase of gait and to investigate influences of orthosis hinge stiffness (durometer). SAMPLE A previously developed computer simulation model for a healthy 33-kg 5-year-old neutered Golden Retriever. PROCEDURES A custom stifle joint orthosis was implemented in the CrCL-deficient pelvic limb computer simulation model. Ligament loads, relative tibial translation, and relative tibial rotation in the orthosis-stabilized stifle joint (baseline scenario; high-durometer hinge]) were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. Sensitivity analysis was conducted to evaluate the influence of orthosis hinge stiffness on model outcome measures. RESULTS The orthosis decreased loads placed on the caudal cruciate and lateral collateral ligaments and increased load placed on the medial collateral ligament, compared with loads for the CrCL-intact stifle joint. Ligament loads were decreased in the orthosis-managed CrCL-deficient stifle joint, compared with loads for the CrCL-deficient stifle joint. Relative tibial translation and rotation decreased but were not eliminated after orthosis management. Increased orthosis hinge stiffness reduced tibial translation and rotation, whereas decreased hinge stiffness increased internal tibial rotation, compared with values for the baseline scenario. CONCLUSIONS AND CLINICAL RELEVANCE Stifle joint biomechanics were improved following orthosis implementation, compared with biomechanics of the CrCL-deficient stifle joint. Orthosis hinge stiffness influenced stifle joint biomechanics. An orthosis may be a viable option to stabilize a CrCL-deficient canine stifle joint.

  18. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    Science.gov (United States)

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  19. Complete chloroplast genome sequence of green foxtail (Setaria viridis), a promising model system for C4 photosynthesis.

    Science.gov (United States)

    Wang, Shuo; Gao, Li-Zhi

    2016-09-01

    The complete chloroplast genome of green foxtail (Setaria viridis), a promising model system for C4 photosynthesis, is first reported in this study. The genome harbors a large single copy (LSC) region of 81 016 bp and a small single copy (SSC) region of 12 456  bp separated by a pair of inverted repeat (IRa and IRb) regions of 22 315 bp. GC content is 38.92%. The proportion of coding sequence is 57.97%, comprising of 111 (19 duplicated in IR regions) unique genes, 71 of which are protein-coding genes, four are rRNA genes, and 36 are tRNA genes. Phylogenetic analysis indicated that S. viridis was clustered with its cultivated species S. italica in the tribe Paniceae of the family Poaceae. This newly determined chloroplast genome will provide valuable genetic resources to assist future studies on C4 photosynthesis in grasses.

  20. Upper canine inclination influences the aesthetics of a smile.

    Science.gov (United States)

    Bothung, C; Fischer, K; Schiffer, H; Springer, I; Wolfart, S

    2015-02-01

    This current study investigated which angle of canine inclination (angle between canine tooth axis (CA-line) and the line between the lateral canthus and the ipsilateral labial angle (EM-line)) is perceived to be most attractive in a smile. The second objective was to determine whether laymen and dental experts share the same opinion. A Q-sort assessment was performed with 48 posed smile photographs to obtain two models of neutral facial attractiveness. Two sets of images (1 male model set, 1 female model set), each containing seven images with incrementally altered canine and posterior teeth inclinations, were generated. The images were ranked for attractiveness by three groups (61 laymen, 59 orthodontists, 60 dentists). The images with 0° inclination, that is CA-line (maxillary canine axis) parallel to EM-line (the line formed by the lateral canthus and the ipsilateral corner of the mouth) (male model set: 54·4%; female model set: 38·9%), or -5° (inward) inclination (male model set: 20%; female model set: 29·4%) were perceived to be most attractive within each set. Images showing inward canine inclinations were regarded to be more attractive than those with outward inclinations. Dental experts and laymen were in accordance with the aesthetics. Smiles were perceived to be most attractive when the upper canine tooth axis was parallel to the EM-line. In reconstructive or orthodontic therapy, it is thus important to incline canines more inwardly than outwardly. © 2014 John Wiley & Sons Ltd.

  1. Collateral ventilation quantification using xenon-enhanced dynamic dual-energy CT: Differences between canine and swine models of bronchial occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chng Min [Dept. of Radiology, Seoul National University College of Medicine and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8 +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4 +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

  2. Collateral ventilation quantification using xenon-enhanced dynamic dual-energy CT: Differences between canine and swine models of bronchial occlusion

    International Nuclear Information System (INIS)

    Kim, Eun Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chng Min

    2015-01-01

    The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8 +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4 +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

  3. Characterization of STAT3 activation and expression in canine and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Li Pui-Kai

    2009-03-01

    Full Text Available Abstract Background Dysregulation of signal transducer and activator of transcription 3 (STAT3 has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. Methods To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656 or STAT3 (LLL3 inhibitors and cell proliferation (CyQUANT, caspase 3/7 activity (ELISA, apoptosis (Western blotting for PARP cleavage and/or viability (Wst-1 were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Results Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known

  4. Characterization of STAT3 activation and expression in canine and human osteosarcoma

    International Nuclear Information System (INIS)

    Fossey, Stacey L; Liao, Albert T; McCleese, Jennifer K; Bear, Misty D; Lin, Jiayuh; Li, Pui-Kai; Kisseberth, William C; London, Cheryl A

    2009-01-01

    Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3. These data

  5. Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

    2014-08-01

    Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was

  6. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  7. Acute and chronic sensitivity to copper of a promising ecotoxicological model species, the annual killifish Nothobranchius furzeri.

    Science.gov (United States)

    Philippe, Charlotte; Grégoir, Arnout F; Janssens, Lizanne; Pinceel, Tom; De Boeck, Gudrun; Brendonck, Luc

    2017-10-01

    Nothobranchius furzeri is a promising model for ecotoxicological research due to the species' short life cycle and the production of drought-resistant eggs. Although the species is an emerging vertebrate fish model for several fundamental as well as applied research domains, its potential for ecotoxicological research has not yet been tested. The aim of this study was to characterise the acute and chronic sensitivity of this species to copper as compared to other model organisms. Effects of both acute and chronic copper exposure were tested on survival, life history and physiological traits. We report a 24h-LC 50 of 53.93µg Cu/L, which is situated within the sensitivity range of other model species such as Brook Trout, Fathead Minnow and Rainbow Trout. Moreover, in the full life cycle exposure, we show that an exposure concentration of 10.27µg/L did not cause acute adverse effects (96h), but did cause mortality after prolonged exposure (3-4 weeks). Also chronic, sublethal effects were observed, such as a reduction in growth rate, delayed maturation and postponed reproduction. Based on our results, we define the NOEC at 6.68µg Cu/L, making N. furzeri more sensitive to copper as compared to Brook Trout and Fathead Minnow. We found stimulatory effects on peak fecundity at subinhibitory levels of copper concentrations (hormesis). Finally, we found indications for detoxifying and copper-excreting mechanisms, demonstrating the ability of the fish to cope with this essential metal, even when exposed to stressful amounts. The successful application of current ecotoxicological protocols on N. furzeri and its sensitivity range comparable to that of other model organisms forms the basis to exploit this species in further ecotoxicological practices. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence

    Science.gov (United States)

    Wolf, Zena T.; Leslie, Elizabeth J.; Arzi, Boaz; Jayashankar, Kartika; Karmi, Nili; Jia, Zhonglin; Rowland, Douglas J.; Young, Amy; Safra, Noa; Sliskovic, Saundra; Murray, Jeffrey C.; Wade, Claire M.; Bannasch, Danika L.

    2014-01-01

    Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb–29.3 Mb; praw = 4.64×10−15). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans. PMID:24699068

  9. Vasodilative effects of prostaglandin E1 derivate on arteries of nerve roots in a canine model of a chronically compressed cauda equina

    Directory of Open Access Journals (Sweden)

    Konno Shin-ichi

    2008-04-01

    Full Text Available Abstract Background Reduction of blood flow is important in the induction of neurogenic intermittent claudication (NIC in lumbar spinal canal stenosis. PGE1 improves the mean walking distance in patients with NIC type cauda equina compression. PGE1 derivate might be effective in dilating blood vessels and improving blood flow in nerve roots with chronically compressed cauda equina. The aim of this study was to assess whether PGE1 derivate has vasodilatory effects on both arteries and veins in a canine model of chronic cauda equina compression. Methods Fourteen dogs were used in this study. A plastic balloon inflated to 10 mmHg was placed under the lamina of the 7th lumbar vertebra for 1 week. OP-1206-cyclodextrin clathrate (OP-1206-CD: prostaglandin E1 derivate was administered orally. The blood vessels of the second or third sacral nerve root were identified using a specially designed surgical microscope equipped with a video camera. The diameter of the blood vessels was measured on video-recordings every 15 minutes until 90 minutes after the administration of the PGE1 derivate. Results We observed seven arteries and seven veins. The diameter and blood flow of the arteries was significantly increased compared with the veins at both 60 and 75 minutes after administration of the PGE1 derivate (p Discussion The PGE1 derivate improved blood flow in the arteries but did not induce blood stasis in the veins. Our results suggest that the PGE1 derivate might be a potential therapeutic agent, as it improved blood flow in the nerve roots in a canine model of chronic cauda equina compression.

  10. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Canine tooth size and fitness in male mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Leigh, Steven R; Setchell, Joanna M; Charpentier, Marie; Knapp, Leslie A; Wickings, E Jean

    2008-07-01

    Sexual selection theory explains the evolution of exaggerated male morphologies and weaponry, but the fitness consequences of developmental and age-related changes in these features remain poorly understood. This long-term study of mandrill monkeys (Mandrillus sphinx) demonstrates how age-related changes in canine tooth weaponry and adult canine size correlate closely with male lifetime reproductive success. Combining long-term demographic and morphometric data reveals that male fitness covaries simply and directly with canine ontogeny, adult maximum size, and wear. However, fitness is largely independent of other somatometrics. Male mandrills sire offspring almost exclusively when their canines exceed approximately 30 mm, or two-thirds of average adult value (45 mm). Moreover, sires have larger canines than nonsires. The tooth diminishes through wear as animals age, corresponding with, and perhaps influencing, reproductive senescence. These factors combine to constrain male reproductive opportunities to a brief timespan, defined by the period of maximum canine length. Sexually-selected weaponry, especially when it is nonrenewable like the primate canine tooth, is intimately tied to the male life course. Our analyses of this extremely dimorphic species indicate that sexual selection is closely intertwined with growth, development, and aging, pointing to new directions for sexual selection theory. Moreover, the primate canine tooth has potential as a simple mammalian system for testing genetically-based models of aging. Finally, the tooth may record details of life histories in fossil primates, especially when sexual selection has played a role in the evolution of dimorphism.

  12. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  13. Evaluation of (99)  (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99)  (m)Tc-sestamibi.

    Science.gov (United States)

    Bu, Lihong; Li, Renfei; Jin, Zhongnan; Wen, Xiaofei; Liu, Shuang; Yang, Baofeng; Shen, Baozhong; Chen, Xiaoyuan

    2011-02-01

    (99)  (m)TcN-MPO ([(99)  (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99)  (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99)  (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Five normal mongrel dogs were injected intravenously with (99)  (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99)  (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99)  (m)TcN-MPO (n = 4) or (99)  (m)Tc-Sestamibi (n = 4). It was found that (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi both showed good

  14. The perils and promises of microbial abundance: novel natures and model ecosystems, from artisanal cheese to alien seas.

    Science.gov (United States)

    Paxson, Heather; Helmreich, Stefan

    2014-04-01

    Microbial life has been much in the news. From outbreaks of Escherichia coli to discussions of the benefits of raw and fermented foods to recent reports of life forms capable of living in extreme environments, the modest microbe has become a figure for thinking through the presents and possible futures of nature, writ large as well as small. Noting that dominant representations of microbial life have shifted from an idiom of peril to one of promise, we argue that microbes--especially when thriving as microbial communities--are being upheld as model ecosystems in a prescriptive sense, as tokens of how organisms and human ecological relations with them could, should, or might be. We do so in reference to two case studies: the regulatory politics of artisanal cheese and the speculative research of astrobiology. To think of and with microbial communities as model ecosystems offers a corrective to the scientific determinisms we detect in some recent calls to attend to the materiality of scientific objects.

  15. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  16. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F

    2011-01-01

    Canine prostatic tumours exhibit similarities to those of man and may represent a useful model system to explore the mechanisms of cancer progression. Tumour progression to malignancy requires a change from an epithelial phenotype to a fibroblastic or mesenchymal phenotype. Vimentin expression...... is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...... that the acquisition of the epithelial-mesenchymal transition phenotype in canine prostatic carcinoma may be characterized by the presence of mesenchymal intermediate filament (vimentin) that could lead to a higher likelihood of metastasis....

  17. A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application to Normal and Diseased Canine Left Ventricles

    Science.gov (United States)

    Choi, Young Joon; Constantino, Jason; Vedula, Vijay; Trayanova, Natalia; Mittal, Rajat

    2015-01-01

    A methodology for the simulation of heart function that combines an MRI-based model of cardiac electromechanics (CE) with a Navier–Stokes-based hemodynamics model is presented. The CE model consists of two coupled components that simulate the electrical and the mechanical functions of the heart. Accurate representations of ventricular geometry and fiber orientations are constructed from the structural magnetic resonance and the diffusion tensor MR images, respectively. The deformation of the ventricle obtained from the electromechanical model serves as input to the hemodynamics model in this one-way coupled approach via imposed kinematic wall velocity boundary conditions and at the same time, governs the blood flow into and out of the ventricular volume. The time-dependent endocardial surfaces are registered using a diffeomorphic mapping algorithm, while the intraventricular blood flow patterns are simulated using a sharp-interface immersed boundary method-based flow solver. The utility of the combined heart-function model is demonstrated by comparing the hemodynamic characteristics of a normal canine heart beating in sinus rhythm against that of the dyssynchronously beating failing heart. We also discuss the potential of coupled CE and hemodynamics models for various clinical applications. PMID:26442254

  18. Evaluation of Left Ventricular Diastolic Dysfunction with Early Systolic Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Canine Heart Failure Model.

    Science.gov (United States)

    Wu, Wei-Chun; Ma, Hong; Xie, Rong-Ai; Gao, Li-Jian; Tang, Yue; Wang, Hao

    2016-04-01

    This study evaluated the role of two-dimensional speckle tracking echocardiography (2DSTE) for predicting left ventricular (LV) diastolic dysfunction in pacing-induced canine heart failure. Pacing systems were implanted in 8 adult mongrel dogs, and continuous rapid right ventricular pacing (RVP, 240 beats/min) was maintained for 2 weeks. The obtained measurements from 2DSTE included global strain rate during early diastole (SRe) and during late diastole (SRa) in the longitudinal (L-SRe, L-SRa), circumferential (C-SRe, C-SRa), and radial directions (R-SRe, R-SRa). Changes in heart morphology were observed by light microscopy and transmission electron microscopy at 2 weeks. The onset of LV diastolic dysfunction with early systolic dysfunction occurred 3 days after RVP initiation. Most of the strain rate imaging indices were altered at 1 or 3 days after RVP onset and continued to worsen until heart failure developed. Light and transmission electron microscopy showed myocardial vacuolar degeneration and mitochondrial swelling in the left ventricular at 2 weeks after RVP onset. Pearson's correlation analysis revealed that parameters of conventional echocardiography and 2DSTE showed moderate correlation with LV pressure parameters, including E/Esep' (r = 0.58, P echocardiography and strain rate imaging could effectively predict LV diastolic dysfunction (area under the curve: E/Esep' 0.78; L-SRe 0.84; E/L-SRe 0.80; R-SRe 0.80). 2DSTE was a sensitive and accurate technique that could be used for predicting LV diastolic dysfunction in canine heart failure model. © 2015, Wiley Periodicals, Inc.

  19. Status of therapeutic gene transfer to treat canine dilated cardiomyopathy in dogs.

    Science.gov (United States)

    Sleeper, Meg M; Bish, Lawrence T; Sweeney, H Lee

    2010-07-01

    Therapeutic gene transfer holds promise as a way to treat dilated cardiomyopathy from any underlying cause because the approach attempts to address metabolic disturbances that occur at the molecular level of the failing heart. Calcium-handling abnormalities and increased rates of apoptosis are abnormalities that occur in many types of heart disease, and gene therapies that target these metabolic defects have proven to be beneficial in numerous rodent models of heart disease. The authors are currently evaluating this approach to treat canine idiopathic dilated cardiomyopathy.

  20. Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals.

    Science.gov (United States)

    Stier, Antoine; Reichert, Sophie; Criscuolo, Francois; Bize, Pierre

    2015-11-01

    Ageing is characterized by a progressive deterioration of multiple physiological and molecular pathways, which impair organismal performance and increase risks of death with advancing age. Hence, ageing studies must identify physiological and molecular pathways that show signs of age-related deterioration, and test their association with the risk of death and longevity. This approach necessitates longitudinal sampling of the same individuals, and therefore requires a minimally invasive sampling technique that provides access to the larger spectrum of physiological and molecular pathways that are putatively associated with ageing. The present paper underlines the interest in using red blood cells (RBCs) as a promising target for longitudinal studies of ageing in vertebrates. RBCs provide valuable information on the following six pathways: cell maintenance and turnover (RBC number, size, and heterogeneity), glucose homeostasis (RBC glycated haemoglobin), oxidative stress parameters, membrane composition and integrity, mitochondrial functioning, and telomere dynamics. The last two pathways are specific to RBCs of non-mammalian species, which possess a nucleus and functional mitochondria. We present the current knowledge about RBCs and age-dependent changes in these pathways in non-model and wild species that are especially suitable to address questions related to ageing using longitudinal studies. We discuss how the different pathways relate with survival and lifespan and give information on their genetic and environmental determinants to appraise their evolutionary potential. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  2. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  3. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  4. Canine Parvovirus: Current Perspective

    OpenAIRE

    Nandi, S.; Kumar, Manoj

    2010-01-01

    Canine parvovirus 2 (CPV-2) has been considered to be an important pathogen of domestic and wild canids and has spread worldwide since its emergence in 1978. It has been reported from Asia, Australia, New Zealand, the Americas and Europe. Two distinct parvoviruses are now known to infect dogs—the pathogenic CPV-2 and CPV-1 or the minute virus of canine (MVC). CPV-2, the causative agent of acute hemorrhagic enteritis and myocarditis in dogs, is one of the most important pathogenic viruses with...

  5. Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Renato A. K. Kalil

    2002-09-01

    Full Text Available OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg, in which 0.5 mL of saline solution (n=1 or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4 were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF instead of EGFP aims at developing gene therapy for ischemic heart disease.

  6. Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

    Science.gov (United States)

    Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

    1996-01-01

    To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

  7. Comparison of Point Placement by Veterinary Professionals with Different Levels of Acupuncture Training in a Canine Cadaver Model.

    Science.gov (United States)

    Yang, Toni; Shmalberg, Justin; Hochman, Lindsay; Miscioscia, Erin; Brumby, Meghan; McKenna, Kelsey; Roth, Amber

    2017-10-01

    Veterinary acupuncture is becoming increasingly implemented for various disease processes, with growing numbers of veterinarians pursuing advanced training to meet the rising demand for this relatively new intervention. Accurate acupoint placement remains challenging, with individual practitioners relying on varying methods of point identification, often compounded by the transpositional nature of points for companion animals. The aim of this study was to assess for differences in acupuncture needle placement of select points between veterinary professionals with three different levels of acupuncture training in an academic teaching environment. Seven participants placed a total of six acupoints on a canine cadaver. Digital radiography was used to document each participant's point placement. Each participant's point location was then compared to a control "correct" point, and the distance between the two points was measured. A significant difference in placement accuracy was identified between the participants when grouped by training level (p = 0.03). These results indicate that veterinary patients receiving acupuncture treatment from veterinarians with different levels of training may subsequently experience varying effects, although further studies are warranted on more specific acupoint description as well as the clinical implications of needle placement accuracy. Copyright © 2017. Published by Elsevier B.V.

  8. High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Science.gov (United States)

    Nishitani, Kohei; Mietus, Zachary; Beck, Christopher A; Ito, Hiromu; Matsuda, Shuichi; Awad, Hani A; Ehrhart, Nicole; Schwarz, Edward M

    2017-01-01

    Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  9. High dose teriparatide (rPTH1-34 therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Directory of Open Access Journals (Sweden)

    Kohei Nishitani

    Full Text Available Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34 effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20 received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1 Placebo (n = 5; daily saline, 2 Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op, or 3 Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op. Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05. These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR on host bone and graft-host junctions (p<0.05. Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05. Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01. In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  10. Effect of laser wavelength and protein solder concentration on acute tissue repair using laser welding: initial results in a canine ureter model.

    Science.gov (United States)

    Wright, E J; Poppas, D P

    1997-01-01

    Successful tissue approximation can be performed using low power laser energy combined with human albumin solder. In vitro studies were undertaken to investigate the acute repair strengths achieved using different laser wavelengths. Furthermore, we evaluated the change in repair strength with that resulted from changes in protein solder concentration. Intraluminal bursting pressure following ureterotomy repair was measured for the following laser wavelengths: 532, 808, 1,320, 2,100, and 10,600 nm. The tissue absorption characteristics of the 808-nm diode and the KTP-532-nm lasers required the addition of the exogenous chromophores indocyanine green and fluorescein, respectively. A 40% human albumin solder was incorporated in the repair of a 1.0-cm longitudinal defect in the canine ureter. Following determination of an optimal welding wavelength, human albumin solder of varying concentrations (25%, 38%, 45%, and 50%) were prepared and tested. The 1,320-nm YAG laser achieved the highest acute bursting pressure and was the most effective in this model. Of the concentrations of albumin tested, 50% human albumin yielded the greatest bursting pressures. We conclude that of the laser wavelengths evaluated, the 1,320-nm YAG achieves the strongest tissue weld in the acute ex vivo dog ureter model. In addition, when this laser system is used, the acute strength of a photothermal weld appears to be directly proportional to the concentration of human albumin solder in the range of 25 to 50%.

  11. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    Science.gov (United States)

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-02-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

  12. Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model

    Directory of Open Access Journals (Sweden)

    Olivia Rodríguez-Morales

    2013-01-01

    Full Text Available The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD. Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP and an amastigote-specific glycoprotein (TcSSP4 were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.

  13. Renal denervation using catheter-based radiofrequency ablation with temperature control: renovascular safety profile and underlying mechanisms in a hypertensive canine model.

    Science.gov (United States)

    Li, Huijie; Yu, Hang; Zeng, Chunyu; Fang, Yuqiang; He, Duofen; Zhang, Xiaoqun; Wen, Chunlan; Yang, Chengming

    2015-01-01

    Renal denervation is a novel method for hypertension treatment. In this study, we aimed to investigate the safety and efficacy of radiofrequency ablation (RFA) at ablation temperatures of 45 °C or 50 °C and its possible mechanisms. A hypertensive canine model was established by abdominal aortic constriction in 20 healthy hybrid dogs. These dogs were then randomly assigned to the treatment and the control groups, with dogs in the treatment group further randomly assigned to receive RFA at ablation temperatures of 45 °C or 50 °C. In the treatment group, RFA was performed at 1 month after modeling; renal angiography was performed at 2 months after ablation. The arterial vessels of the dogs were examined histologically with hematoxylin and eosin staining. Changes in blood pressure in the foreleg and whole-body norepinephrine spillover rate were also assessed. No arterial stenosis, dissection, thrombosis or other abnormalities were detected in the treated vessels by renal angiography, yet histology results showed minimal to mild renal arterial injury. Renal denervation resulted in a marked decrease in the whole-body norepinephrine spillover rate (p 0.05). Renal denervation can be performed without acute major adverse events, using catheter-based RFA with temperature control. The procedure was feasible in reducing blood pressure by at least partially inhibiting sympathetic drive and systemic sympathetic outflow.

  14. Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

    Science.gov (United States)

    Tabereaux, Paul B; Walcott, Greg P; Rogers, Jack M; Kim, Jong; Dosdall, Derek J; Robertson, Peter G; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E

    2007-09-04

    The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo. Six canine hearts were isolated, and the left main coronary artery was cannulated and perfused. The left ventricular cavity was exposed, which allowed direct endocardial mapping of the anterior papillary muscle insertion. Nonperfused VF was induced, and 6 segments of data, each 5 seconds long, were analyzed during 10 minutes of VF. During 36 segments of data that were analyzed, 1018 PF or focal wave fronts of activation were identified. In 534 wave fronts, activation was mapped propagating from working ventricular myocardium to PF. In 142 wave fronts, activation was mapped propagating from PF to working ventricular myocardium. In 342 wave fronts, activation was mapped arising focally. More than 1 of these 3 patterns could occur in the same wave front. PFs are highly active throughout the first 10 minutes of VF. In addition to retrograde propagation from the working ventricular myocardium to PFs, antegrade propagation occurs from PFs to working ventricular myocardium, which suggests PFs are important in VF maintenance. Prior plunge needle recordings in dogs indicate activation propagates from the endocardium toward the epicardium after 1 minute of VF, which suggests that focal sites on the endocardium may represent foci and not breakthrough. If so, in addition to reentry, abnormal automaticity or triggered activity may also occur during VF.

  15. Radioactive metallic stent for palliative treatment of esopageal cancer using Ho-166: an experimental study in canine model

    Energy Technology Data Exchange (ETDEWEB)

    Won, J. H.; Lee, J. D. [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of); Wang, H. J.; Lim, H. E.; Park, C. H. [College of Medicine, Ajou Univ., Inchon (Korea, Republic of); Park, K. B. [KAERI, Taejon (Korea, Republic of)

    1999-07-01

    Self-expandable metallic stents are widely used for palliative treatment of esophageal cancer, however, tumor overgrowth and short survaval limit its long-term effect. The purpose of this study is to evaluate tissue response of the radiation effect in normal canine esophagus whether metallic stents coated with radioactive H-166 is effective for patients survival and preservation of stent patency longer than stents without radioactive materials. Ho-166 was incorporated within polyurethan (50{mu}) and coated over the outer surface of self-expandable metallic stents. Metallic stents with radioactivity of 4.0-7.8mCi (Group A), 1.0-1.8 mCi (Group B) and 0.5-0.7mCi (Group C) were placed in normal mid-esophagus in twelve dogs (Group A), five (Group B) and another five dogs (Group C) respectively, and the stents were tightly anchored by surgery to prevent migration. Estimated radiation dose was 6-70 Gy in Group C. Fluoroscopy confirmed stents in esophagus without migration for at least two days. The dogs were sacrified at two or three months later and histopathologic examinations were performed. In group A, mid-esophagus stricture, mucosal ulceration were found in all specimens. Severe fibrosis and degeneration of muscular propria, upper one half were found in three and complete fibrosis of esophageal wall, however, esophageal perforation was found but muscular layer was intact. In group C, no histological changes was demonstrated in three but submucosal inflammation with intact mucosa in two. In therapeutic dose level (group B), radioactive metallic stent showed radiation effect within esophageal wall without complication which might give additional palliative effect in malignant espohageal stricture.

  16. Infusing BSCS 5E Instructional Model with Multimedia: A Promising Approach to Develop 21st Century Skills

    Science.gov (United States)

    Senan, Divya C.

    2013-01-01

    The full promise of class room learning is dependent on its ability to incorporate 21st century skills in its instructional design, delivery and implementation. In this increasingly competitive global economy, it is not enough for students to acquire subject-level mastery alone. Skills like creative thinking, problem-solving, communication and…

  17. TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, T; Boone, J [University of California Davis School of Medicine, Sacramento, CA (United States); Kent, M; Wisner, E [University of California Davis School of Veterinary Medicine, Davis, CA (United States); Fujita, Y [Tokai University, Isehara (Japan)

    2015-06-15

    Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtraction image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R{sup 2}=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral

  18. The experimental study of 32P and diallyl trisulfide coating stent for inhibiting neointimal hyperplasia in a canine model of coronary restenosis

    International Nuclear Information System (INIS)

    Xu Shanghua; Jiang Hong; Li Gengshan; Jiang Xuejun; Li Xiaoyan; Chen Yuanxiu; Wang Hairong; Wu Kegui; Nie Xiaomin

    2004-01-01

    Objective: To assesses the efficiency of 32 P and diallyl trisulfide (DT)-coated coronary stents on neointimal proliferation in a canine model of restenosis. Methods: 32 P (740 kBq/stent), DT (210 μg/stent) alone and jointly coated stents were deployed with mild oversizing in both the left circumflex coronary artery (LCX) and the left anterior descending coronary artery (LAD) of 10 dogs. The implantation of protein-coated stents was used as the control. The therapeutic effect was assessed 6 months after the intervention. The dogs were sacrificed and the vessels were excised. For morphologic examinations the tissue sections were stained with HE and Van Gieson. Results: Compared with the control stents, the neointimal area reduced in stents coated with 32 P, DT alone and 32 P+DT [ 32 P: (2.63±0.48) mm 2 , DT: (2.50±0.49) mm 2 , 32 P+DT: (1.42±0.41) mm 2 vs control group: (4.87±0. 80) mm 2 , P=0.001]. 32 P+DT was more effective than either of them alone for reducing the neointimal area (P≤0.005). Both jointly and alone coated stents of 32 P, DT decreased the percent area stenosis [ 32 P: (32.48±4.79)%, DT: (30.04±5.43)%, 32 P+DT: (17.21±4.05)% vs control group: (54.62±6.82)%, P 32 P+DT group compared with 32 P or DT-coated stents group (P≤0.001). Angiographic restenosis (diameter stenosis) was lighter in stents coated with 32 P, DT and 32 P+DT compared with control stents (P 32 P+DT was more effective than 32 P or DT alone for reducing diameter stenosis (P≤0.005). No evidence of 'edge effect' was seen in adjacent, nonstented coronary segments. Conclusion: Coronary stents coated with 32 P plus DT produced a significantly reduced neointimal hyperplasia and restenosis rate in the canine LCX and LAD 6 months after stents implantation

  19. TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

    International Nuclear Information System (INIS)

    Yamamoto, T; Boone, J; Kent, M; Wisner, E; Fujita, Y

    2015-01-01

    Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtraction image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R"2=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral

  20. [1-11C]octanoate as a PET tracer for studying ischemic stroke. Evaluation in a canine model of thromboembolic stroke with positron emission tomography

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Minematsu, Kazuo

    2000-01-01

    Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after β-oxidation. Consequently, [1- 11 C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1- 11 C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1- 11 C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2, 3, 5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1- 11 C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1- 11 C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1- 11 C]octanoate relative to CBF takes place in these regions. In conclusion, [1- 11 C]octanoate accumulated in ischemic but vital regions, indicating that [1- 11 C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. (author)

  1. Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Toedebusch, Christine M; Snyder, John C; Jones, Maria R; Garcia, Virginia B; Johnson, Gayle C; Villalón, Eric L; Coates, Joan R; Garcia, Michael L

    2018-04-01

    Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model.

    Science.gov (United States)

    Freeman, John; Chen, Aaron; Weinberg, Roy J; Okada, Tamuru; Chen, Changyi; Lin, Peter H

    2018-05-01

    Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P  0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

    Science.gov (United States)

    Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

    2016-02-01

    Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

  4. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Martin K Childers

    2012-01-01

    Full Text Available Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD. Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD. Young (6 week-old GRMD dogs were treated daily with either C101 (17mg/kg twice daily oral dose, n=9 or placebo (vehicle only, n=7 for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every two weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors. C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.

  5. Absolute quantitation of myocardial blood flow with {sup 201}Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

    Energy Technology Data Exchange (ETDEWEB)

    Iida, Hidehiro; Kim, Kyeong-Min; Nakazawa, Mayumi; Sohlberg, Antti; Zeniya, Tsutomu; Hayashi, Takuya; Watabe, Hiroshi [National Cardiovascular Center Research Institute, Department of Investigative Radiology, Suita City, Osaka (Japan); Eberl, Stefan [National Cardiovascular Center Research Institute, Department of Investigative Radiology, Suita City, Osaka (Japan); Royal Prince Alfred Hospital, PET and Nuclear Medicine Department, Camperdown, NSW (Australia); Tamura, Yoshikazu [Akita Kumiai General Hospital, Department of Cardiology, Akita City (Japan); Ono, Yukihiko [Akita Research Institute of Brain, Akita City (Japan)

    2008-05-15

    {sup 201}Tl has been extensively used for myocardial perfusion and viability assessment. Unlike {sup 99m}Tc-labelled agents, such as {sup 99m}Tc-sestamibi and {sup 99m}Tc-tetrofosmine, the regional concentration of {sup 201}Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of {sup 201}Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of {sup 201}Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K{sub 1}) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF{sub SPECT}) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF{sub MS}) (MBF{sub SPECT} = -0.067 + 1.042 x MBF{sub MS}, p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using {sup 201}Tl and dynamic SPECT. (orig.)

  6. The Comparative Diagnostic Features of Canine and Human Lymphoma

    Directory of Open Access Journals (Sweden)

    Davis M. Seelig

    2016-06-01

    Full Text Available The non-Hodgkin lymphomas (NHLs are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  7. The Comparative Diagnostic Features of Canine and Human Lymphoma.

    Science.gov (United States)

    Seelig, Davis M; Avery, Anne C; Ehrhart, E J; Linden, Michael A

    2016-06-01

    The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  8. Canine parvovirus: current perspective.

    Science.gov (United States)

    Nandi, S; Kumar, Manoj

    2010-06-01

    Canine parvovirus 2 (CPV-2) has been considered to be an important pathogen of domestic and wild canids and has spread worldwide since its emergence in 1978. It has been reported from Asia, Australia, New Zealand, the Americas and Europe. Two distinct parvoviruses are now known to infect dogs-the pathogenic CPV-2 and CPV-1 or the minute virus of canine (MVC). CPV-2, the causative agent of acute hemorrhagic enteritis and myocarditis in dogs, is one of the most important pathogenic viruses with high morbidity (100%) and frequent mortality up to 10% in adult dogs and 91% in pups. The disease condition has been complicated further due to emergence of a number of variants namely CPV-2a, CPV-2b and CPV-2c over the years and involvement of domestic and wild canines. There are a number of different serological and molecular tests available for prompt, specific and accurate diagnosis of the disease. Further, both live attenuated and inactivated vaccines are available to control the disease in animals. Besides, new generation vaccines namely recombinant vaccine, peptide vaccine and DNA vaccine are in different stages of development and offer hope for better management of the disease in canines. However, new generation vaccines have not been issued license to be used in the field condition. Again, the presence of maternal antibodies often interferes with the active immunization with live attenuated vaccine and there always exists a window of susceptibility in spite of following proper immunization regimen. Lastly, judicious use of the vaccines in pet dogs, stray dogs and wild canids keeping in mind the new variants of the CPV-2 along with the proper sanitation and disinfection practices must be implemented for the successful control the disease.

  9. Comparison of a novel bone-tendon allograft with a human dermis-derived patch for repair of chronic large rotator cuff tears using a canine model.

    Science.gov (United States)

    Smith, Matthew J; Cook, James L; Kuroki, Keiichi; Jayabalan, Prakash S; Cook, Cristi R; Pfeiffer, Ferris M; Waters, Nicole P

    2012-02-01

    This study tested a bone-tendon allograft versus human dermis patch for reconstructing chronic rotator cuff repair by use of a canine model. Mature research dogs (N = 15) were used. Radiopaque wire was placed in the infraspinatus tendon (IST) before its transection. Three weeks later, radiographs showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D), direct repair of IST to bone with a suture bridge and human dermis patch augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures included lameness grading, radiographs, and ultrasonographic assessment. Dogs were killed 6 months after surgery and both shoulders assessed biomechanically and histologically. BT dogs were significantly (P = .01) less lame than the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle integrity compared with D and GJ dogs. Biomechanical testing showed that the D group had significantly (P = .05) more elongation than the other groups whereas BT had stiffness and elongation characteristics that most closely matched normal controls. Radiographically, D and GJ dogs showed significantly more retraction than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor tendon-bone integration. BT dogs showed complete incorporation of allograft bone into host bone, normal bone-tendon junctions, and well-integrated allograft tendon. The bone-tendon allograft technique re-establishes a functional IST bone-tendon-muscle unit and maintains integrity of repair in this model. Clinical trials using this bone-tendon allograft technique are warranted. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  10. Radiation, chemotherapy and surgery for canine osteosarcoma

    International Nuclear Information System (INIS)

    Powers, B.E.; Withrow, S.J.; La Rue, S.M.; Straw, R.C.; Gillette, E.L.

    1987-01-01

    Spontaneous canine osteosarcomas is an excellent model for of human osterosarcoma. Twenty dogs with obsteorsarcoma were treated with intravenous or intraarterial cisplatin with or without radiation therapy. This treatment was given 3 weeks prior to limb sparing surgery involving excision of the tumor and allograft replacement. The excised tumor specimen was examined for complete removal and percentage of necrotic tumor measured by planimetry. Intraveneous and intraarterial cisplatin and radiation methods were compared. Data discussing rate of disease development and recurrences is given

  11. Bilateral supernumerary primary maxillary canines

    Directory of Open Access Journals (Sweden)

    Santanu Mukhopadhyay

    2018-01-01

    Full Text Available Supernumerary teeth are more common in the permanent than in primary dentition. In the primary dentition, the anomaly is most frequently observed in the maxillary lateral incisor region, followed by the maxillary midline where they are termed as mesiodens. Supernumerary teeth in the primary canine region are rare. This paper describes a rare case of nonsyndromic supernumerary primary maxillary canine distributed bilaterally in a 4-year-old boy. Both the supernumeraries resembled size and shape of normal primary canine. The right supplemental canine is high labially placed, whereas the left one is seen normally aligned in the dental arch distal to lateral incisor. One of the most significant sequelae of primary supernumerary teeth is their duplication in the permanent series. Radiographic examination of supernumerary primary canine did not indicate any such anomaly in the permanent dentition. The patient was kept under observation.

  12. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  13. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome

    2011-05-01

    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  14. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    International Nuclear Information System (INIS)

    Hedan, Benoit; Thomas, Rachael; Motsinger-Reif, Alison; Abadie, Jerome; Andre, Catherine; Cullen, John; Breen, Matthew

    2011-01-01

    Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards

  15. Canine hypothyroidism. A diagnostic challenge?

    International Nuclear Information System (INIS)

    Boretti, Felicitos; Reusch, C.E.

    2010-01-01

    Hypothyroidism is one of the most common endocrinopathies in dogs. Clinical symptoms and hematological and biochemical parameters lead to a first suspicion. To confirm diagnosis can be challenging, however. Determination of total serum T4 concentration is accepted as the primary screening test for the disease, and low serum T4 concentrations are intuitively suggestive of hypothyroidism. However it is well known that low T4 concentrations are frequently encountered in euthyroid dogs with various nonthyroidal diseases and in dogs receiving certain pharmacologic agents. Since assessment of endogenous TSH (canine TSH) using current canine TSH assays shows normal values in a high percentage of hypothyroid dogs (up to 40%), its diagnostic value is only limited. The TSH-stimulation test can still be recognized as the gold standard for the diagnosis of hypothyroidism in dogs. Determination of circulating T4 concentration before and 6 hours after the administration of exogenous TSH (recombinant human TSH, Thyrogen registered ) provides an assessment of the functional reserve capacity of the thyroid gland with minimal change in post-TSH T4 concentration, compared with the basal concentration, expected in dogs with hypothyroidism. Also this test can be influenced by nonthyroidal illness and by medications known to affect thyroid function. This suppressing influence seems to be less pronounced using a higher dose of TSH. Therefore, to improve the discriminatory power of the TSH stimulation test to differentiate between euthyroid-sick and primary hypothyroidism, the higher dose should be used in cases in which testing cannot be delayed. More recently, ultrasonography and scintigraphy have been used for the diagnosis of primary hypothyroidism. Using ultrasonography, a sensitivity of 98% was reported if size and echogenicity of the gland were combined. However, specificity was as low as 77%. and care must be taken when measuring the gland because of a relatively high

  16. In a Canine Pneumonia Model of Exchange-Transfusion, Altering the Age but Not the Volume of Older Red Blood Cells Markedly Alters Outcome

    Science.gov (United States)

    Cortés-Puch, Irene; Remy, Kenneth E.; Solomon, Steven B.; Sun, Junfeng; Wang, Dong; Al-Hamad, Mariam; Kelly, Seth M.; Sinchar, Derek; Bellavia, Landon; Kanias, Tamir; Popovsky, Mark A.; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles

    2015-01-01

    Background Massive exchange-transfusion of 42-day-old red blood cells (RBCs) in a canine model of S. aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-transferrin bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs. Study Design and Methods Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n=36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days) (n=40). Results All volumes transfused (5-80 mL/kg) of 42-day-old RBCs, resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg of RBCs stored for 14, 21, 28 and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates. Conclusions Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance. PMID:26469998

  17. Detection of viable myocardium in canine model with myocardial ischemia and ischemia-reperfusion by 125I-BMIPP: relation to regional blood flow

    International Nuclear Information System (INIS)

    Huang Gang; Zhao Huiyang; Shen Xuedong; Li Qing; Yuan Jimin; Zhu Cuiying

    1999-01-01

    Objective: The effects of BMIPP (β-methyl-iodophenyl pentadecanoic acid) on detecting viable myocardium and the relation between regional blood flow and the uptake of BMIPP were evaluated in canine model of myocardial ischemia and ischemia-reperfusion. Methods: 12 open-chest dogs under anesthesia were divided into two groups. Group I (ischemia group) had left circumflex coronary arterial occlusion for 2 h and group II (ischemia-reperfusion group) was occluded for 1 h and followed by 2 h reperfusion. Myocardial blood flow was measured with 99 Tc m -microspheres. 30 min after intravenous injection of 125 I-BMIPP and 99 Tc m -microspheres, the heart was excised rapidly and stained with Evans blue and NBT. Tissue samples (divided into approximately 1 g) of left ventricle were obtained, weighed and counted for 125 I and 99 Tc m . Regional blood flow and the uptake of BMIPP were expressed as percentages of average values in non-ischemic myocardium (two to three tissue samples) from the normal myocardium. Results: In ischemic myocardium (NBT positive samples), the uptake of BMIPP was relatively higher compared with regional blood flow [(67 +- 23)% vs (42 +- 19)%, P 0.05]. In ischemia-reperfusion group, regional blood flow was increased in ischemic and necrotic tissues, but the uptake of BMIPP was not enhanced with the increasing blood flow. Conclusions: BMIPP uptake seems to provide metabolic information independent of regional blood flow. The mismatching between regional blood flow and BMIPP uptake may indicate myocardial viability in the regions of hypoperfusion and the uptake of BMIPP in ischemic myocardium was related to existence of cellular metabolism

  18. Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.

    Directory of Open Access Journals (Sweden)

    Junko Shibayama

    Full Text Available Deterioration of ventricular fibrillation (VF into asystole or severe bradycardia (electrical failure heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia.Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys, while 5/9 hearts maintained VF for at least 19.7 min (late-asys. As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05. Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05.High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

  19. Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.

    Science.gov (United States)

    Puram, Sidharth V; Chow, Harold; Wu, Che-Wei; Heaton, James T; Kamani, Dipti; Gorti, Gautham; Chiang, Feng Yu; Dionigi, Gianlorenzo; Barczynski, Marcin; Schneider, Rick; Dralle, Henning; Lorenz, Kerstin; Randolph, Gregory W

    2016-12-01

    Injury to the recurrent laryngeal nerve (RLN) is a dreaded complication of endocrine surgery. Intraoperative neural monitoring (IONM) has been increasingly utilized to assess the functional status of the RLN. Although the posterior cricoarytenoid muscle (PCA) is innervated by the RLN as the abductor of the larynx, PCA electromyography (EMG) is infrequently recorded during IONM and PCA activity after RLN compressive injury remains poorly characterized. Single-subject prospective animal study. We employed a canine model to identify postcricoid EMG correlates of postoperative vocal cord paralysis (VCP). Postcricoid electrode recordings were obtained before and after compressive RLN injury associated with VCP. Normative postcricoid recordings revealed mean amplitude of 1288 microvolt (μV) and latency of 8.2 millisecond (ms) with maximum (1 milliamp [mA]) vagal stimulation, and mean amplitude of 1807 μV and latency of 3.5 ms with maximum (1 mA) RLN stimulation. Following injury that was associated with VCP, there was 62.1% decrement in postcricoid EMG amplitude with maximum vagal stimulation and 80% decrement with maximum RLN stimulation. Threshold stimulation of the vagus increased by 23%, and there was a corresponding 42% decrease in amplitude. For RLN stimulation, latency increased by 17.3% following injury, whereas threshold stimulation increased by 61% with 35.5% decrement in EMG amplitude. Thus, if RLN amplitude decreases by ≥ 80%, with absolute amplitude of ≤ 300 μV or less and latency increase of ≥ 10%, RLN injury is likely associated with VCP. Our results predict postoperative VCP based on postcricoid electromyographic IONM and may guide surgical decision making. NA Laryngoscope, 126:2744-2751, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Comparison of diamond-like carbon-coated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model

    Science.gov (United States)

    Kim, J H; Shin, J H; Shin, D H; Moon, M-W; Park, K; Kim, T-H; Shin, K M; Won, Y H; Han, D K; Lee, K-R

    2011-01-01

    Objective Neointimal hyperplasia is a major complication of endovascular stent placement with consequent in-stent restenosis or occlusion. Improvements in the biocompatibility of stent designs could reduce stent-associated thrombosis and in-stent restenosis. We hypothesised that the use of a diamond-like carbon (DLC)-coated nitinol stent or a polyethylene glycol (PEG)-DLC-coated nitinol stent could reduce the formation of neointimal hyperplasia, thereby improving stent patency with improved biocompatibility. Methods A total of 24 stents were implanted, under general anaesthesia, into the iliac arteries of six dogs (four stents in each dog) using the carotid artery approach. The experimental study dogs were divided into three groups: the uncoated nitinol stent group (n = 8), the DLC-nitinol stent group (n = 8) and the PEG-DLC-nitinol stent group (n = 8). Results The mean percentage of neointimal hyperplasia was significantly less in the DLC-nitinol stent group (26.7±7.6%) than in the nitinol stent group (40.0±20.3%) (p = 0.021). However, the mean percentage of neointimal hyperplasia was significantly greater in the PEG-DLC-nitinol stent group (58.7±24.7%) than in the nitinol stent group (40.0±20.3%) (p = 0.01). Conclusion Our findings indicate that DLC-coated nitinol stents might induce less neointimal hyperplasia than conventional nitinol stents following implantation in a canine iliac artery model; however, the DLC-coated nitinol stent surface when reformed with PEG induces more neointimal hyperplasia than either a conventional or DLC-coated nitinol stent. PMID:21325363

  1. Enhancement of abdominal wall defect repair using allogenic platelet-rich plasma with commercial polyester/cotton fabric (Damour) in a canine model

    Science.gov (United States)

    ABOUELNASR, Khaled; HAMED, Mohamed; LASHEN, Samah; EL-ADL, Mohamed; ELTAYSH, Rasha; TAGAWA, Michihito

    2017-01-01

    Platelet-rich plasma (PRP) has an important role in musculoskeletal surgery; however, it has been underutilized for accelerating the healing of abdominal wall defects in veterinary practice. Therefore, the aim of this study was to evaluate the use of commercial polyester/cotton fabric (Damour) as a new composite mesh for the repair of experimentally induced abdominal wall defects in canine models, and to investigate the possible role of PRP for improving such repair and reducing allied complications. For this purpose, abdominal wall defects were created in 24 healthy mongrel dogs and then repaired with mesh alone (control group) or mesh and allogenic PRP (PRP group). Dogs were euthanized after 2 or 4 months for gross examination of implantation site, detection of adhesion score and hernia recurrence. Moreover, tissue samples were collected for histological and gene expression analyses for neovascularization, collagen formation and tissue incorporation. Hernia recurrence was not recorded in PRP-treated dogs that also displayed significantly more neovascularization and less severe adhesion to the underlings (1.08 ± 0.51) in comparison to control group (2.08 ± 0.99). Histological and molecular evaluation confirmed the gross findings that collagen deposition, new vessel formation, and overexpression of angiogenic and myofibroplastic genes (COL1α1, COL3α1, VEGF and TGFβ1) were observed more frequently in the PRP group, at both time points. In conclusion, we found that addition of allogenic PRP to Damour mesh enhanced neovessel formation, and increased tissue deposition and incorporation, with subsequent reduction of peritoneal adhesion and recurrence rate. PMID:28603214

  2. Comparison of the virulence of three H3N2 canine influenza virus isolates from Korea and China in mouse and Guinea pig models.

    Science.gov (United States)

    Xie, Xing; Na, Woonsung; Kang, Aram; Yeom, Minjoo; Yuk, Heejun; Moon, Hyoungjoon; Kim, Sung-Jae; Kim, Hyun-Woo; Kim, Jeong-Ki; Pang, Maoda; Wang, Yongshan; Liu, Yongjie; Song, Daesub

    2018-05-02

    Avian-origin H3N2 canine influenza virus (CIV) has been the most common subtype in Korea and China since 2007. Here, we compared the pathogenicity and transmissibility of three H3N2 CIV strains [Chinese CIV (JS/10), Korean CIV (KR/07), and Korean recombinant CIV between the classic H3N2 CIV and the pandemic H1N1 virus (MV/12)] in BALB/c mouse and guinea pig models. The pandemic H1N1 (CA/09) strain served as the control. BALB/c mice infected with H1N1 had high mortality and obvious body weight loss, whereas no overt disease symptoms were observed in mice inoculated with H3N2 CIV strains. The viral titers were higher in the group MV/12 than those in groups JS/10 and KR/07, while the mice infected with JS/10 showed higher viral titers in all tissues (except for the lung) than the mice infected with KR/07. The data obtained in guinea pigs also demonstrated that group MV/12 presented the highest loads in most of the tissues, followed by group JS/10 and KR/07. Also, direct contact transmissions of all the three CIV strains could be observed in guinea pigs, and for the inoculated and the contact groups, the viral titer of group MV/12 and KR/07 was higher than that of group JS/10 in nasal swabs. These findings indicated that the matrix (M) gene obtained from the pandemic H1N1 may enhance viral replication of classic H3N2 CIV; JS/10 has stronger viral replication ability in tissues as compared to KR/07, whereas KR/07 infected guinea pigs have more viral shedding than JS/10 infected guinea pigs. There exists a discrepancy in pathobiology among CIV isolates. Reverse genetics regarding the genomes of CIV isolates will be helpful to further explain the virus characteristics.

  3. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    International Nuclear Information System (INIS)

    Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2013-01-01

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P 3 H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM

  4. The short and long term effects of intraoperative electron beam radiotherapy (IORT) on thoracic organs after pneumonectomy an experimental study in the canine model

    International Nuclear Information System (INIS)

    Boer, Willem J. de; Mehta, Dinesh M.; Timens, Wim; Hoekstra, Harald J.

    1999-01-01

    Purpose: The tolerance of mediastinal structures and thoracic organs to intraoperative radiotherapy (IORT) was investigated in the canine model. Methods and Materials: Twenty-two adult beagles divided into three groups were subjected to a left pneumonectomy and IORT (10 MeV electrons) at doses of 20 Gy (n = 9), 25 Gy (n = 4), or 30 Gy (n = 9). Intraoperative electron beam radiotherapy was delivered through a 5 cm circular lucite cone encompassing a mediastinal field including the bronchial stump, aorta, esophagus, heart, phrenic nerve, contralateral hilar structures, and lung. Clinical monitoring was performed with regular chest X-ray, ECG, bronchoscopy, esofagoscopy, and fluoroscopy. From the different treatment dose groups, dogs were electively sacrificed at 1.5, 6, 12, and 72 months with complete autopsies. Results: There was no bronchial stump dehiscence or acute morbidity. Four dogs developed radiation induced esophagitis (18%), one in the 20 Gy IORT group (11%) and three in the 30 Gy IORT group (33%). There were six IORT related mortalities (27.5%), one esophagoaortic fistula (4.5%) and five bronchovascular fistulas (23%): two in the 20 Gy IORT group (22%), two in the 25 Gy IORT group (50%) and two in the 30 Gy IORT group (22%). Histopathological findings in uncomplicated follow-up showed marked myointimal fibrosis in the muscular arteries, submucosal fibrosis of the esophagus, and interstitial fibrosis of bronchial and lung tissue, especially in the higher dose group. Conclusion: The mediastinal vascular, bronchial and esophageal structures are relatively sensitive to doses > 20Gy IORT. The IORT related morbidity found in this study may be lower when the current clinically used IORT doses of 10-15 Gy are applied. Further clinical application of IORT in the future treatment strategies for resectable non small cell lung cancer may be worthwhile to investigate

  5. Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

    Science.gov (United States)

    Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

    2015-01-01

    Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

  6. Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

    2017-02-01

    An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Das K

    2017-04-01

    Full Text Available Kinsuk Das,1 AP Madhusoodan,1 Bhabesh Mili,1 Ajay Kumar,2 AC Saxena,3 Kuldeep Kumar,1 Mihir Sarkar,1 Praveen Singh,4 Sameer Srivastava,5 Sadhan Bag1 1Division of Physiology and Climatology, 2Biochemistry and Food Science Section, 3Division of Surgery, 4Biophysics, Electron Microscopy and Instrumentation Section, 5Division of Veterinary Biotechnology, Indian Council of Agricultural Research – Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India Abstract: In the field of regenerative medicine, numerous potential applications of mesenchymal stem cells (MSCs can be envisaged, due to their ability to differentiate into a range of tissues on the basis of the substrate on which they grow. With the advances in nanotechnology, carbon nanotubes (CNTs have been widely explored for use as cell culture substrate in tissue engineering applications. In this study, canine bone marrow-derived MSCs were considered as the cellular model for an in vitro study to elucidate the collective cellular processes, using three different varieties of thin films of functionalized carbon nanotubes (COOH-single-walled CNTs [SWCNTs], COOH-multiwalled CNTs [MWCNTs] and polyethylene glycol [PEG]-SWCNTs, which were spray dried onto preheated cover slips. Cells spread out better on the CNT films, resulting in higher cell surface area and occurrence of filopodia, with parallel orientation of stress fiber bundles. Canine MSCs proliferated at a slower rate on all types of CNT substrates compared to the control, but no decline in cell number was noticed during the study period. Expression of apoptosis-associated genes decreased on the CNT substrates as time progressed. On flow cytometry after AnnexinV-fluorescein isothiocyanate/propidium iodide (PI staining, total number of apoptotic and necrotic cells remained lower in COOH-functionalized films compared to PEG-functionalized ones. Collectively, these results indicate that COOH-MWCNT substrate provided an

  8. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

    Science.gov (United States)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine

    2014-11-01

    The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however

  9. Elicited vs. voluntary promises

    NARCIS (Netherlands)

    Ismayilov, H.; Potters, Jan

    2017-01-01

    We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost

  10. Molecular characterization of the canine HMGB1.

    Science.gov (United States)

    Murua Escobar, H; Meyer, B; Richter, A; Becker, K; Flohr, A M; Bullerdiek, J; Nolte, I

    2003-01-01

    Due to the close similarities of numerous canine diseases to their human counterparts, the dog could join the mouse as the species of choice to unravel the genetic background of complex diseases as e.g. cancer and metabolic diseases. Accordingly, the role of the dog as a model for therapeutic approaches is strongly increasing. However, prerequisite for such studies is the characterization of the corresponding canine genes. Recently, the human high mobility group protein B1 (HMGB1) has attracted considerable interest of oncologists because of what is called its "double life". Besides its function as an architectural transcription factor HMGB1 can also be secreted by certain cells and then acts as a ligand for the receptor for advanced glycation end products (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways, such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1 in inflammation and tumor metastasis. These results make HMGB1 a very interesting target for therapeutic studies done in model organisms like the dog. In this study we characterized the molecular structure of the canine HMGB1 gene on genomic and cDNA levels, its predicted protein, the gene locus and a basic expression pattern. Copyright 2003 S. Karger AG, Basel

  11. Photons, photosynthesis, and high-performance computing: challenges, progress, and promise of modeling metabolism in green algae

    International Nuclear Information System (INIS)

    Chang, C H; Graf, P; Alber, D M; Kim, K; Murray, G; Posewitz, M; Seibert, M

    2008-01-01

    The complexity associated with biological metabolism considered at a kinetic level presents a challenge to quantitative modeling. In particular, the relatively sparse knowledge of parameters for enzymes with known kinetic responses is problematic. The possible space of these parameters is of high-dimension, and sampling of such a space typifies a combinatorial explosion of possible dynamic states. However, with sufficient quantitative transcriptomics, proteomics, and metabolomics data at hand, these challenges could be met by high-performance software with sampling, fitting, and optimization capabilities. With this in mind, we present the High-Performance Systems Biology Toolkit HiPer SBTK, an evolving software package to simulate, fit, and optimize metabolite concentrations and fluxes within the space of rate and binding parameters associated with detailed enzyme kinetic models. We present our chosen modeling paradigm for the formulation of metabolic pathway models, the means to address the challenge of representing such models in a precise and persistent fashion using the standardized Systems Biology Markup Language, and our second-generation model of H2-associated Chlamydomonas metabolism. Processing of such models for hierarchically parallelized simulation and optimization, job specification by the user through a GUI interface, software capabilities and initial scaling data, and the mapping of the computation to biological questions is also discussed. Moreover, we present near-term future software and model development goals

  12. Correlation between intravoxel incoherent motion magnetic resonance imaging derived metrics and serum soluble CD40 ligand level in an embolic canine stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiao Quan; Wu, Chen Jiang; Lu, Shan Shan; Gao, Qian Qian; Zu, Qing Quan; Liu, Xing Long; Shi, Hai Bin; Liu, Sheng [Dept. of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2017-09-15

    To determine the relationship between intravoxel incoherent motion (IVIM) imaging derived quantitative metrics and serum soluble CD40 ligand (sCD40L) level in an embolic canine stroke model. A middle cerebral artery occlusion model was established in 24 beagle dogs. Experimental dogs were divided into low- and high-sCD40L group according to serum sCD40L level at 4.5 hours after establishing the model. IVIM imaging was scanned at 4.5 hours after model establishment using 10 b values ranging from 0 to 900 s/mm{sup 2}. Quantitative metrics diffusion coefficient (D), pseudodiffusion coefficient (D{sup *}), and perfusion fraction (f) of ischemic lesions were calculated. Quantitative metrics of ischemic lesions were normalized by contralateral hemisphere using the following formula: normalized D = D{sub stroke} / D{sub contralateral}. Differences in IVIM metrics between the low- and high-sCD40L groups were compared using t test. Pearson's correlation analyses were performed to determine the relationship between IVIM metrics and serum sCD40L level. The high-sCD40L group showed significantly lower f and normalized f values than the low-sCD40L group (f, p < 0.001; normalized f, p < 0.001). There was no significant difference in D{sup *}, normalized D{sup *}, D, or normalized D value between the two groups (All p > 0.05). Both f and normalized f values were negatively correlated with serum sCD40L level (f, r = −0.789, p < 0.001; normalized f, r = −0.823, p < 0.001). However, serum sCD40L level had no significant correlation with D{sup *}, normalized D{sup *}, D, or normalized D (All p > 0.05). The f value derived from IVIM imaging was negatively correlated with serum sCD40L level. f value might serve as a potential imaging biomarker to assess the formation of microvascular thrombosis in hyperacute period of ischemic stroke.

  13. The Effects of Orthodontic Forces during Canine Retraction Using Self-ligating Brackets on Gingival Crevicular Fluid Enzyme Activity, Canine Movement and Root Resorption

    International Nuclear Information System (INIS)

    Rohaya Megat Abdul Wahab; Albira Sintian; Zaidah Zainal Arifin; Zaidah Zainal Ariffin; Shahrul Hisham Zainal Ariffin

    2015-01-01

    Alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and aspartate aminotransferase (AST) activities were studied as bio markers of canine movement. Root resorption was also evaluated in canines subjected to the orthodontic forces. Nineteen subjects randomly received 100 and 150 g force using self-ligating brackets (SLB) either on the right or left site of maxillary arch. Gingival crevicular fluid samples were collected at distal sites of canines for five consecutive weeks. The activities of ALP, TRAP and AST were assayed and measured spectrophotometrically. Canine movement was measured for five consecutive weeks while root resorption was monitored at baseline, week 0 and week 5 using periapical radiographs. In 100 g group, TRAP activity significantly increased in week 3-5 when compared to TRAP baseline activity. However, ALP and AST activities slightly increased. In 150 g group, ALP and TRAP activities slightly increased when compared with their baseline activities. However, AST significantly increased in week 5. Canine movement and root resorption were not significantly different (p<0.05) in both groups. A force of 100 and 150 g slightly increased the bone modeling process and resulted in similar canine movement and root resorption. Therefore, 100 g force could be an optimum force for canine retraction and is preferable (compared with 150 g force) in canine retraction using SLB. (author)

  14. THE REDUCED CANINE PANCREAS TO STUDY THE EFFECTS OF INTRAOPERATIVE RADIOTHERAPY

    NARCIS (Netherlands)

    HEIJMANS, HJ; MEHTA, D; KLEIBEUKER, JH; SLUITER, WJ; HOEKSTRA, HJ

    1993-01-01

    A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of

  15. Nd : YAG surgical laser effects in canine prostate tissue: temperature and damage distribution

    NARCIS (Netherlands)

    van Nimwegen, S. A.; L'Eplattenier, H. F.; Rem, A. I.; van der Lugt, J. J.; Kirpensteijn, J.

    2009-01-01

    An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact

  16. Canine obesity: an overview.

    Science.gov (United States)

    Gossellin, J; Wren, J A; Sunderland, S J

    2007-08-01

    Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20-40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.

  17. Peracute Infectious Canine Hepatitis

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    A. H. Cheema*, I. Ahmed, G. Mustafa and A. Aslam

    2012-05-01

    Full Text Available Peracute infectious canine hepatitis (ICH was diagnosed in two young male dogs out of 56 dead canines presented for necropsy examination during the period of April 2009 to June 2010. These dogs were purebred, one- month old Alsatian and 5-month old Labrador. None of the dogs had received any vaccination or deworming treatment; both had died after illness lasting for six hours and twenty four hours respectively. The dogs had shown signs of depression, anorexia and fever. At necropsy, lymph nodes were swollen, edematous and congested; livers were enlarged, bright red and mottled with numerous small white foci. Petechial hemorrhages were seen in the mucosa. Excessive serosanguinous fluid was present in the abdominal cavities. Histologically, the most significant lesion was necrohemorrhagic hepatitis with single cell necrosis of hepatocytes, lacunose dilation of sinusoids filled with blood and numerous large, solid intranuclear inclusion bodies (IIBs in the hepatocytes and macrophages. Both eosinophilic and basophilic (amphophilic inclusions were seen. It has been observed that ICH is re-emerging in some endemic countries. Pet dogs should be regularly protected by effective vaccination.

  18. Radioresistant canine hematopoietic cells

    International Nuclear Information System (INIS)

    Kawakami, T.G.; Shimizu, J.; Rosenblatt, L.S.; Goldman, M.

    1987-01-01

    Survival of dogs that are continuously exposed to a moderate dose-rate of gamma radiation (10 cGy/day) is dependent on the age of the dog at the time of exposure. Most dogs exposed postpartum to gamma radiation suffered from suppressed hematopoiesis and died of aplasia. On the other hand, none of the in utero-exposed dogs suffered from suppressed hematopoiesis and most became long-term survivors, tolerating 10-fold greater total dose, but dying of myeloproliferative disease (MPD). Using acute gamma irradiation of hematopoietic cells and colony forming unit cell assay (CFU), they observed that a canine hematopoietic cell line established from a myeloid leukemic dog that was a long-term survivor of continuous irradiation was approximately 4-fold more radioresistant than a hematopoietic cell line established from a dog with nonradiation-induced myeloid leukemia or hematopoietic cells from normal canine bone marrow. In utero dogs that are long-term survivors of continuous irradiation have radioresistant hematopoietic cells, and radioresistance that is a constitutive property of the cells

  19. Political Reputations and Campaign Promises

    OpenAIRE

    Aragones, Enriqueta; Palfrey, Thomas R.; Postlewaite, Andrew

    2006-01-01

    We analyze conditions under which candidates' reputations may affect voters' beliefs over what policy will be implemented by the winning candidate of an election. We develop a model of repeated elections with complete information in which candidates are purely ideological. We analyze an equilibrium in which voters' strategies involve a credible threat to punish candidates who renege on their campaign promises and in which all campaign promises are believed by voters and honored by candidates....

  20. Experimental study of a closed-chest pulmonary embolism-reperfusion injury canine model by means of Swan-Ganz catheter

    International Nuclear Information System (INIS)

    Bao Na; Zhai Renyou Jiang Tao; Wang Yajie; Zheng Juan; Wang Chen

    2007-01-01

    Objective: To establish a closed-chest pulmonary embolism-reperfusion animal model by Swan-Ganz catheter and to explore the mechanisms of pulmonary embolism (PE)-reperfusion injury (RI). Methods: Experiments were made on 14 mongrel dogs, ranging in weight from 15 to 18 kg, anesthetized with 3% pentobarbital sodium. The dogs were intubated with I. D. 7 endotracheal tubes. Under sterile conditions, a 7 F Swan-Ganz catheter via the external jugular vein was positioned in the unilateral pulmonary diaphragmatic lobe (DL) artery. Occlusion/reperfusion of the DL artery was controlled with 1.2 ml diluted contrast agent filled into/drawn from the balloon. After the 24 h PE, the balloon was deflated to result in 4 h reperfusion of the DL. Measurements of blood gases and tumor necrosis factor-α (TNF-α)were made at normal condition, at 24 h PE and at 4 h reperfusion. Thin-section CT scans were performed at normal condition, 24 h PE, 30 rain, 1, 2, 3 and 4 h reperfusion, respectively. At the end of each experiment, tissue specimens of bilateral diaphragmatic lobes were obtained for both wet/dry (W/D) weight ratio and for pathological study. Results: Reperfusion pulmonary edema (RPE) was an acute, mixed, noncardiogenic edema that was observed in all 14 dogs who had been successfully established as PE/RI animal models. RPE demonstrated heterogeneous ground-glass opacifications that predominated in the areas distal to the recanalized vessels. It manifested pathologically as an edematous lung infihrated by inflammatory cells. The mean of PaO 2 and TNF-α of 4 h reperfusion was (81 ± 4) mm Hg( 1 mm Hg =0.133 kPa) and (16.0 ± 2.5)pg/ml, which were significantly different (P<0.05) from normal value [(96 ± 6)mm Hg and (13.9 ± 2.0) pg/ml]. The W/D of the injured lung (6.3 ± 1.2) was significantly greater (P<0.01) than that of the contralateral lung (4.5 ± 1.2), suggesting that the increase in the lung water was due to reperfusion injury. Conclusion: The closed-chest canine model

  1. A retrospective investigation on canine papillomavirus 1 (CPV1 in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer.

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    Ilaria Porcellato

    Full Text Available CPV1 (also called COPV is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs, but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas and 10 hyperplastic lesions (gingival hyperplasia were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10% SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

  2. A retrospective investigation on canine papillomavirus 1 (CPV1) in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer.

    Science.gov (United States)

    Porcellato, Ilaria; Brachelente, Chiara; Guelfi, Gabriella; Reginato, Alice; Sforna, Monica; Bongiovanni, Laura; Mechelli, Luca

    2014-01-01

    CPV1 (also called COPV) is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs), but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE) canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas) and 10 hyperplastic lesions (gingival hyperplasia) were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10%) SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

  3. A compendium of canine normal tissue gene expression.

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    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  4. Using euhalophytes to understand salt tolerance and to develop saline agriculture: Suaeda salsa as a promising model.

    Science.gov (United States)

    Song, Jie; Wang, Baoshan

    2015-02-01

    As important components in saline agriculture, halophytes can help to provide food for a growing world population. In addition to being potential crops in their own right, halophytes are also potential sources of salt-resistance genes that might help plant breeders and molecular biologists increase the salt tolerance of conventional crop plants. One especially promising halophyte is Suaeda salsa, a euhalophytic herb that occurs both on inland saline soils and in the intertidal zone. The species produces dimorphic seeds: black seeds are sensitive to salinity and remain dormant in light under high salt concentrations, while brown seeds can germinate under high salinity (e.g. 600 mm NaCl) regardless of light. Consequently, the species is useful for studying the mechanisms by which dimorphic seeds are adapted to saline environments. S. salsa has succulent leaves and is highly salt tolerant (e.g. its optimal NaCl concentration for growth is 200 mm). A series of S. salsa genes related to salt tolerance have been cloned and their functions tested: these include SsNHX1, SsHKT1, SsAPX, SsCAT1, SsP5CS and SsBADH. The species is economically important because its fresh branches have high value as a vegetable, and its seed oil is edible and rich in unsaturated fatty acids. Because it can remove salts and heavy metals from saline soils, S. salsa can also be used in the restoration of salinized or contaminated saline land. Because of its economic and ecological value in saline agriculture, S. salsa is one of the most important halophytes in China. In this review, the value of S. salsa as a source of food, medicine and forage is discussed. Its uses in the restoration of salinized or contaminated land and as a source of salt-resistance genes are also considered. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Extraglandular and intraglandular vascularization of canine prostate.

    Science.gov (United States)

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

  6. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

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    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  7. Increasing Incidence of Canine Leptospirosis in Switzerland

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    Andrea Major

    2014-07-01

    Full Text Available A marked increase in canine leptospirosis was observed in Switzerland over 10 years with a peak incidence of 28.1 diagnosed cases/100,000 dogs/year in the most affected canton. With 95% affected dogs living at altitudes <800 m, the disease presented a seasonal pattern associated with temperature (r2 0.73 and rainfall (r2 0.39, >90% cases being diagnosed between May and October. The increasing yearly incidence however was only weakly correlated with climatic data including number of summer (r2 0.25 or rainy days (r2 0.38. Serovars Australis and Bratislava showed the highest seropositivity rates with 70.5% and 69.1%, respectively. Main clinical manifestations included renal (99.6%, pulmonary (76.7%, hepatic (26.0%, and hemorrhagic syndromes (18.2%, leading to a high mortality rate (43.3%. Similar to the human disease, liver involvement had the strongest association with negative outcome (OR 16.3. Based on these data, canine leptospirosis presents similar features and severity as the human infection for which it therefore can be considered a model. Its re-emergence in a temperate country with very high incidence rates in canines should thus be viewed as a warning and emphasize the need for increased awareness in other species.

  8. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

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    Hille Fieten

    2016-01-01

    Full Text Available The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional

  9. Anisotropic Conductivity Tensor Imaging of In Vivo Canine Brain Using DT-MREIT.

    Science.gov (United States)

    Jeong, Woo Chul; Sajib, Saurav Z K; Katoch, Nitish; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2017-01-01

    We present in vivo images of anisotropic electrical conductivity tensor distributions inside canine brains using diffusion tensor magnetic resonance electrical impedance tomography (DT-MREIT). The conductivity tensor is represented as a product of an ion mobility tensor and a scale factor of ion concentrations. Incorporating directional mobility information from water diffusion tensors, we developed a stable process to reconstruct anisotropic conductivity tensor images from measured magnetic flux density data using an MRI scanner. Devising a new image reconstruction algorithm, we reconstructed anisotropic conductivity tensor images of two canine brains with a pixel size of 1.25 mm. Though the reconstructed conductivity values matched well in general with those measured by using invasive probing methods, there were some discrepancies as well. The degree of white matter anisotropy was 2 to 4.5, which is smaller than previous findings of 5 to 10. The reconstructed conductivity value of the cerebrospinal fluid was about 1.3 S/m, which is smaller than previous measurements of about 1.8 S/m. Future studies of in vivo imaging experiments with disease models should follow this initial trial to validate clinical significance of DT-MREIT as a new diagnostic imaging modality. Applications in modeling and simulation studies of bioelectromagnetic phenomena including source imaging and electrical stimulation are also promising.

  10. Root Length and Anatomy of Impacted Maxillary Canines in Patients with Unilateral Maxillary Canine Impaction

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    Mostfa Shahabi

    2017-09-01

    Full Text Available Introduction: Canine impaction is a common occurrence. In this study, we sought to investigate the root anatomy and length of impacted canines and lateral incisor adjacent to impacted maxillary canine. Materials and Methods: In this retrospective study, three-dimensional tomographic imaging was performed on 26 patients with unilateral maxillary canine impaction. In this study, we evaluated root length and anatomy of impacted canines, in terms of resorption intensity and curvature, with Planmeca Romexis Viewer 4.0. Furthermore, crown shape as well as root length and anatomy of the lateral incisors adjacent to impacted canines were investigated and compared with the other side on the dental arch, where canine eruption was normal. Results: Root length of impacted canines was significantly lower than that of normal canines (P=0.011. There were no significant differences between root length of lateral incisors adjacent to impacted canines and root length of lateral incisors adjacent to normal canines (P=0.221. Moreover, the resorption intensity of the adjacent lateral incisors was higher than that of the impacted canines. No significant differences were noted in root resorption intensity between the lateral incisors adjacent to the imacted canines and the lateral incisors adjacent to normal canines (P=0.36. In addition, resorption intensity was significantly higher in impacted canines than in normal canines (P=0.024. Root anatomy of impacted canines was not significantly different from that of normal canines (P=0.055. The crown shape of the lateral incisors adjacent to impacted canines was not significantly different from that of the lateral incisors adjacent to normal canines (P=0.052. Conclusion: Impaction can probably affect root length and canine resorption severity. However, root and crown shape of lateral incisors cannot always be associated with canine impaction.

  11. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.

    Science.gov (United States)

    Gharagozloo, P; Gutiérrez-Adán, A; Champroux, A; Noblanc, A; Kocer, A; Calle, A; Pérez-Cerezales, S; Pericuesta, E; Polhemus, A; Moazamian, A; Drevet, J R; Aitken, R J

    2016-02-01

    Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress? Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress. Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive. The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates. In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded. Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the

  12. Dynamic In Vivo Profiling of DNA Damage and Repair after Radiotherapy Using Canine Patients as a Model

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    Nadine Schulz

    2017-06-01

    Full Text Available Time resolved data of DNA damage and repair after radiotherapy elucidates the relation between damage, repair, and cell survival. While well characterized in vitro, little is known about the time-course of DNA damage response in tumors sampled from individual patients. Kinetics of DNA damage after radiotherapy was assessed in eight dogs using repeated in vivo samples of tumor and co-irradiated normal tissue analyzed with comet assay and phosphorylated H2AX (γH2AX immunohistochemistry. In vivo results were then compared (in silico with a dynamic mathematical model for DNA damage formation and repair. Maximum %DNA in tail was observed at 15–60 min after irradiation, with a rapid decrease. Time-courses of γH2AX-foci paralleled these findings with a small time delay and were not influenced by covariates. The evolutionary parameter search based on %DNA in tail revealed a good fit of the DNA repair model to in vivo data for pooled sarcoma time-courses, but fits for individual sarcoma time-courses suffer from the heterogeneous nature of the in vivo data. It was possible to follow dynamics of comet tail intensity and γH2AX-foci during a course of radiation using a minimally invasive approach. DNA repair can be quantitatively investigated as time-courses of individual patients by integrating this resulting data into a dynamic mathematical model.

  13. IQGAP1 is an oncogenic target in canine melanoma.

    Directory of Open Access Journals (Sweden)

    Becky H Lee

    Full Text Available Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60% or Nras (20%, human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

  14. Citizen science: a new direction in canine behavior research.

    Science.gov (United States)

    Hecht, Julie; Spicer Rice, Eleanor

    2015-01-01

    Researchers increasingly rely on members of the public to contribute to scientific projects-from collecting or identifying, to analyzing and disseminating data. The "citizen science" model proves useful to many thematically distinctive fields, like ornithology, astronomy, and phenology. The recent formalization of citizen science projects addresses technical issues related to volunteer participation--like data quality--so that citizen scientists can make longstanding, meaningful contributions to scientific projects. Since the late 1990s, canine science research has relied with greater frequency on the participation of the general public, particularly dog owners. These researchers do not typically consider the methods and technical issues that those conducting citizen science projects embrace and continue to investigate. As more canine science studies rely on public input, an in-depth knowledge of the benefits and challenges of citizen science can help produce relevant, high-quality data while increasing the general public's understanding of canine behavior and cognition as well as the scientific process. We examine the benefits and challenges of current citizen science models in an effort to enhance canine citizen science project preparation, execution, and dissemination. This article is part of a Special Issue entitled: Canine Behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  16. Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

    Directory of Open Access Journals (Sweden)

    Manuela Gaebler

    2017-09-01

    Full Text Available Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

  17. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    OpenAIRE

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-01-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice ...

  18. Evaluating coronary reperfusion during acute myocardial infarction in a canine model by gadolinium-DTPA-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Kazuaki; Ishibashi, Yutaka; Shimada, Toshio (Shimane Medical Univ., Izumo (Japan)) (and others)

    1993-05-01

    In previous studies, magnetic resonance imaging (MRI) using contrast agents was found to be useful in distinguishing reperfused infarcts from nonreperfused infarcts. However, there have been only a few detailed studies using consecutive MR images for the assessment of myocardial reperfusion during an acute infarction and also no studies have been performed using a percutaneous transluminal coronary occlusion model (closed chest model). We induced acute myocardial infarction in dogs by occluding and then reperfusing the coronary artery with a balloon catheter. ECG-gated MR images were taken using the spin-echo technique before and after Gd-DTPA injection during both coronary artery occlusion and after reperfusion. We defined the intensity ratio (IR) as the signal intensity at the ischemic area divided by that at the nonischemic area on MR images and compared each image by the IR. Without Gd-DTPA, there was no difference between infarcted and normally perfused myocardium. Infarcted myocardium had a low signal intensity (IR=0.68[+-]0.14) soon after Gd-DTPA injection. This difference diminished with time. After reperfusion the infarcted myocardium had a high signal intensity (IR: 1.76[+-]0.34). We conclude that Gd-DTPA-enhanced MRI can distinguish reperfused from nonreperfused infarcts soon after Gd-DTPA administration. (author).

  19. Evaluating coronary reperfusion during acute myocardial infarction in a canine model by gadolinium-DTPA-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Tanabe, Kazuaki; Ishibashi, Yutaka; Shimada, Toshio

    1993-01-01

    In previous studies, magnetic resonance imaging (MRI) using contrast agents was found to be useful in distinguishing reperfused infarcts from nonreperfused infarcts. However, there have been only a few detailed studies using consecutive MR images for the assessment of myocardial reperfusion during an acute infarction and also no studies have been performed using a percutaneous transluminal coronary occlusion model (closed chest model). We induced acute myocardial infarction in dogs by occluding and then reperfusing the coronary artery with a balloon catheter. ECG-gated MR images were taken using the spin-echo technique before and after Gd-DTPA injection during both coronary artery occlusion and after reperfusion. We defined the intensity ratio (IR) as the signal intensity at the ischemic area divided by that at the nonischemic area on MR images and compared each image by the IR. Without Gd-DTPA, there was no difference between infarcted and normally perfused myocardium. Infarcted myocardium had a low signal intensity (IR=0.68±0.14) soon after Gd-DTPA injection. This difference diminished with time. After reperfusion the infarcted myocardium had a high signal intensity (IR: 1.76±0.34). We conclude that Gd-DTPA-enhanced MRI can distinguish reperfused from nonreperfused infarcts soon after Gd-DTPA administration. (author)

  20. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Shinya; Hanazono, Kiwamu [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi [Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Iwano, Hidetomo [Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Uchide, Tsuyoshi, E-mail: uchide@rakuno.ac.jp [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan)

    2013-09-13

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM

  1. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Dammy Pinheiro

    Full Text Available The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL, proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01 and overall survival (hazard ratio 1.61; p = 0.01 when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  2. Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2016-02-01

    Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P dilated cardiomyopathy heart.

  3. Tricuspid leaflet resection in an open beating heart for the creation of a canine tricuspid regurgitation model.

    Science.gov (United States)

    Xie, Xu-jing; Liao, Sheng-jie; Wu, Yue-heng; Lu, Cong; Zhu, Ping; Fei, Hong-wen; Xiao, Xue-jun; Huang, Huan-lei

    2016-02-01

    Outcomes of tricuspid valve replacement are poor, partly due to right heart remodelling. The research on its underlying mechanisms is hampered by a lack of animal models of tricuspid regurgitation (TR). Our objective was to create a reproducible and clinically compatible TR animal model to study right heart remodelling caused by TR. Fourteen juvenile male Beagle dogs were divided randomly into an intervention group (n = 11) and a sham-operated control group (n = 3). The intervention group underwent thoracotomy and right atrial incision following superior and inferior vena caval occlusion. The anterior leaflet, together with the chordae, of the tricuspid valve was resected in eight dogs ('one leaflet' group), whereas both anterior and posterior leaflets, together with the chordae, were resected in three dogs ('two leaflets' group). The right atrium and chest were then closed. The control group underwent the same procedure, except leaflet resection. One dog from the 'two leaflets' group and one control dog were sacrificed and autopsy was performed at 12 months post-surgery. All dogs survived over the 1-year observation period postoperatively. TR grade IV occurred immediately postoperatively in the 'one leaflet' group, and TR grade IV plus in the 'two leaflets' group. The overall procedure lasted 30-40 min, and the mean time of vena caval occlusion was 87 ± 10 s. Central venous pressure increased from 6 ± 1.2 at baseline to 13 ± 1.7 mmHg (P heart remodelling. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  4. Keeping the Promise

    Science.gov (United States)

    Whissemore, Tabitha

    2016-01-01

    Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…

  5. Methods of modeling TCO residential real estate in the life cycles of buildings as a promising energy efficiency management tool

    Directory of Open Access Journals (Sweden)

    Kulakov Kirill

    2017-01-01

    Full Text Available Building and developing an affordable housing market is a huge challenge for Russia’s national economy. Today, the housing construction industry finds itself in a situation torn by a conflict caused by the simultaneous needs to minimize the housing construction costs in order to make housing more affordable for Russians and to increase the energy efficiency of the housing projects, which is associated with additional costs for developers. To find solutions to this contradictory situation, one needs new theoretical and practical approaches and economic tools. The global economic trend of managing goods and services on the basis of the value of goods and services over the life cycle is also manifested in the construction industry in Russia. The problem of forming a new economic thinking in the housing sector predetermines the perception of the value of housing not only as the price of purchased real estate, but as the equivalent of the total cost of ownership of real estate throughout its life cycle. This approach allows to compensate the initial rise in the cost of construction resulting from the introduction of energy-efficient technologies by savings in the operational phase of the life cycle of the property. In this regard, management of the total cost of real estate ownership based on energy modeling is of high research and practical relevance.

  6. Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

    NARCIS (Netherlands)

    Renkema, Anne-Marie; Renkema, Alianne; Bronkhorst, Ewald; Katsaros, Christos

    Introduction: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the

  7. Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

    NARCIS (Netherlands)

    Renkema, A.M.; Bronkhorst, E.M.; Katsaros, C.

    2011-01-01

    INTRODUCTION: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the

  8. Effect of methylprednisolone upon technetium-99m pyrophosphate assessment of myocardial necrosis in the canine countershock model

    International Nuclear Information System (INIS)

    Schneider, R.M.; Hayslett, J.P.; Downing, S.E.; Berger, H.J.; Donabedian, R.K.; Zaret, B.L.

    1977-01-01

    RRepeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-/sup 99m/ pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P < 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in MP dogs, resulting in accelerated urinary excretion of PYP (46.9 +- 3.6 vs 35.8 +- 2.4 percent injected dose in one hour, P < 0.01), and reduced blood PYP. Thus, MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data

  9. Bone regeneration by gelatin hydro-gel seat containing BMP-2 and its application to canine orbital floor fracture Model

    International Nuclear Information System (INIS)

    Mochizuki, Yuichi

    2007-01-01

    Reported are preparation of the gel seat in the title (GHG) for sustained release of BMP-2 (bone morphogenetic protein-2) and its application to the fracture model of orbital floor of the dog. The chemically linked GHG was prepared from gelatin and glutaraldehyde and lyophilized. BMP-2 solution was dropped on the GHG seat to be contained there. To see the biobehavior of BMP-2 and GHG, they were labeled with 125 I and were given subcutaneously in the back of nude mice, of which remaining radioactivity was periodically measured by Aloka ARC-310B gamma counter. This experiment revealed the sustained release of BMP-2 along with degradation of the GHG. Then a complex of the GHG and bio-degradable polymer (L-lactide-ε-caprolactone) was prepared and implanted to the artificially fractured region (10 x 10 mm) of dog orbit floor, of which recovering process was evaluated by analysis of bone structure with soft X-ray (SOFRON, TRS-1005) roentgenography, histology, and micro-CT imaging (Comscantecno's Scan Xmate-A090S) for trabecular bone volume, thickness, number and separation. This experiment revealed that new bone was effectively induced to regenerate on the complex, of which structure was found similar to the normal trabecula. Thus in future, the complex can be useful for ideal treatment of the orbit floor fracture without necessity of donor. (R.T.)

  10. Using canine osteosarcoma as a model to assess efficacy of novel therapies: can old dogs teach us new tricks?

    Science.gov (United States)

    Rodriguez, Carlos O

    2014-01-01

    Since its domestication more than 10,000 years ago, the dog has been the animal that most intimately shares our work and homelife. Interestingly, the dog also shares many of our diseases including cancer such as osteosarcoma. Like the human, osteosarcoma is the most common bone malignancy of the dog and death from pulmonary metastasis is the most common outcome. The incidence of this spontaneous bone neoplasm occurs ten times more frequently that it does so in children with about 8,000-10,000 cases estimated to occur in dogs in the USA. Because there is no "standard of care" in veterinary medicine, the dog can also serve us by being a model for this disease in children. Although the most common therapy for the dog with osteosarcoma is amputation followed by chemotherapy, not all owners choose this route. Consequently, novel therapeutic interventions can be attempted in the dog with or without chemotherapy that could not be done in humans with osteosarcoma due to ethical concerns. This chapter will focus on the novel therapies in the dog that have been reported or are in veterinary clinical trials at the author's institution. It is hoped that collaboration between veterinary oncologists and pediatric oncologists will lead to the development of novel therapies for (micro- or macro-) metastatic osteosarcoma that improve survival and might ultimately lead to a cure in both species.

  11. Heat dissipation by blood circulation and airway tissue heat absorption in a canine model of inhalational thermal injury.

    Science.gov (United States)

    Wan, Jiangbo; Zhang, Guoan; Qiu, Yuxuan; Wen, Chunquan; Fu, Tairan

    2016-05-01

    This study aimed to further explore heat dissipation by blood circulation and airway tissue heat absorption in an inhalational thermal injury model. Twelve adult male Beagle dogs were divided into four groups to inhale heated air for 10min: the control group, group I (100.5°C), group II (161.5°C), and group III (218°C). The relative humidity and temperature of the inhaled heated air were measured in the heating tube and trachea, as were blood temperatures and flow velocities in both common jugular veins. Formulas were used to calculate the total heat quantity reduction of the heated air, heat dissipation by the blood, and airway tissue heat absorption. The blood temperatures of both the common jugular veins increased by 0.29°C±0.07°C to 2.96°C±0.24°C and the mean blood flow volume after injury induction was about 1.30-1.74 times greater than before injury induction. The proportions of heat dissipated by the blood and airway tissue heat absorption were 68.92%±14.88% and 31.13%±14.87%, respectively. The heat dissipating ability of the blood circulation was demonstrated and improved upon along with tissue heat absorption owing to increased regional blood flow. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  12. Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

    2016-08-22

    Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

  13. Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

    Science.gov (United States)

    Smith, Jennifer A; Anderson, Sarah-Jane; Harris, Kate L; McGillen, Jessica B; Lee, Edward; Garnett, Geoff P; Hallett, Timothy B

    2016-07-01

    Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful

  14. Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

    Science.gov (United States)

    Lee, Young Mok; Conlon, Thomas J; Specht, Andrew; Coleman, Kirsten E; Brown, Laurie M; Estrella, Ana M; Dambska, Monika; Dahlberg, Kathryn R; Weinstein, David A

    2018-05-25

    Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

  15. Transoral endoscopic surgery versus conventional thoracoscopic surgery for thoracic intervention: safety and efficacy in a canine survival model.

    Science.gov (United States)

    Liu, Chien-Ying; Chu, Yen; Wu, Yi-Cheng; Yuan, Hsu-Chia; Ko, Po-Jen; Liu, Yun-Hen; Liu, Hui-Ping

    2013-07-01

    Transoral endoscopic surgery has been shown to be feasible and safe in both humans and animal models. The purpose of this study was to evaluate the safety and efficacy of transoral and conventional thoracoscopy for thoracic exploration, surgical lung biopsy, and pericardial window creation. The animals (n = 20) were randomly assigned to the transoral endoscopic approach group (n = 10) or conventional thoracoscopic approach group (n = 10). Transoral thoracoscopy was performed with a flexible bronchoscope via an incision over the vestibulum oris. In conventional thoracoscopy, access to the thoracic cavity was obtained through a thoracic incision. Surgical outcomes (body weight, operating time, operative complications, and time to resumption of normal diet), physiologic parameters (respiratory rate, body temperature), inflammatory parameters [white blood cell (WBC) counts and C-reactive protein (CRP)], and pulmonary parameters (arterial blood gases) were compared for both procedures. The surgical lung biopsy and pericardial window creation were successfully performed in all animals except one animal in the transoral group. There was no significant difference in operating times between the groups. The increase in WBC in the transoral thoracoscopy group was significantly smaller on postoperative day 1 than in the conventional thoracoscopy group (p = 0.0029). The transoral group had an earlier return to preoperative body temperature (p = 0.041) and respiratory rate (p = 0.045) on day 7. With respect to pulmonary parameters, there was no significant difference in blood pH, pCO2, or PaCO2 between the transoral and transthoracic groups. All animals survived without complications 14 days after surgery. This study demonstrated that the transoral approach was comparable to conventional thoracoscopic surgery for lung biopsy and pericardial window creation in terms of safety and efficacy.

  16. Root Length and Anatomy of Impacted Maxillary Canines in Patients with Unilateral Maxillary Canine Impaction

    OpenAIRE

    Mostfa Shahabi; Maryam Omidkhoda; Seyedeh Haniyeh Omidi; Seyed Hosein Hoseini Zarch

    2017-01-01

    Introduction: Canine impaction is a common occurrence. In this study, we sought to investigate the root anatomy and length of impacted canines and lateral incisor adjacent to impacted maxillary canine. Materials and Methods: In this retrospective study, three-dimensional tomographic imaging was performed on 26 patients with unilateral maxillary canine impaction. In this study, we evaluated root length and anatomy of impacted canines, in terms of resorption intensity and curvature, with Planme...

  17. The effects of sulforaphane on canine osteosarcoma proliferation and invasion.

    Science.gov (United States)

    Rizzo, V L; Levine, C B; Wakshlag, J J

    2017-09-01

    Recent evidence in in vitro and in vivo models suggests that sulforaphane (SFN), found in raw cruciferous vegetables, may have utility in chemoprevention, as an antineoplastic agent and as a free radical scavenger. The effects of SFN alone or with doxorubicin on cell viability were examined, as well as cell cycle kinetics, invasion capabilities and apoptosis in three canine osteosarcoma cell line (D17, OS 2.4 and HMPOS). Results showed that SFN could not induce cell death at potentially physiological concentrations (canine osteosarcoma. © 2016 John Wiley & Sons Ltd.

  18. Promise Zones for Applicants

    Data.gov (United States)

    Department of Housing and Urban Development — This tool assists applicants to HUD's Promise Zone initiative prepare data to submit with their application by allowing applicants to draw the exact location of the...

  19. Identification of quantitative trait loci (QTL for canine hip dysplasia and canine elbow dysplasia in Bernese mountain dogs.

    Directory of Open Access Journals (Sweden)

    Sophia Pfahler

    Full Text Available A genome-wide association study for canine hip dysplasia (CHD and canine elbow dysplasia (CED using the Illumina canine high density bead chip had been performed for 174 Bernese mountain dogs. General and mixed linear model analysis identified two different regions with single nucleotide polymorphisms (SNPs on dog chromosome (CFA 14 significantly associated with CHD and a further significantly CHD-associated region on CFA37. For CED, four SNPs on CFA11 and 27 were significantly associated. The identified SNPs of four associated regions included nearby candidate genes. These possible positional candidates were the genes PON2 on CFA14 and FN1 on CFA37 for CHD and the genes LMNB1 on CFA11 and WNT10B on CFA27 for CED.

  20. Maxillary canine teeth as supplement tool in sex determination ...

    African Journals Online (AJOL)

    Maxillary impressions for all subjects were taken in alginate impression material. Study models were prepared immediately in dental stone to prevent dimensional change. Apart from the inter-canine distance and the left mesio-distal crown width which exhibited statistically significant differences, other parameters as ...

  1. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  2. Approaches to canine health surveillance.

    Science.gov (United States)

    O'Neill, Dan G; Church, David B; McGreevy, Paul D; Thomson, Peter C; Brodbelt, Dave C

    2014-01-01

    Effective canine health surveillance systems can be used to monitor disease in the general population, prioritise disorders for strategic control and focus clinical research, and to evaluate the success of these measures. The key attributes for optimal data collection systems that support canine disease surveillance are representativeness of the general population, validity of disorder data and sustainability. Limitations in these areas present as selection bias, misclassification bias and discontinuation of the system respectively. Canine health data sources are reviewed to identify their strengths and weaknesses for supporting effective canine health surveillance. Insurance data benefit from large and well-defined denominator populations but are limited by selection bias relating to the clinical events claimed and animals covered. Veterinary referral clinical data offer good reliability for diagnoses but are limited by referral bias for the disorders and animals included. Primary-care practice data have the advantage of excellent representation of the general dog population and recording at the point of care by veterinary professionals but may encounter misclassification problems and technical difficulties related to management and analysis of large datasets. Questionnaire surveys offer speed and low cost but may suffer from low response rates, poor data validation, recall bias and ill-defined denominator population information. Canine health scheme data benefit from well-characterised disorder and animal data but reflect selection bias during the voluntary submissions process. Formal UK passive surveillance systems are limited by chronic under-reporting and selection bias. It is concluded that active collection systems using secondary health data provide the optimal resource for canine health surveillance.

  3. FLT3 mutations in canine acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Suter, Steven E; Small, George W; Seiser, Eric L; Thomas, Rachael; Breen, Matthew; Richards, Kristy L

    2011-01-01

    FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations. We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting. The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations. These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias

  4. Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    John Kuchtey

    2011-02-01

    Full Text Available Primary open angle glaucoma (POAG is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies.

  5. Biomechanical comparison of 3.0 mm headless compression screw and 3.5 mm cortical bone screw in a canine humeral condylar fracture model.

    Science.gov (United States)

    Gonsalves, Mishka N; Jankovits, Daniel A; Huber, Michael L; Strom, Adam M; Garcia, Tanya C; Stover, Susan M

    2016-09-20

    To compare the biomechanical properties of simulated humeral condylar fractures reduced with one of two screw fixation methods: 3.0 mm headless compression screw (HCS) or 3.5 mm cortical bone screw (CBS) placed in lag fashion. Bilateral humeri were collected from nine canine cadavers. Standardized osteotomies were stabilized with 3.0 mm HCS in one limb and 3.5 mm CBS in the contralateral limb. Condylar fragments were loaded to walk, trot, and failure loads while measuring construct properties and condylar fragment motion. The 3.5 mm CBS-stabilized constructs were 36% stiffer than 3.0 mm HCS-stabilized constructs, but differences were not apparent in quality of fracture reduction nor in yield loads, which exceeded expected physiological loads during rehabilitation. Small residual fragment displacements were not different between CBS and HCS screws. Small fragment rotation was not significantly different between screws, but was weakly correlated with moment arm length (R² = 0.25). A CBS screw placed in lag fashion provides stiffer fixation than an HCS screw, although both screws provide similar anatomical reduction and yield strength to condylar fracture fixation in adult canine humeri.

  6. Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: a systematic review.

    Science.gov (United States)

    Wingbermühle, Roel W; van Trijffel, Emiel; Nelissen, Paul M; Koes, Bart; Verhagen, Arianne P

    2018-01-01

    Which multivariable prognostic model(s) for recovery in people with neck pain can be used in primary care? Systematic review of studies evaluating multivariable prognostic models. People with non-specific neck pain presenting at primary care. Baseline characteristics of the participants. Recovery measured as pain reduction, reduced disability, or perceived recovery at short-term and long-term follow-up. Fifty-three publications were included, of which 46 were derivation studies, four were validation studies, and three concerned combined studies. The derivation studies presented 99 multivariate models, all of which were at high risk of bias. Three externally validated models generated usable models in low risk of bias studies. One predicted recovery in non-specific neck pain, while two concerned participants with whiplash-associated disorders (WAD). Discriminative ability of the non-specific neck pain model was area under the curve (AUC) 0.65 (95% CI 0.59 to 0.71). For the first WAD model, discriminative ability was AUC 0.85 (95% CI 0.79 to 0.91). For the second WAD model, specificity was 99% (95% CI 93 to 100) and sensitivity was 44% (95% CI 23 to 65) for prediction of non-recovery, and 86% (95% CI 73 to 94) and 55% (95% CI 41 to 69) for prediction of recovery, respectively. Initial Neck Disability Index scores and age were identified as consistent prognostic factors in these three models. Three externally validated models were found to be usable and to have low risk of bias, of which two showed acceptable discriminative properties for predicting recovery in people with neck pain. These three models need further validation and evaluation of their clinical impact before their broad clinical use can be advocated. PROSPERO CRD42016042204. [Wingbermühle RW, van Trijffel E, Nelissen PM, Koes B, Verhagen AP (2018) Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: a systematic review

  7. Promising More Information

    Science.gov (United States)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  8. NCR1 Expression Identifies Canine Natural Killer Cell Subsets with Phenotypic Similarity to Human Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Ann Foltz

    2016-11-01

    Full Text Available Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46, the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization. We demonstrate that CD3-/NKp46+ cells in healthy and osteosarcoma-bearing canines have phenotypic similarity to human CD3-/NKp46+ NK cells, expressing mRNA for CD16 and the natural cytotoxicity receptors NKp30, NKp44, and NKp80. Functionally, we demonstrate with the calcein release assay that canine CD3-/NKp46+ cells kill canine tumor cell lines without prior sensitization and secrete IFN-γ, TNF-α, IL-8, IL-10, and GM-CSF as measured by Luminex. Like human NK cells, CD3-/NKp46+ cells expand rapidly on feeder cells expressing 4-1BBL and membrane-bound IL-21 (median= 20,283-fold in 21 days. Further, we identify a minor Null population (CD3-/CD21-/CD14-/NKp46- with reduced cytotoxicity against osteosarcoma cells, but similar cytokine secretion as CD3-/NKp46+ cells. Null cells in canines and humans have reduced expression of NKG2D, NKp44, and CD16 compared to NKp46+ NK cells, and can be induced to express NKp46 with further expansion on feeder cells. In conclusion, we have identified and characterized canine NK cells, including an NKp46- subset of canine and human NK cells, using a novel anti-canine NKp46 antibody, and report robust ex vivo expansion of canine NK cells sufficient for adoptive immunotherapy.

  9. Reference genes for reverse transcription quantitative PCR in canine brain tissue

    NARCIS (Netherlands)

    Stassen, Quirine E M; Riemers, Frank M; Reijmerink, Hannah; Leegwater, Peter A J; Penning, Louis C

    2015-01-01

    BACKGROUND: In the last decade canine models have been used extensively to study genetic causes of neurological disorders such as epilepsy and Alzheimer's disease and unravel their pathophysiological pathways. Reverse transcription quantitative polymerase chain reaction is a sensitive and

  10. Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection

    Science.gov (United States)

    Hosein, Shazia; Rodríguez-Cortés, Alhelí; Blake, Damer P.; Allenspach, Karin; Alberola, Jordi; Solano-Gallego, Laia

    2015-01-01

    Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in

  11. Canine and feline colostrum.

    Science.gov (United States)

    Chastant-Maillard, S; Aggouni, C; Albaret, A; Fournier, A; Mila, H

    2017-04-01

    Puppy and kitten survival over the first weeks is particularly dependent on colostrum, a specific secretion of the mammary gland produced during the first 2 days post-partum. Colostrum is a source of nutrients and immunoglobulins. It also contributes to the digestive tract maturation. Colostrum differentiates from milk mainly based on its concentration in immunoglobulins G: 20-30 g/L in dog colostrum, 40-50 g/L in cats' vs <1 g/L in milk. IgG concentration rapidly drops after parturition (-50% in 24 hr). Immune quality of colostrum is highly variable between bitches, with no relationship with maternal blood IgG level, dam's age, breed size or litter size. In addition to systemic immune protection, colostrum also plays a major role for local digestive protection, due to IgA, lysozyme, lactoferrin, white blood cells and various cytokines. Energetic concentration of canine and feline colostrum is not superior to that of mature milk. It depends on colostrum fat concentration and is affected by breed size (higher in breeds <10 kg adult body weight). As puppies and kittens are almost agammaglobulinemic at birth, transfer of IgG from their digestive tract into their bloodstream is crucial for their survival, IgG absorption ending at 12-16 hr after birth. Energetic supply over the two first days of life, as evidenced by growth rate over the two first days of life, also affects risk of neonatal mortality. Early and sufficient suckling of colostrum is thus the very first care to be provided to newborns for their later health and survival. © 2016 Blackwell Verlag GmbH.

  12. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Directory of Open Access Journals (Sweden)

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  13. Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia. A PET study in rat and canine models of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Hashimoto, Tadatoshi

    2000-01-01

    Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the tricarboxylic acid (TCA) cycle after β-oxidation. We speculate that [1- 11 C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1- 11 C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [ 15 O]H 2 O measured 1-2 h and 5-6 h after insult was compared with that of [1- 11 C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [ 15 O]H 2 O were lower than those determined with [1- 11 C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1- 11 C]octanoate was observed in the ischemic regions. The uptake of [1- 11 C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1- 11 C]octanoate provides functional information different from CBF. In conclusion, we found that [1- 11 C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. (author)

  14. Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.

    Science.gov (United States)

    Zhu, Yujie; Hanafy, Mohamed A; Killingsworth, Cheryl R; Walcott, Gregory P; Young, Martin E; Pogwizd, Steven M

    2014-01-01

    Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.

  15. Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.

    Directory of Open Access Journals (Sweden)

    Yujie Zhu

    Full Text Available Patients with chronic heart failure (CHF exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT, traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2, correlation dimension (CD, and Shannon entropy (SE at baseline, as well as 240 days (240 d and 720 days (720 d following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d. Morning rise in the ratio of low frequency to high frequency (LF/HF HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.

  16. A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2013-08-01

    Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  17. Evaluating Quantitative and Qualitative Traits of Promising Potato Clones and Commercial Cultivars Using the GGE Bi-plot and AMMI Models

    Directory of Open Access Journals (Sweden)

    D HassanPanah

    2014-07-01

    Full Text Available To evaluate quantitative and qualitative characteristics and stability of marketable tuber yield of 13 promising potato clones, along with three commercial cultivars (Agria, Marfona and Lady Rosetta as checks, an experiment was based on a randomized complete block design with four replications was carried out at the Agricultural and Natural Resources Research Station of Ardabil during 2011 and 2012. During the growing period and after harvest, attributes like number of main stem per plant, plant height, tuber number and weight per plant, total and marketable tuber yield, dry matter percentage, baking type, hollow heart, tuber inner ring and discoloration of raw tuber flesh after 24 hours were measured. Combined ANONA for quantitative traits showed that there were significant differences among promising clones as to total and marketable tuber yield, tuber number and weight per plant, plant height, mean tuber weight, number of main stem per plant and dry matter percentage and their interactions with year in total and marketable tuber yield and tuber number and weight per plant. The clones 396151-7, 397008-5, 397015-8, 397008-2 and 994001-4 were found to have higher total and marketable tuber yield, tuber number and weight per plant and mean tuber weight. These clones produced high and mid-uniform tuber, yellow skin color, yellow and white flesh color, oval round and round tuber shape, mid and shallow eyes, with no hollow heart, tuber inner crack and tuber inner ring, mid-late maturity and mid and high dry matter percentage as compared with control and other clones. In this experiment, GGE Bi-plot and AMMI models were found to be proper methods for selection of 397008-2, 397008-5 and 994001-4 as being high marketable and stable yielding clones.

  18. Cytogenetic analysis of CpG-oligonucleotide DSP30 plus Interleukin-2-Stimulated canine B-Cell lymphoma cells reveals the loss of one X Chromosome as the sole abnormality.

    Science.gov (United States)

    Reimann-Berg, N; Murua Escobar, H; Kiefer, Y; Mischke, R; Willenbrock, S; Eberle, N; Nolte, I; Bullerdiek, J

    2011-01-01

    Human and canine lymphoid neoplasms are characterized by non-random cytogenetic abnormalities. However, due to the low mitotic activity of the B cells, cytogenetic analyses of B-cell lymphoid proliferations are difficult to perform. In the present study we stimulated canine B-cell lymphoma cells with the immunostimulatory CpG-oligonucleotide DSP30 in combination with interleukin-2 (IL-2) and obtained an adequate number of metaphases. Cytogenetic analyses revealed the loss of one X chromosome as the sole cytogenetic aberration. Chromosome analysis of the corresponding blood showed a normal female karyotype. Monosomy X as the sole clonal chromosomal abnormality is found in human hematopoietic malignancies as well, thus the dog may serve as a promising animal model. Copyright © 2011 S. Karger AG, Basel.

  19. Automation of gender determination in human canines using artificial intelligence

    Directory of Open Access Journals (Sweden)

    F. Fidya

    2017-09-01

    Full Text Available Background: Gender determination is an important aspect of the identification process. The tooth represents a part of the human body that indicates the nature of sexual dimorphism. Artificial intelligence enables computers to perform to the same standard the same tasks as those carried out by humans. Several methods of classification exist within an artificial intelligence approach to identifying sexual dimorphism in canines. Purpose: This study aimed to quantify the respective accuracy of the Naive Bayes, decision tree, and multi-layer perceptron (MLP methods in identifying sexual dimorphism in canines. Methods: A sample of results derived from 100 measurements of the diameter of mesiodistal, buccolingual, and diagonal upper and lower canine jaw models of both genders were entered into an application computer program that implements the algorithm (MLP. The analytical process was conducted by the program to obtain a classification model with testing being subsequently carried out in order to obtain 50 new measurement results, 25 each for males and females. A comparative analysis was conducted on the program-generated information. Results: The accuracy rate of the Naive Bayes method was 82%, while that of the decision tree and MLP amounted to 84%. The MLP method had an absolute error value lower than that of its decision tree counterpart. Conclusion: The use of artificial intelligence methods produced a highly accurate identification process relating to the gender determination of canine teeth. The most appropriate method was the MLP with an accuracy rate of 84%.

  20. Expression and function of survivin in canine osteosarcoma.

    Science.gov (United States)

    Shoeneman, Jenette K; Ehrhart, E J; Eickhoff, Jens C; Charles, J B; Powers, Barbara E; Thamm, Douglas H

    2012-01-01

    Osteosarcoma has a high mortality rate and remains in need of more effective therapeutic approaches. Survivin is an inhibitor of apoptosis family member protein that blocks apoptosis and drives proliferation in human cancer cells where it is commonly elevated. In this study, we illustrate the superiority of a canine osteosarcoma model as a translational tool for evaluating survivin-directed therapies, owing to the striking similarities in gross and microscopic appearance, biologic behavior, gene expression, and signaling pathway alterations. Elevated survivin expression in primary canine osteosarcoma tissue correlated with increased histologic grade and mitotic index and a decreased disease-free interval (DFI). Survivin attenuation in canine osteosarcoma cells inhibited cell-cycle progression, increased apoptosis, mitotic arrest, and chemosensitivity, and cooperated with chemotherapy to significantly improve in vivo tumor control. Our findings illustrate the utility of a canine system to more accurately model human osteosarcoma and strongly suggest that survivin-directed therapies might be highly effective in its treatment. ©2011 AACR.

  1. Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Marie E. Legare, Jamie Bush, Amanda K. Ashley, Taka Kato, William H. Hanneman

    2011-01-01

    Full Text Available Canine and human osteosarcoma (OSA have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have characterized seven different OSA canine cell lines: Abrams, D17, Grey, Hughes, Ingles, Jarques, and Marisco and compared them to U2, a human OSA cell line, for the following parameters: morphology, growth, contact inhibition, migrational tendencies, alkaline phosphatase staining, heterologous tumor growth, double-strand DNA breaks, and oxidative damage. All results demonstrated the positive characteristics of the Abrams cell line for use in future studies of OSA. Of particular interest, the robust growth of a subcutaneous tumor and rapid pulmonary metastasis of the Abrams cell line in an immunocompromised mouse shows incredible potential for the future use of Abrams as a canine OSA model. Further investigations utilizing a canine cell model of OSA, such as Abrams, will be invaluable to understanding the molecular events underlying OSA, pharmaceutical inhibition of metastasis, and eventual prevention of this devastating disease.

  2. Surgical innovations in canine gonadectomy

    NARCIS (Netherlands)

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated

  3. Immunohistochemical Characterization of Canine Lymphomas

    Directory of Open Access Journals (Sweden)

    Roxana CORA

    2017-11-01

    Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

  4. Canine faecal contamination and parasitic risk in the city of Naples (southern Italy

    Directory of Open Access Journals (Sweden)

    Veneziano Vincenzo

    2006-09-01

    Full Text Available Abstract Background Dogs are associated with more than 60 zoonotic diseases among which, parasitosis and, in particular, helminthosis, can pose serious public-health concerns worldwide. Many canine gastrointestinal parasites eliminate their dispersion elements (eggs, larvae, oocysts by the faecal route. The quantity of canine faeces deposited on public and private property in cities worldwide is both a perennial nuisance and an important health issue. Public sites such as playgrounds, parks, gardens, public squares and sandpits may be an important source of human infection. The aim of this study was to evaluate the extent of both canine faecal contamination in the city of Naples (southern Italy, and presence of canine parasitic elements, with particular regard to those which are potential agents of zoonosis. A regular grid of sub-areas (1 km × 700 m was overlaid on the city map using a Geographical Information System (GIS. In each sub-area the straightest 1 km transect was drawn and digitalized on-screen in the GIS. Between February and May 2005 canine faeces were counted along the 1 km transects in 143 sub-areas, and 415 canine faecal samples were collected and submitted to coprological examinations. Negative binomial regression models and Gaussian random effects models were used to analyze the association between faeces count and human population density taking into account for extraPoisson variability. Logistic regression model was used to evaluate the association between positivity to parasitic elements and number of canine faeces. Results Out of the 143 studied sub-areas, 141 (98.6% contained canine faeces. There was a strong spatial gradient with 48% of the total variability accounted by between neighbourhood variability; a positive association between the number of faeces and the human population density was found. Seventy (over 415, 16.9% canine faecal samples were positive for parasitic elements. There was no association between

  5. Ontogeny of canine dimorphism in extant hominoids.

    Science.gov (United States)

    Schwartz, G T; Dean, C

    2001-07-01

    Many behavioral and ecological factors influence the degree of expression of canine dimorphism for different reasons. Regardless of its socioecological importance, we know virtually nothing about the processes responsible for the development of canine dimorphism. Our aim here is to describe the developmental process(es) regulating canine dimorphism in extant hominoids, using histological markers of tooth growth. Teeth preserve a permanent record of their ontogeny in the form of short- and long-period incremental markings in both enamel and dentine. We selected 52 histological sections of sexed hominoid canine teeth from a total sample of 115, from which we calculated the time and rate of cuspal enamel formation and the rate at which ameloblasts differentiate along the future enamel-dentine junction (EDJ) to the end of crown formation. Thus, we were able to reconstruct longitudinal growth curves for height attainment in male and female hominoid canines. Male hominoids consistently take longer to form canine crowns than do females (although not significantly so for our sample of Homo). Male orangutans and gorillas occasionally take up to twice as long as females to complete enamel formation. The mean ranges of female canine crown formation times are similar in Pan, Gorilla, and Pongo. Interspecific differences between female Pan canine crown heights and those of Gorilla and Pongo, which are taller, result from differences in rates of growth. Differences in canine crown heights between male Pan and the taller, more dimorphic male Gorilla and Pongo canines result both from differences in total time taken to form enamel and from faster rates of growth in Gorilla and Pongo. Although modern human canines do not emerge as significantly dimorphic in this study, it is well-known that sexual dimorphism in canine crown height exists. Larger samples of sexed modern human canines are therefore needed to identify clearly what underlies this. Copyright 2001 Wiley-Liss, Inc.

  6. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  7. One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus, and canine kobuvirus.

    Science.gov (United States)

    Liu, Dafei; Liu, Fei; Guo, Dongchun; Hu, Xiaoliang; Li, Zhijie; Li, Zhigang; Ma, Jianzhang; Liu, Chunguo

    2018-01-23

    To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10 2.1 TCID 50 for CDV, 10 1.9 TCID 50 for CPV and 10 3 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.

  8. Genetics of Human and Canine Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2015-01-01

    Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  9. Genetics of Human and Canine Dilated Cardiomyopathy.

    Science.gov (United States)

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  10. The Effect of Using Self-ligating Brackets on Maxillary Canine Retraction: A Split-mouth Design Randomized Controlled Trial.

    Science.gov (United States)

    Hassan, Siba E; Hajeer, Mohammad Y; Alali, Osama H; Kaddah, Ayham S

    2016-06-01

    The results of previous studies about the efficacy of using self-ligating brackets (SLBs) in controlling canine movement during retraction are not in harmony. Therefore, the current study aimed to compare the effects of using new passive SLBs on maxillary canine retraction with sliding mechanics vs conventional ligating brackets (CLBs) tied with metal ligatures. The sample comprised 15 adult patients (4 males, 11 females; 18-24 years) requiring bilateral extraction of maxillary first premolars. Units of randomization are the left or right maxillary canines within the same patient. The two maxillary canines in each patient were randomly assigned to one of the two groups in a simple split-mouth design. The canines in the SLBs group (n = 15) were bracketed with SLBs (Damon Q™), while the canines in the CLBs group (n = 15) were bracketed with conventional brackets (Mini Master Series). Transpalatal bars were used for anchorage. After leveling and alignment, 0.019 × 0.025" stainless steel working archwires were placed. Canines were retracted using a nickel-titanium close-coil springs with a 150 gm force. The amount and rate of maxillary canine retraction, canine rotation, and loss of anchorage were measured on study models collected at the beginning of canine retraction (T0) and 12 weeks later (T1). Differences were analyzed using paired-samples t-tests. The effect differences were statistically significant (p brackets gave better results compared to the CLBs in terms of rate of movement, amount of canine rotation following extraction, and anchorage loss.

  11. Diagnosis, prevention, and management of canine hip dysplasia: a review

    Directory of Open Access Journals (Sweden)

    Schachner ER

    2015-05-01

    Full Text Available Emma R Schachner, Mandi J Lopez Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA Abstract: Canine hip dysplasia (CHD is a polygenic and multifactorial developmental disorder characterized by coxofemoral (hip joint laxity, degeneration, and osteoarthritis (OA. Current diagnostic techniques are largely subjective measures of joint conformation performed at different stages of development. Recently, measures on three-dimensional images generated from computed tomography scans predicted the development of OA associated with CHD. Continued refinement of similar imaging methods may improve diagnostic imaging techniques to identify dogs predisposed to degenerative hip joint changes. By current consensus, joint changes consistent with CHD are influenced by genetic predisposition as well as environmental and biomechanical factors; however, despite decades of work, the relative contributions of each to the development and extent of CHD signs remain elusive. Similarly, despite considerable effort to decipher the genetic underpinnings of CHD for selective breeding programs, relevant genetic loci remain equivocal. As such, prevention of CHD within domestic canine populations is marginally successful. Conservative management is often employed to manage signs of CHD, with lifelong maintenance of body mass as one of the most promising methods. Surgical intervention is often employed to prevent joint changes or restore joint function, but there are no gold standards for either goal. To date, all CHD phenotypes are considered as a single entity in spite of recognized differences in expression and response to environmental conditions and treatment. Identification of distinct CHD phenotypes and targeting evidence-based conservative and invasive treatments for each may significantly advance prevention and management of a prevalent, debilitating condition in canine companions. Keywords: canine

  12. Emerging perspectives on hereditary glomerulopathies in canines

    Directory of Open Access Journals (Sweden)

    Littman MP

    2015-04-01

    Full Text Available Meryl P LittmanDepartment of Clinical Studies – Philadelphia, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USAAbstract: Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immune-complex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1 glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked, and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive; and 2 glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to non-synonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic

  13. The Ancient Maya Landscape: Facing the Challenges and Embracing the Promise of Integrating Archaeology, Remote Sensing, Soil Science and Hydrologic Modeling for Coupled Natural and Human Systems.

    Science.gov (United States)

    Murtha, T., Jr.; Duffy, C.; Cook, B. D.; Schroder, W.; Webster, D.; French, K. D.; Alcover, O.; Golden, C.; Balzotti, C.; Shaffer, D.

    2016-12-01

    Relying on a niche inheritance perspective, this paper discusses the long-term spatial and temporal dynamics of land-use management, agricultural decision making and patterns of resource availability in the tropical lowlands of Central America. We introduce and describe ongoing research that addresses a series of long standing questions about coupled natural and human history dynamics in the Central Maya lowlands, emphasizing the role of landscape and region to address these questions. First, we summarize the results of a CNH pilot study focused on the evolution of the regional landscape of Tikal, Guatemala. Particular attention is centered on how we integrated landscape survey, traditional archaeology and soil studies to understand the spatial and temporal dynamics of agricultural land use and intensification over a two thousand period. Additionally, we discuss how these results were integrated into remote sensing, hydrological and erosion models to better understand how past changes in available water and productive land compare to what we know about settlement patterns in the Tikal Region over that same time period. We not only describe how the Maya transformed this landscape, but also how the region influenced changing patterns of settlement and land use. We finish this section with a discussion of some of the unique challenges integrating archaeological information to study CNH dynamics during this pilot study. Second, we introduce a new project designed to `scale up' the pilot study for a macro-regional analysis of the lowland Maya landscape. The new project leverages a uniquely sampled LIDAR data set designed to refine measurements of above ground carbon storage. Our new project quantitatively examines these data for evidence for past human activity. Preliminary results offer a promising path for tightly integrating archaeology, natural science, remote sensing and modeling for studying CNH dynamics in the deep and recent past.

  14. Serotonin transporter and dopamine transporter imaging in the canine brain

    Energy Technology Data Exchange (ETDEWEB)

    Peremans, Kathelijne [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Goethals, Ingeborg [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); De Vos, Filip [Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, B-9000 Ghent (Belgium); Dobbeleir, A. [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Ham, Hamphrey [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); Van Bree, Henri [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Heeringen, Cees van [Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium); Audenaert, Kurt [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium) and Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium)]. E-mail: kurt.audenaert@ugent.be

    2006-10-15

    The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [{sup 123}I]-{beta}-CIT and [{sup 123}I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

  15. Serotonin transporter and dopamine transporter imaging in the canine brain

    International Nuclear Information System (INIS)

    Peremans, Kathelijne; Goethals, Ingeborg; De Vos, Filip; Dobbeleir, A.; Ham, Hamphrey; Van Bree, Henri; Heeringen, Cees van; Audenaert, Kurt

    2006-01-01

    The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [ 123 I]-β-CIT and [ 123 I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models

  16. Cryopreservation of microencapsulated canine sperm.

    Science.gov (United States)

    Shah, Shambhu; Otsuki, Tsubasa; Fujimura, Chika; Yamamoto, Naoki; Yamashita, Yasuhisa; Higaki, Shogo; Hishinuma, Mitsugu

    2011-03-01

    The objective was to develop a method for cryopreserving microencapsulated canine sperm. Pooled ejaculates from three beagle dogs were extended in egg yolk tris extender and encapsulated using alginate and poly-L-lysine at room temperature. The microcapsules were cooled at 4 °C, immersed in pre-cooled extender (equivalent in volume to the microcapsules) to reach final concentration of 7% (v/v) glycerol and 0.75% (v/v) Equex STM paste, and equilibrated for 5, 30 and 60 min at 4 °C. Thereafter, microcapsules were loaded into 0.5 mL plastic straws and frozen in liquid nitrogen. In Experiment 1, characteristics of microencapsulated canine sperm were evaluated after glycerol addition at 4 °C. Glycerol exposure for 5, 30 and 60 min did not significantly affect progressive motility, viability, or acrosomal integrity of microencapsulated sperm compared with pre-cooled unencapsulated sperm (control). In Experiment 2, characteristics of frozen-thawed canine microencapsulated sperm were evaluated at 0, 3, 6, and 9 h of culture at 38.5 °C. Pre-freeze glycerol exposure for 5, 30, and 60 min at 4 °C did not influence post-thaw quality in unencapsulated sperm. Post-thaw motility and acrosomal integrity of microencapsulated sperm decreased more than those of unencapsulated sperm (P < 0.05) following glycerol exposure for 5 min. However, motility, viability and acrosomal integrity of microencapsulated sperm after 30 and 60 min glycerol exposure were higher than unencapsulated sperm cultured for 6 or 9 h (P < 0.05). In conclusion, since microencapsulated canine sperm were successfully cryopreserved, this could be a viable alternative to convention sperm cryopreservation in this species. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Surgical innovations in canine gonadectomy

    OpenAIRE

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated negative consequences (lengthy placement, impaired wound healing around bulky knots, and the effect of unsightly knots on cosmetics). A study in 9 dogs found that celiotomy closure was easily achiev...

  18. Functional Characterization of the Canine Heme-Regulated eIF2α Kinase: Regulation of Protein Synthesis

    Directory of Open Access Journals (Sweden)

    Kimon C. Kanelakis

    2009-01-01

    Full Text Available The heme-regulated inhibitor (HRI negatively regulates protein synthesis by phosphorylating eukaryotic initiation factor-2α (eIF2α thereby inhibiting protein translation. The importance of HRI in regulating hemoglobin synthesis in erythroid cells makes it an attractive molecular target in need of further characterization. In this work, we have cloned and expressed the canine form of the HRI kinase. The canine nucleotide sequence has 86%, 82%, and 81% identity to the human, mouse, and rat HRI, respectively. It was noted that an isoleucine residue in the ATP binding site of human, rat, and mouse HRI is replaced by a valine in the canine kinase. The expression of canine HRI protein by in vitro translation using wheat germ lysate or in Sf9 cells using a baculovirus expression system was increased by the addition of hemin. Following purification, the canine protein was found to be 72 kD and showed kinase activity determined by its ability to phosphorylate a synthetic peptide substrate. Quercetin, a kinase inhibitor known to inhibit mouse and human HRI, inhibits canine HRI in a concentration-dependent manner. Additionally, quercetin is able to increase de novo protein synthesis in canine reticulocytes. We conclude that the canine is a suitable model species for studying the role of HRI in erythropoiesis.

  19. Promising change, delivering continuity

    DEFF Research Database (Denmark)

    Lund, Jens Friis; Sungusia, Eliezeri; Mabele, Mathew Bukhi

    2017-01-01

    REDD+ is an ambition to reduce carbon emissions from deforestation and forest degradation in the Global South. This ambition has generated unprecedented commitment of political support and financial funds for the forest-development sector. Many academics and people-centered advocacy organizations...... have conceptualized REDD+ as an example of ‘‘green grabbing” and have voiced fears of a potential global rush for land and trees. In this paper we argue that, in practice and up until now, REDD+ resembles longstanding dynamics of the development and conservation industry, where the promise of change...... becomes a discursive commodity that is constantly reproduced and used to generate value and appropriate financial resources. We thus argue for a re-conceptualization of REDD+ as a conservation fad within the broader political economy of development and conservation. We derive this argument from a study...

  20. A comparative study between mixed-type tumours from human salivary and canine mammary glands

    International Nuclear Information System (INIS)

    Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-01-01

    In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations

  1. BIM: Promises and reality

    Directory of Open Access Journals (Sweden)

    Svetel Igor

    2014-01-01

    Full Text Available The building information modeling - BIM is a technology developed toward creation of computer based information model that encompasses whole building lifecycle. Toward that goal a number of information technology standards have been developed that enable different professions in AEC to cooperatively develop electronic building model. The paper gives overview of essential technologies, discusses their intended purpose, and gives outline of the currently achieved functionality.

  2. 9 CFR 113.306 - Canine Distemper Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... distemper virus, each of five canine distemper susceptible ferrets shall be injected with a sample of the...

  3. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... canine distemper susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood...

  4. Evaluation of the Effects of Temporary Covered Nitinol Stent Placement in the Prostatic Urethra: Short-Term Study in the Canine Model

    International Nuclear Information System (INIS)

    Crisostomo, Veronica; Song, Ho Young; Maynar, Manuel; Sun, Fei; Soria, Federico; Lima, Juan Rafael; Yoon, Chang Jin; Uson-Gargallo, Jesus

    2007-01-01

    Purpose. To evaluate the effect of temporary stent placement on the canine prostatic urethra. Methods. Retrievable PTFE-covered nitinol stents were placed in the prostatic urethras of 8 beagle dogs under fluoroscopic guidance. Retrograde urethrography was obtained before and after stenting. Retrograde urethrography and endoscopy were performed 1 and 2 months after deployment. The endoscopic degree of hyperplasia was rated on a scale of 0 to 4 (0 absence, 4 = occlusion). On day 60, stents were removed and urethrography was performed immediately before euthanasia. Pathologic analysis was performed to determine the degree of glandular atrophy, periurethral fibrosis, and urethral dilation. Results. Stent deployment was technically successful in 7 animals, and failed in 1 dog due to a narrow urethral lumen. Complete migration was seen in 2 animals at 1 month, and an additional stent was deployed. On day 30, endoscopy showed slight hyperplasia (grade 1) in 3 animals. On day 60, moderate hyperplasia (grade 2) was evidenced in 4 cases. No impairment of urinary flow was seen during follow-up. Retrieval was technically easy to perform, and was successful in all dogs. The major histologic findings were chronic inflammatory cell infiltrates; prostate glandular atrophy, with a mean value of 1.86 (SD 0.90); periurethral fibrosis, with a mean ratio of 29.37 (SD 10.41); and dilatation of the prostatic urethra, with a mean ratio of 6.75 (SD 3.22). Conclusion. Temporary prostatic stent placement in dogs is safe and feasible, causing marked enlargement of the prostatic urethral lumen. Retrievable covered stents may therefore be an option for bladder outlet obstruction management in men

  5. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

    Directory of Open Access Journals (Sweden)

    Corey Saba

    Full Text Available Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV. Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within

  6. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

    Science.gov (United States)

    Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

    2018-02-01

    IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

  7. Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects the Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from disproportionate short stature dwarfism of varying severity. Through a genome-wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42×10(-6, pgenome-wide = 0.013. The associated locus contained a promising candidate gene, cartilage specific integrin alpha 10 (ITGA10, and mutation screening of its 30 exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695* that segregated fully with the disease in both breeds (p = 2.5×10(-23. A 24% mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The ITGA10 gene product, integrin receptor α10-subunit combines into a collagen-binding α10β1 integrin receptor, which is expressed in cartilage chondrocytes and mediates chondrocyte-matrix interactions during endochondral ossification. As a consequence of the nonsense mutation, the α10-protein was not detected in the affected cartilage tissue. The canine phenotype highlights the importance of the α10β1 integrin in bone growth, and the large animal model could be utilized to further delineate its specific functions. Finally, this study revealed a candidate gene for human chondrodysplasias and enabled the development of a genetic test for breeding purposes to eradicate the disease from the two dog breeds.

  8. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu

    2015-06-01

    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  9. Canine scent detection of canine cancer: a feasibility study

    Directory of Open Access Journals (Sweden)

    Dorman DC

    2017-10-01

    Full Text Available David C Dorman,1 Melanie L Foster,2 Katherine E Fernhoff,1 Paul R Hess2 1Department of Molecular and Biomedical Sciences, 2Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA Abstract: The scent detection prowess of dogs has prompted interest in their ability to detect cancer. The purpose of this study was to determine whether dogs could use olfactory cues to discriminate urine samples collected from dogs that did or did not have urinary tract transitional cell carcinoma (TCC, at a rate greater than chance. Dogs with previous scent training (n=4 were initially trained to distinguish between a single control and a single TCC-positive urine sample. All dogs acquired this task (mean =15±7.9 sessions; 20 trials/session. The next training phase used four additional control urine samples (n=5 while maintaining the one original TCC-positive urine sample. All dogs quickly acquired this task (mean =5.3±1.5 sessions. The last training phase used multiple control (n=4 and TCC-positive (n=6 urine samples to promote categorical training by the dogs. Only one dog was able to correctly distinguish multiple combinations of TCC-positive and control urine samples suggesting that it mastered categorical learning. The final study phase evaluated whether this dog would generalize this behavior to novel urine samples. However, during double-blind tests using two novel TCC-positive and six novel TCC-negative urine samples, this dog did not indicate canine TCC-positive cancer samples more frequently than expected by chance. Our study illustrates the need to consider canine olfactory memory and the use of double-blind methods to avoid erroneous conclusions regarding the ability of dogs to alert on specimens from canine cancer patients. Our results also suggest that sample storage, confounding odors, and other factors need to be considered in the design of future studies that evaluate the detection of

  10. New and emerging pathogens in canine infectious respiratory disease.

    Science.gov (United States)

    Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

    2014-03-01

    Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

  11. Genetic diversity of canine olfactory receptors

    Directory of Open Access Journals (Sweden)

    Hitte Christophe

    2009-01-01

    Full Text Available Abstract Background Evolution has resulted in large repertoires of olfactory receptor (OR genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations. Results We sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47% of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently. Conclusion Our demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of

  12. Concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.

    Science.gov (United States)

    Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Fritzen, Juliana Torres Tomazi; Garcia, João Luis; Weissenböck, Herbert; da Silva, Ana Paula; Bodnar, Livia; Okano, Werner; Alfieri, Alice Fernandes

    2013-01-01

    The concomitant infections of Canine distemper virus (CDV), Canine adenovirus A types 1 (CAdV-1) and 2 (CAdV-2), Canine parvovirus type 2 (CPV-2), and Toxoplasma gondii are described in a 43-day-old mixed-breed puppy. Clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for T. gondii, also died. Necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid tissue, non-collapsible lungs, congestion of meningeal vessels, and a pale area in the myocardium. Histopathology demonstrated necrotizing myocarditis associated with intralesional apicomplexan protozoa; necrotizing and chronic hepatitis associated with rare intranuclear inclusion bodies within hepatocytes; necrotizing bronchitis and bronchiolitis; interstitial pneumonia associated with eosinophilic intracytoplasmic inclusion bodies within epithelial cells; atrophy and fusion of intestinal villi with cryptal necrosis; and white matter demyelination of the cerebrum and cerebellum associated with intranuclear inclusion bodies within astrocytes. Polymerase chain reaction (PCR) amplified the partial fragments (bp) of the CDV N gene (290 bp), CPV-2c VP2 capsid protein gene (583 bp), and CAdV-1 (508 bp) and CAdV-2 (1,030 bp) E gene from urine and tissue samples. The PCR assays demonstrated that the apicomplexan protozoa observed within several organs contained DNA specific for T. gondii; genotyping revealed T. gondii type III. The findings support the characterization of concomitant infections of CDV, CAdV-1, CAdV-2, CPV-2, and T. gondii in this puppy. Further, seroreactivity to T. gondii of the dam in association with the systemic disease observed in the puppy described herein is suggestive of congenital toxoplasmosis.

  13. Effects of the canine rattlesnake vaccine in moderate to severe cases of canine crotalid envenomation

    Directory of Open Access Journals (Sweden)

    Leonard MJ

    2014-10-01

    Full Text Available McGee J Leonard,1 Catherine Bresee,2 Andrew Cruikshank1 1Animal Specialty and Emergency Center, Los Angeles, CA, USA; 2The Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: This is a retrospective multicenter study (2006–2012 examining a population of dogs with moderate to severe crotalid envenomation for protective effects of the canine rattlesnake vaccine. Five nonacademic emergency and referral veterinary hospitals in Southern California were involved in the study and contributed records regarding a total of 82 client-owned dogs that were treated for naturally occurring rattlesnake envenomation. All dogs received antivenin (Crotalidae polyvalent, with dosages ranging from one to three vials (mean: 1.3±0.6. Fourteen dogs (17% had a history of prior vaccination against crotalid venom. In univariate logistic regression modeling, cases with lower body weight (P=0.0001 or higher snakebite severity scores (P<0.0001 were associated with greater morbidity. No statistically significant difference in morbidity or mortality between vaccinated and unvaccinated dogs was found. The findings of this study did not identify a significantly protective effect of previous vaccination in the cases of moderate to severe rattlesnake envenomation that require treatment with antivenin. Keywords: rattlesnake envenomation, vaccine, antivenin, canine

  14. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Tuttle, W.C.; Slauson, D.O.; Dahlstrom, M.; Gorman, C.

    1974-01-01

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

  15. Military veterans and canine assistance for post-traumatic stress disorder: A narrative review of the literature.

    Science.gov (United States)

    Krause-Parello, Cheryl A; Sarni, Sarah; Padden, Eleni

    2016-12-01

    Veterans with post-traumatic stress disorder (PTSD) are a vulnerable population at high risk for depression, isolation, and suicide. A substantial body of anecdotal evidence exists supporting the use of canines as an effective adjunct treatment for this population. However, a comprehensive review of its use based on scientific literature has thus far not been conducted. A narrative literature review was conducted to examine the current state of the science on canine assistance for veterans diagnosed with PTSD in order to synthesize current empirical knowledge on the subject. Articles were retrieved among the small body of recent literature using computerized database searches. Inclusion criteria included peer-reviewed journal publications published through October 1st, 2015. Only originally published articles that examined the outcomes of canine assistance on veterans with PTSD were examined. Additionally, each included article was specific to veterans, dogs, and, PTSD in combination rather than article that discuss the concepts separately. Exclusion criteria included symposia and conference material, dissertations, media articles, and no mention of canines as a treatment modality. 563 articles were retrieved; 6 met the criteria. When evaluating data, information and themes were extracted into an Excel table; this table was employed in the synthesis of information into manuscript form. The following themes were explored within the selected publications: What is Canine Assistance; Why Use Canine Assistance for PTSD in Veterans; Concerns; and Future Directions. The literature endorsed canine assistance for PTSD in veterans as a promising modality. Authors also raised concerns about lack of protocols, cost and availability barriers, and animal welfare calling for additional, rigorous research to advance its use as a treatment for veterans with PTSD. PTSD continues to pose significant psychological, health, and welfare challenges to veterans and the multi

  16. Changes of red blood cell aggregation parameters in a long-term follow-up of splenectomy, spleen-autotransplantation and partial or subtotal spleen resections in a canine model.

    Science.gov (United States)

    Miko, Iren; Nemeth, Norbert; Peto, Katalin; Furka, Andrea; Toth, Laszlo; Furka, Istvan

    2017-01-01

    Decrease or loss in splenic filtration function may influence the hemorheological state. To follow-up the long-term effects of splenectomy, spleen autotransplantation and spleen resections on red blood cell aggregation in a canine model. Beagle dogs were subjected to control (n = 6), splenectomy (SE, n = 4), spleen autotransplantation (AU, Furka's spleen-chip method, n = 8) or partial and subtotal spleen resection (n = 4/each) groups, and followed-up for 18 postoperative (p.o.) months. Erythrocyte aggregation was determined in parallel by light-transmittance aggregometry (Myrenne MA-1 aggregometer) and syllectometry (LoRRca). Erythrocyte aggregation decreased three months after splenectomy, with lower aggregation index and elongated aggregation time. It was more or less associated with relatively lower hematocrit and fibrinogen concentration. However, in autotransplantated animals a relatively higher fibrinogen did not increase the aggregation markedly. Spleen resection resulted in the most controversial red blood cell aggregation findings, and it seems, that the degree of the resection is an influencing factor. Splenectomy alters erythrocyte aggregation, spleen autotransplantation can be useful to preserve filtration function. However, the degree of restoration shows individual differences with a kind of 'functional periodicity'. Spleen resection controversially influences erythrocyte aggregation parameters. The subtotal resection is supposed to be worse than spleen autotransplantation.

  17. Vaccines: an ongoing promise?

    Science.gov (United States)

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  18. Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies

    OpenAIRE

    J. Van Heerden; J. Bingham; M. Van Vuuren; R.E.J. Burroughs; E. Stylianides

    2002-01-01

    Wild dogs Lycaon pictus (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use ...

  19. Radioimmunoassay of canine growth hormone

    International Nuclear Information System (INIS)

    Eigenmann, J.E.; Eigenmann, R.Y.

    1981-01-01

    A sensitive radioimmunoassay (RIA) for canine growth hormone (GH) was developed. Antibodies were elicited in rhesus monkeys. One antiserum exhibited a working titer at a dilution of 1:500 000. Radioiodination was performed enzymatically employing lactoperoxidase. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.39 and 50 ng/ml. Formation of large-molecular [ 125 I]GH during storage caused diminished assay sensitivity. Therefore [ 125 I]GH was re-purified by gel chromatography. Using this procedure, high and reproducible assay sensitivity was obtained. Tracer preparations were used for as long as 3 months after iodination. Diluted plasma from normal and acromegalic dogs resulted in a dose-response curve parallel to the standard curve. Canine prolactin exhibited a cross-reactivity of 2%. The within-assay coefficient of variation (CV) was 3.8 and the between-assay CV was 7.2%. Mean plasma GH concentration in normal dogs was 1.92 +- 0.14 ng/ml (mean +- SEM.) GH levels in acromegalic dogs were appreciably higher. Insulin-induced hypoglycaemia, arginine and ornithine administration resulted in inconsistent and sluggish GH increment. A better response was obtained by injecting a low dose of clonidine. Clonidine administration to hypopituitary dogs resulted in absent or poor GH increment. (author)

  20. The Promises of Biology and the Biology of Promises

    DEFF Research Database (Denmark)

    Lee, Jieun

    2015-01-01

    commitments with differently imagined futures. I argue that promises are constitutive of the stem cell biology, rather than being derivative of it. Since the biological concept of stem cells is predicated on the future that they promise, the biological life of stem cells is inextricably intertwined...... patients’ bodies in anticipation of materializing the promises of stem cell biology, they are produced as a new form of biovaluable. The promises of biology move beyond the closed circuit of scientific knowledge production, and proliferate in the speculative marketplaces of promises. Part II looks at how...... of technologized biology and biological time can appear promising with the backdrop of the imagined intransigence of social, political, and economic order in the Korean society....

  1. MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lopez

    Full Text Available Osteosarcoma (OSA is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease.RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes.These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

  2. MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

    Science.gov (United States)

    Lopez, Cecilia M; Yu, Peter Y; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A; Fenger, Joelle M

    2018-01-01

    Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

  3. Epidemiology of canine gastrointestinal helminths in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Nozyechi Ngulube Chidumayo

    2018-02-01

    Full Text Available Abstract Background Dogs have a close association with humans providing companionship, security and a source of dietary protein. However, dogs are also potential carriers of zoonotic pathogens. Dogs, therefore, pose a public health risk and a good understanding of canine diseases is important for planning and implementing control measures. The aim of this study was to characterise canine helminthiasis in sub-Saharan Africa using a systematic approach. Methods Pubmed and Google Scholar were searched for relevant primary studies published from 2000. Forty-one eligible studies were included in the meta-analysis. Pooled prevalences were estimated using the quality effects model. Results and conclusions Twenty-six genera of enteric helminths were reported and the pooled estimate of canine helminthiasis was 71% (95% CI: 63–79%. Species of Ancylostoma and Toxocara, causative agents of larva migrans in humans, were the most frequently reported helminths with pooled estimated prevalences of 41% (95% CI: 32–50% and 22% (95% CI: 16–29%, respectively. Dipylidium caninum and Taenia spp. were the most frequently reported cestodes with pooled estimated prevalences of 20% (95% CI: 12–29% and 9% (95% CI: 5–15%, respectively. Trematodes were rarely reported. There was a high level of heterogeneity in most pooled estimates (I2 ˃ 80%. The results of this study show that canine helminthiasis is highly prevalent in sub-Saharan Africa and there is need for regular deworming programmes to improve the health status of the dogs and minimise the potential health risk to humans.

  4. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology.

    Science.gov (United States)

    Fenger, Joelle M; London, Cheryl A; Kisseberth, William C

    2014-01-01

    Osteosarcoma (OSA) is the most common form of malignant bone cancer in children and dogs, although the disease occurs in dogs approximately 10 times more frequently than in people. Multidrug chemotherapy and aggressive surgical techniques have improved survival; however, new therapies for OSA are critical, as little improvement in survival times has been achieved in either dogs or people over the past 15 years, even with significant efforts directed at the incorporation of novel therapeutic approaches. Both clinical and molecular evidence suggests that human and canine OSA share many key features, including tumor location, presence of microscopic metastatic disease at diagnosis, development of chemotherapy-resistant metastases, and altered expression/activation of several proteins (e.g. Met, ezrin, phosphatase and tensin homolog, signal transducer and activator of transcription 3), and p53 mutations, among others. Additionally, canine and pediatric OSA exhibit overlapping transcriptional profiles and shared DNA copy number aberrations, supporting the notion that these diseases are similar at the molecular level. This review will discuss the similarities between pediatric and canine OSA with regard to histology, biologic behavior, and molecular genetic alterations that indicate canine OSA is a relevant, spontaneous, large animal model of the pediatric disease and outline how the study of naturally occurring OSA in dogs will offer additional insights into the biology and future treatment of this disease in both children and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. BNCT of canine osteosarcoma

    International Nuclear Information System (INIS)

    Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.

    2006-01-01

    A dog was diagnosed with osteosarcoma (8x6x5cm) in the right wing of ilium by radiography, radionuclide scintigraphy and histological study of biopsy material. The treatment plan was as follows: γ-therapy in combination with chemotherapy; prevention of hematogenous pulmonary metastases by the transfusion of 130 ml of allogenic marrow from a healthy donor; administration of 11.4g 10 B-boronphenylalanine into the right iliac artery; resection of the right iliac wing with the osteosarcoma lesion; neutron irradiation (MEPhI Reactor) of the bone fragment (dose on healthy osteocytes - 15±4 Gy (W), on tumor - 50±9 Gy (W); reimplantation and fixation of the fragment; three courses of adjuvant chemotherapy. The doses were determined in full-scale calculations of the reactor radiation fields with a model of the bone under the code RADUGA. The 10 B concentration (μg/g) in the bone was: normal tissue - 9±3, tumor - 28±5. In 24 hours post operation the dog was able to walk using the treated limb, and 6 months later it moved freely. The patient has been under observation for 30 months. The results of the research demonstrate complete cure. The use of similar treatment plans improves the therapeutic efficiency of BNCT. (author)

  6. Extrusion processing : effects on dry canine diets

    NARCIS (Netherlands)

    Tran, Q.D.

    2008-01-01

    Keywords: Extrusion, Canine diet, Protein, Lysine, Starch gelatinization, Palatability, Drying.

    Extrusion cooking is a useful and economical tool for processing animal feed. This high temperature, short time processing technology causes chemical and physical changes that alter the

  7. Cyclooxygenase expression in canine platelets and Madin-Darby canine kidney cells.

    Science.gov (United States)

    Kay-Mugford, P A; Benn, S J; LaMarre, J; Conlon, P D

    2000-12-01

    To examine cyclooxygenase (COX) expression in canine platelets and Madin-Darby canine kidney (MDCK) cells in culture. Canine platelets and MDCK cells. Total RNA was recovered from isolated canine platelets and MDCK cells. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), using complementary DNA probes and primers designed from the human COX sequences, were used to determine COX-1 and -2 (cyclooxygenase isoforms 1 and 2) messenger RNA (mRNA) expression. Following northern blot analysis, canine platelets were found to express only the 2.8-kb COX-1 transcript; COX-2 was not detected. Canine MDCK cells expressed the 4.5-kb COX-2 transcript, in addition to the 2.8-kb COX-1 transcript. A single DNA band of 270 base pairs was identified following gel electrophoresis of the product obtained from RT-PCR of mRNA from canine platelets. Sequencing revealed that this PCR product was 90% homologous to a portion of the human COX-1 gene (Genbank M59979). Detection of COX-1 by RT-PCR of RNA obtained from canine platelets is a novel finding. The 90% homology of the PCR product with the human sequence suggests strong conservation between the canine and human COX-1 gene. Cloning and sequencing of the canine gene will be required to fully characterize homologous regions. Because of the importance of COX in the inflammatory process and as a potential target of currently available nonsteroidal anti-inflammatory drugs (NSAID), a better understanding of canine COX may improve our ability to use NSAID appropriately, achieve efficacy, and avoid potential adverse drug effects in dogs.

  8. Comparative photoelastic study of dental and skeletal anchorages in the canine retraction

    Directory of Open Access Journals (Sweden)

    Cristiane Aparecida de Assis Claro

    2014-01-01

    Full Text Available OBJECTIVE: To compare dental and skeletal anchorages in mandibular canine retraction by means of a stress distribution analysis. METHODS: A photoelastic model was produced from second molar to canine, without the first premolar, and mandibular canine retraction was simulated by a rubber band tied to two types of anchorage: dental anchorage, in the first molar attached to adjacent teeth, and skeletal anchorage with a hook simulating the mini-implant. The forces were applied 10 times and observed in a circular polariscope. The stresses located in the mandibular canine were recorded in 7 regions. The Mann-Whitney test was employed to compare the stress in each region and between both anchorage systems. The stresses in the mandibular canine periradicular regions were compared by the Kruskal-Wallis test. RESULTS: Stresses were similar in the cervical region and the middle third. In the apical third, the stresses associated with skeletal anchorage were higher than the stresses associated with dental anchorage. The results of the Kruskal-Wallis test showed that the highest stresses were identified in the cervical-distal, apical-distal, and apex regions with the use of dental anchorage, and in the apical-distal, apical-mesial, cervical-distal, and apex regions with the use of skeletal anchorage. CONCLUSIONS: The use of skeletal anchorage in canine retraction caused greater stress in the apical third than the use of dental anchorage, which indicates an intrusive component resulting from the direction of the force due to the position of the mini-implant and the bracket hook of the canine.

  9. Varied clinico-radiological presentations of transmigrated canines

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    Ishita Gupta

    2015-01-01

    Full Text Available Canine is one of the most commonly impacted teeth in the dental arch. An unerupted permanent canine crossing the midline is called transmigration and is an unusual event. We report nine cases of impacted canine transmigration. Maxillary canine transmigration, bilateral transmigration, and transmigration associated with odontoma are rare presentations. This article discusses the varied clinico-radiologic presentations, etiology, and treatment options of transmigration. It also emphasizes the importance of panoramic radiographs for evaluation of over-retained deciduous canines or missing permanent canines.

  10. Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

    Science.gov (United States)

    Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

    2014-12-01

    A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

  11. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

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    Mehdi Hayat Shahi

    Full Text Available BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA. Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17 expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

  12. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

    Science.gov (United States)

    Shahi, Mehdi Hayat; York, Daniel; Gandour-Edwards, Regina; Withers, Sita S; Holt, Roseline; Rebhun, Robert B

    2015-01-01

    BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

  13. Canine babesiosis: from molecular taxonomy to control

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    Irwin Peter J

    2009-03-01

    Full Text Available Abstract Canine babesiosis is a clinically significant emerging vector-borne disease caused by protozoan haemoparasites. This review article considers recent literature pertaining to the taxonomic classification of Babesia and Theileria species affecting dogs and the geographical distribution of these parasites. The diagnosis of canine babesiosis by traditional, molecular and serological methods is reviewed, together with recent advances in our understanding of the pathophysiology of piroplasmosis, and of the treatment and prevention of this disease.

  14. [Nonsurgical endodontic treatment of an invaginated canine].

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    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment.

  15. Treatment modalities of palatal impacted canines

    OpenAIRE

    Dimova, Cena; Papakoca, Kiro; Ristoska, Sonja; Kovacevska, Ivona

    2012-01-01

    Introduction: The orthodontic treatment of impacted maxillary canine remains a challenge to today’s clinicians. The treatment of this clinical entity usually involves surgical exposure of the impacted tooth, followed by orthodontic traction to guide and align it into the dental arch. The impacted palatal canine requires a combination of both treatment modalities: orthodontic management and oral surgical treatment. Two types of approach are commonly used: simple exposure, or exposure with brac...

  16. Orthodontic Traction of Impacted Canine Using Cantilever

    OpenAIRE

    Nakandakari, Cláudia; Gonçalves, João Roberto; Cassano, Daniel Serra; Raveli, Taísa Boamorte; Bianchi, Jonas; Raveli, Dirceu Barnabé

    2016-01-01

    The impaction of the maxillary canines causes relevant aesthetic and functional problems. The multidisciplinary approach to the proper planning and execution of orthodontic traction of the element in question is essential. Many strategies are cited in the literature; among them is the good biomechanical control in order to avoid possible side effects. The aim of this paper is to present a case report in which a superior canine impacted by palatine was pulled out with the aid of the cantilever...

  17. Biochemical characterization of prostate-specific membrane antigen from canine prostate carcinoma cells.

    Science.gov (United States)

    Wu, Lisa Y; Johnson, Jacqueline M; Simmons, Jessica K; Mendes, Desiree E; Geruntho, Jonathan J; Liu, Tiancheng; Dirksen, Wessel P; Rosol, Thomas J; Davis, William C; Berkman, Clifford E

    2014-05-01

    Prostate-specific membrane antigen (PSMA) remains an important target for diagnostic and therapeutic application for human prostate cancer. Model cell lines have been recently developed to study canine prostate cancer but their PSMA expression and enzymatic activity have not been elucidated. The present study was focused on determining PSMA expression in these model canine cell lines and the use of fluorescent small-molecule enzyme inhibitors to detect canine PSMA expression by flow cytometry. Western blot and RT-PCR were used to determine the transcriptional and translational expression of PSMA on the canine cell lines Leo and Ace-1. An endpoint HPLC-based assay was used to monitor the enzymatic activity of canine PSMA and the potency of enzyme inhibitors. Flow cytometry was used to detect the PSMA expressed on Leo and Ace-1 cells using a fluorescently tagged PSMA enzyme inhibitor. Canine PSMA expression on the Leo cell line was confirmed by Western blot and RT-PCR, the enzyme activity, and flow cytometry. Kinetic parameters Km and Vmax of PSMA enzymatic activity for the synthetic substrate (PABGγG) were determined to be 393 nM and 220 pmol min(-1)  mg protein(-1) , respectively. The inhibitor core 1 and fluorescent inhibitor 2 were found to be potent reversible inhibitors (IC50  = 13.2 and 1.6 nM, respectively) of PSMA expressed on the Leo cell line. Fluorescent labeling of Leo cells demonstrated that the fluorescent PSMA inhibitor 2 can be used for the detection of PSMA-positive canine prostate tumor cells. Expression of PSMA on Ace-1 was low and not detectable by flow cytometry. The results described herein have demonstrated that PSMA is expressed on canine prostate tumor cells and exhibits similar enzymatic characteristics as human PSMA. The findings show that the small molecule enzyme inhibitors currently being studied for use in diagnosis and therapy of human prostate cancer can also be extended to include canine prostate cancer. Importantly

  18. The immunotherapy of canine osteosarcoma: a historical and systematic review.

    Science.gov (United States)

    Wycislo, K L; Fan, T M

    2015-01-01

    Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high-grade osteosarcoma have not changed in the past 20 years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for delaying metastatic progression with cytotoxic agents, exploration of alterative adjuvant therapies for improving management of osteosarcoma micrometastases is clinically justified. Evidence suggests that osteosarcoma is an immunogenic tumor, and development of immunotherapies for the treatment of microscopic lung metastases might improve long-term outcomes. In this review, the history and foundational knowledge of immune interactions to canine osteosarcoma are highlighted. In parallel, immunotherapeutic strategies that have been explored for the treatment of canine osteosarcoma are summarized. With a greater understanding and awareness for how the immune system might be redirected toward combating osteosarcoma metastases, the rational development of diverse immune strategies for managing osteosarcoma holds substantial promise for transforming the therapeutic landscape and improving disease management in both dogs and human beings. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  19. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  20. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Science.gov (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  1. Clinical and Statistical Study on Canine Impaction

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    Adina-Simona Coșarcă

    2013-08-01

    Full Text Available Aim: The aim of this study was to perform a clinical and statistical research on permanent impacted canine patients among those with dental impaction referred to and treated at the Oral and Maxillo-Facial Surgery Clinic of Tîrgu Mureș, over a four years period (2009-2012. Materials and methods: The study included 858 patients having dental impaction, and upon clinical records, different parameters, like frequency, gender, age, quadrant involvement, patient residence, associated complications, referring specialist and type of treatment, related to canine impaction, were assessed. Results: The study revealed: about 10% frequency of canine impaction among dental impactions; more frequent in women, in the first quadrant (tooth 13; most cases diagnosed between the age of 10-19 years; patients under 20 were referred by an orthodontist, those over 20 by a dentist; surgical exposure was more often performed than odontectomy. Conclusions: Canine impaction is the second-most frequent dental impaction in dental arch after third molars; it occurs especially in women. Due to its important role, canine recovery within dental arch is a goal to be achieved, whenever possible. Therefore, diagnose and treatment of canine impaction requires an interdisciplinary approach (surgical and orthodontic