WorldWideScience

Sample records for improved animal models

  1. Animal models to improve our understanding and treatment of suicidal behavior

    Science.gov (United States)

    Gould, T D; Georgiou, P; Brenner, L A; Brundin, L; Can, A; Courtet, P; Donaldson, Z R; Dwivedi, Y; Guillaume, S; Gottesman, I I; Kanekar, S; Lowry, C A; Renshaw, P F; Rujescu, D; Smith, E G; Turecki, G; Zanos, P; Zarate, C A; Zunszain, P A; Postolache, T T

    2017-01-01

    Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic–pituitary–adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio. PMID:28398339

  2. Opportunities for improving animal welfare in rodent models of epilepsy and seizures.

    Science.gov (United States)

    Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J

    2016-02-15

    Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Evaluation of animal models of neurobehavioral disorders

    Directory of Open Access Journals (Sweden)

    Nordquist Rebecca E

    2009-02-01

    that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s of a model and by defining better evaluation criteria, based on the proposed use of the model.

  4. Improved Variational Guiding of Smoke Animations

    DEFF Research Database (Denmark)

    Nielsen, Michael Bang; Christensen, Brian Bunch

    2010-01-01

    Smoke animations are hard to art-direct because simple changes in parameters such as simulation resolution often lead to unpredictable changes in the final result. Previous work has addressed this problem with a guiding approach which couples low-resolution simulations - that exhibit the desired......, and employing time-dependent guiding is expensive because the matrix of the resulting set of equations needs to be recomputed at every iteration. We propose an improved mathematical model for Eulerianbased simulations which is better suited for dynamic, time-dependent guiding of smoke animations through a novel...

  5. Animal Models of Chemotherapy-induced Mucositis

    DEFF Research Database (Denmark)

    Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko

    2018-01-01

    constitution). Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g. milk fractions...... easier make clinically-relevant treatment regimens possible. In synergy, animal models improve the basic pathophysiological understanding of CIM and provide new ideas for treatment that are required to make competent decisions in clinical practice....

  6. What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.

    Science.gov (United States)

    Herati, Ramin Sedaghat; Wherry, E John

    2018-04-02

    Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Animal Models of Calcific Aortic Valve Disease

    Directory of Open Access Journals (Sweden)

    Krista L. Sider

    2011-01-01

    Full Text Available Calcific aortic valve disease (CAVD, once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

  8. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

  9. Animal models of cardiovascular diseases.

    Science.gov (United States)

    Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus

    2011-01-01

    Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

  10. Research on improving animal nutrition

    International Nuclear Information System (INIS)

    Ranjhan, S.K.

    1977-01-01

    With a view to improve animal nutrition, studies have been carried out on the utilization of animal feeds using radioisotopes. Improvement of the nutritive value of straws, digestibility and VFA production by alkali treatment and other treatments has been studied by injecting VFA labelled with C 14 and H 3 . Microbial protein synthesis rates in ruminants were studied using C 14 and S 35 labelled mixed culture of bacterial protozca. Results obtained are helpful in understanding the metabolism in rumens and the microbial proteins available to the host animals on various dietary regimen. (A.K.)

  11. Towards ethically improved animal experimentation in the study of animal reproduction.

    Science.gov (United States)

    Blache, D; Martin, G B; Maloney, S K

    2008-07-01

    The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

  12. An improved mounting device for attaching intracranial probes in large animal models.

    Science.gov (United States)

    Dunster, Kimble R

    2015-12-01

    The rigid support of intracranial probes can be difficult when using animal models, as mounting devices suitable for the probes are either not available, or designed for human use and not suitable in animal skulls. A cheap and reliable mounting device for securing intracranial probes in large animal models is described. Using commonly available clinical consumables, a universal mounting device for securing intracranial probes to the skull of large animals was developed and tested. A simply made mounting device to hold a variety of probes from 500 μm to 1.3 mm in diameter to the skull was developed. The device was used to hold probes to the skulls of sheep for up to 18 h. No adhesives or cements were used. The described device provides a reliable method of securing probes to the skull of animals.

  13. Animal Models of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Carlos Zaragoza

    2011-01-01

    Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

  14. The necessity of animal models in pain research.

    Science.gov (United States)

    Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

    2010-10-01

    There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  16. Using Computational and Mechanical Models to Study Animal Locomotion

    OpenAIRE

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas

    2012-01-01

    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locom...

  17. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

    The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

  18. Animation of 3D Model of Human Head

    Directory of Open Access Journals (Sweden)

    V. Michalcin

    2007-04-01

    Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.

  19. Lanchester's attrition models and fights among social animals

    OpenAIRE

    Eldridge S. Adams; Michael Mesterton-Gibbons

    2003-01-01

    Lanchester's models of attrition during warfare have served as the basis for several predictions about conflicts between groups of animals. These models and their extensions describe rates of mortality during battles as functions of the number and fighting abilities of individuals in each group, allowing analysis of the determinants of group strength and of the cumulative numbers of casualties. We propose modifications to Lanchester's models to improve their applicability to social animals. I...

  20. Basic mechanisms of MCD in animal models.

    Science.gov (United States)

    Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

    2009-09-01

    Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

  1. Animal models of binge drinking, current challenges to improve face validity.

    Science.gov (United States)

    Jeanblanc, Jérôme; Rolland, Benjamin; Gierski, Fabien; Martinetti, Margaret P; Naassila, Mickael

    2018-05-05

    Binge drinking (BD), i.e., consuming a large amount of alcohol in a short period of time, is an increasing public health issue. Though no clear definition has been adopted worldwide the speed of drinking seems to be a keystone of this behavior. Developing relevant animal models of BD is a priority for gaining a better characterization of the neurobiological and psychobiological mechanisms underlying this dangerous and harmful behavior. Until recently, preclinical research on BD has been conducted mostly using forced administration of alcohol, but more recent studies used scheduled access to alcohol, to model more voluntary excessive intakes, and to achieve signs of intoxications that mimic the human behavior. The main challenges for future research are discussed regarding the need of good face validity, construct validity and predictive validity of animal models of BD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Improving animal productivity by nuclear techniques

    International Nuclear Information System (INIS)

    Garcia, M.; Jayasuriya, M.C.N.; Perera, B.M.A.O.

    1995-01-01

    The IAEA and FAO have run a joint programme for 30 years to assist national agricultural research systems in member states to develop, test and apply nuclear and related techniques for improving the productivity of livestock. Applications of nuclear technologies for improving livestock productivity include: use of radioimmunoassay in animal nutrition researches, animal production, and evaluating feeding and management systems through reproductive performance in a field. Geographic coverage and the type of livestock studies are: grazing animals (cattle, goats and sheep) in Africa, Latin America and Asia, as well as buffalo production in Asia. 6 refs, 8 figs, 6 tabs

  3. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

  4. The research methods and model of protein turnover in animal

    International Nuclear Information System (INIS)

    Wu Xilin; Yang Feng

    2002-01-01

    The author discussed the concept and research methods of protein turnover in animal body. The existing problems and the research results of animal protein turnover in recent years were presented. Meanwhile, the measures to improve the models of animal protein turnover were analyzed

  5. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-09-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

  6. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  7. Animal models of obesity and diabetes mellitus

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M

    2018-01-01

    More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover......, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

  8. New technologies and animal improvement

    International Nuclear Information System (INIS)

    Land, R.B.

    1988-01-01

    The simplification of genetic selection to the pragmatic choice of an appropriate base population, together with the adoption of such techniques as multiple ovulation and embryo transfer to accelerate the rate of response within the chosen population, would increase the contribution of genetic methods to the improvement of the performance of domestic animals. This is particularly relevant to developing countries where limited funds may constrain the opportunities for husbandry improvement, where it is important to select animals under the local conditions and where the infrastructure might limit the use of extensive programmes such as those based on progeny testing. (author). 5 refs, 1 tab

  9. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    OpenAIRE

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

  10. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

    This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

  11. Modelling Farm Animal Welfare

    Science.gov (United States)

    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

    Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

  12. How can economists help to improve animal welfare?

    DEFF Research Database (Denmark)

    Christensen, Tove; Lawrence, A.; Lund, Mogens

    2012-01-01

    To-date, the dominant approach to improving farm animal welfare has consisted of a combination of voluntary improvements undertaken by farmers and the tightening of legal requirements. However, history suggests that there is a limit to the improvements capable of being secured by this approach...... priorities as to which aspects of animal welfare should be promoted. Here, economic approaches can be used to capture and synthesise the perspectives of all the stakeholders, including the animals, in a transparent and systematic way. The second way is by helping to ensure that incentives are set up...... in the right way. Where the benefits and costs of improving animal welfare are initially distributed unevenly across stakeholders so that a socially desirable situation will not develop automatically, or be implemented, suitable economic principles may help to create incentives which correct this situation...

  13. Models of breast cancer: quo vadis, animal modeling?

    International Nuclear Information System (INIS)

    Wagner, Kay-Uwe

    2004-01-01

    Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease

  14. Animal Models of Diabetes Mellitus for Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Naoaki Sakata

    2012-01-01

    Full Text Available Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM: models induced by drugs including streptozotocin (STZ, pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.

  15. Animal Models of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2014-12-01

    Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

  16. Improved animal welfare, the right technology and increased business.

    Science.gov (United States)

    Støier, S; Larsen, H D; Aaslyng, M D; Lykke, L

    2016-10-01

    Animal welfare is receiving increasing attention from the authorities, the public and NGOs. For this reason, the improvement of animal welfare and animal handling systems is of the utmost importance for the meat industry. Technological developments have led to more animal friendly systems that handle animals on the day of slaughter, and these developments will be even more important as consideration for animal welfare and sustainability is no longer just a trend but a licence to operate. Improvement of animal welfare also leads to a higher value of the carcasses due to higher product quality, less cut-off caused by fewer injuries, and reduced working load, which leads to increased business opportunities. Therefore, good animal welfare is good business, and the development and implementation of new technology is the way to obtain improved animal welfare. These subjects will be addressed using examples and cases from the pork and broiler production industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Animal welfare and use of silkworm as a model animal.

    Science.gov (United States)

    Sekimizu, N; Paudel, A; Hamamoto, H

    2012-08-01

    Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

  18. Modelling Farm Animal Welfare

    Directory of Open Access Journals (Sweden)

    Chérie E. Part

    2013-05-01

    Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

  19. Effects of Caffeine and Warrior Stress on Behavioral : An Animal Model

    Science.gov (United States)

    2016-03-14

    typically in the form of food (e.g., chocolate ) and drinks (e.g., coffee, tea, energy drinks, and soft drinks), improves attention and performance...administration in an animal model of neuroleptic therapy . Journal of neuroscience methods 146:159-64 81. Schmidt MV, Muller MB. 2006. Animal models of anxiety

  20. The Supply Chain's Role in Improving Animal Welfare.

    Science.gov (United States)

    Harvey, David; Hubbard, Carmen

    2013-08-14

    Supply chains are already incorporating citizen/consumer demands for improved animal welfare, especially through product differentiation and the associated segmentation of markets. Nonetheless, the ability of the chain to deliver high(er) levels and standards of animal welfare is subject to two critical conditions: (a) the innovative and adaptive capacity of the chain to respond to society's demands; (b) the extent to which consumers actually purchase animal-friendly products. Despite a substantial literature reporting estimates of willingness to pay (WTP) for animal welfare, there is a belief that in practice people vote for substantially more and better animal welfare as citizens than they are willing to pay for as consumers. This citizen-consumer gap has significant consequences on the supply chain, although there is limited literature on the capacity and willingness of supply chains to deliver what the consumer wants and is willing to pay for. This paper outlines an economic analysis of supply chain delivery of improved standards for farm animal welfare in the EU and illustrates the possible consequences of improving animal welfare standards for the supply chain using a prototype belief network analysis.

  1. Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.

    Science.gov (United States)

    Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan

    2016-12-01

    Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome

    DEFF Research Database (Denmark)

    Sangild, Per Torp; Ney, Denise M; Sigalet, David L

    2014-01-01

    enterocolitis, atresia, gastroschisis, volvulus and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, nutritional interventions and growth factor therapies. Animal studies may......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....

  3. Animal models in plastic and reconstructive surgery simulation-a review.

    Science.gov (United States)

    Loh, Charles Yuen Yung; Wang, Aline Yen Ling; Tiong, Vincent Tze Yang; Athanassopoulos, Thanassi; Loh, Meiling; Lim, Philip; Kao, Huang-Kai

    2018-01-01

    The use of live and cadaveric animal models in surgical training is well established as a means of teaching and improving surgical skill in a controlled setting. We aim to review, evaluate, and summarize the models published in the literature that are applicable to Plastic Surgery training. A PubMed search for keywords relating to animal models in Plastic Surgery and the associated procedures was conducted. Animal models that had cross over between specialties such as microsurgery with Neurosurgery and pinnaplasty with ear, nose, and throat surgery were included as they were deemed to be relevant to our training curriculum. A level of evidence and recommendation assessment was then given to each surgical model. Our review found animal models applicable to plastic surgery training in four major categories namely-microsurgery training, flap raising, facial surgery, and hand surgery. Twenty-four separate articles described various methods of practicing microsurgical techniques on different types of animals. Fourteen different articles each described various methods of conducting flap-based procedures which consisted of either local or perforator flap dissection. Eight articles described different models for practicing hand surgery techniques. Finally, eight articles described animal models that were used for head and neck procedures. A comprehensive summary of animal models related to plastic surgery training has been compiled. Cadaveric animal models provide a readily available introduction to many procedures and ought to be used instead of live models when feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Animal models of tinnitus.

    Science.gov (United States)

    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

    Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

  5. The Supply Chain’s Role in Improving Animal Welfare

    Science.gov (United States)

    Harvey, David; Hubbard, Carmen

    2013-01-01

    Simple Summary The ability of supply chains to deliver high(er) levels and standards of animal welfare is subject to two critical conditions: (a) the innovative and adaptive capacity of actors in the chain to respond to society’s demands; (b) consumers actually buying animal-friendly products. Unless citizens are willing to support suppliers who comply with high(er) standards, their votes for better animal welfare risk exporting poor animal welfare to other countries with less rigorous standards. The logic of market failure in the case of animal welfare points to the superiority of consumer subsidies over producer subsidies to deliver improved animal welfare. Abstract Supply chains are already incorporating citizen/consumer demands for improved animal welfare, especially through product differentiation and the associated segmentation of markets. Nonetheless, the ability of the chain to deliver high(er) levels and standards of animal welfare is subject to two critical conditions: (a) the innovative and adaptive capacity of the chain to respond to society’s demands; (b) the extent to which consumers actually purchase animal-friendly products. Despite a substantial literature reporting estimates of willingness to pay (WTP) for animal welfare, there is a belief that in practice people vote for substantially more and better animal welfare as citizens than they are willing to pay for as consumers. This citizen-consumer gap has significant consequences on the supply chain, although there is limited literature on the capacity and willingness of supply chains to deliver what the consumer wants and is willing to pay for. This paper outlines an economic analysis of supply chain delivery of improved standards for farm animal welfare in the EU and illustrates the possible consequences of improving animal welfare standards for the supply chain using a prototype belief network analysis. PMID:26479533

  6. Animal models of sarcoidosis.

    Science.gov (United States)

    Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

    2017-03-01

    Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

  7. Animal models of Alzheimer disease: historical pitfalls and a path forward.

    Science.gov (United States)

    Cavanaugh, Sarah E; Pippin, John J; Barnard, Neal D

    2014-01-01

    Alzheimer disease (AD) is a medically and financially overwhelming condition, and incidence rates are expected to triple by 2050.Despite decades of research in animal models of AD, the disease remains incompletely understood, with few treatment options. This review summarizes historical and current AD research efforts, with emphasis on the disparity between preclinical animal studies and the reality of human disease and how this has impacted clinical trials. Ultimately, we provide a mechanism for shifting the focus of AD research away from animal models to focus primarily on human biology as a means to improve the applicability of research findings to human disease. Implementation of these alternatives may hasten development of improved strategies to prevent, detect, ameliorate, and possibly cure this devastating disease.

  8. Animal Models for Dysphagia Studies: What Have We Learnt So Far.

    Science.gov (United States)

    German, Rebecca Z; Crompton, A W; Gould, Francois D H; Thexton, Allan J

    2017-02-01

    Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes.

  9. Animal Models in Burn Research

    Science.gov (United States)

    Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

    2014-01-01

    Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

  10. The Supply Chain’s Role in Improving Animal Welfare

    Directory of Open Access Journals (Sweden)

    David Harvey

    2013-08-01

    Full Text Available Supply chains are already incorporating citizen/consumer demands for improved animal welfare, especially through product differentiation and the associated segmentation of markets. Nonetheless, the ability of the chain to deliver high(er levels and standards of animal welfare is subject to two critical conditions: (a the innovative and adaptive capacity of the chain to respond to society’s demands; (b the extent to which consumers actually purchase animal-friendly products. Despite a substantial literature reporting estimates of willingness to pay (WTP for animal welfare, there is a belief that in practice people vote for substantially more and better animal welfare as citizens than they are willing to pay for as consumers. This citizen-consumer gap has significant consequences on the supply chain, although there is limited literature on the capacity and willingness of supply chains to deliver what the consumer wants and is willing to pay for. This paper outlines an economic analysis of supply chain delivery of improved standards for farm animal welfare in the EU and illustrates the possible consequences of improving animal welfare standards for the supply chain using a prototype belief network analysis.

  11. Animal-Assisted Therapy for Improving Human Health

    Directory of Open Access Journals (Sweden)

    Sibel Cevizci

    2009-06-01

    Full Text Available ABSTRACT Animal Assisted Therapy (AAT or Pet Therapy is an adjunctive therapy by taking advantage of human and animal interaction, activate the physiological and psychological mechanisms, initiate positive changes improving health in metabolism. In recent years, this interaction are in use to treat psychological and psychiatric disorders such as stress, depression, loneliness, pervasive developmental disorders affect negatively to human health. Furthermore, AAT has been increasingly used to improve quality of life, hypertension, cardiovascular diseases, chronic illnesses such as cancer and AIDS. The aim of this paper is to identify AAT by reviewing human and animal interaction, evaluate how AAT has a scientific background from past to now. Also, we aim to give some information about the risks, institutional applications, some factors referring AAT’s mechanism of action and chronic diseases, psychological and physical improvements provided with animal assisted therapies. The therapy results will be evaluated more advisable providing AAT is being applied with public health specialist, veterinarian, physician, psychologist, psychiatrist and veterinary public health experts who are monitor applications. Especially, the psychosomatic effects result from physical, emotional and play mechanism of action of HDT can be used for improving quality of life in individuals with chronic diseases. In Turkey, there is no any investigation which have been performed in this scientific field. It is quitely important to evaluate the benefits of this therapy accurately and to select various methods proper to diseases. Consequently, it is obvious that AAT will be considered by the healthcare services as a supportive therapy process for improving human health in Turkey and needs further studies. [TAF Prev Med Bull 2009; 8(3.000: 263-272

  12. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  13. Animal Models for Dysphagia Studies: What have we learnt so far

    Science.gov (United States)

    German, Rebecca Z.; Crompton, A.W.; Gould, Francois D. H.; Thexton, Allan J.

    2017-01-01

    Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes. PMID:28132098

  14. Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.

    Science.gov (United States)

    Deslauriers, Jessica; Toth, Mate; Der-Avakian, Andre; Risbrough, Victoria B

    2018-05-15

    Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with ≥20 symptoms. Clinical research increasingly utilizes objective biological measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or physiological responses to complement verbally reported symptoms. This shift toward more-objectively measurable phenotypes enables refinement of current animal models of PTSD, and it supports the incorporation of homologous measures across species. We reviewed >600 articles to examine the ability of current rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances, hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor hypersensitivity) in addition to behavioral phenotypes. Most models reliably produced enduring generalized anxiety-like or depression-like behaviors, as well as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and response to long-term selective serotonin reuptake inhibitors. Although a few paradigms probed fear conditioning/extinction or utilized peripheral immune, sleep, and noninvasive imaging measures, we argue that these should be incorporated more to enhance translation. Data on female subjects, on subjects at different ages across the life span, or on temporal trajectories of phenotypes after stress that can inform model validity and treatment study design are needed. Overall, preclinical (and clinical) PTSD researchers are increasingly incorporating homologous biological measures to assess markers of risk, response, and treatment outcome. This shift is exciting, as we and many others hope it not only will support translation of drug efficacy from animal models to clinical trials but also will potentially improve predictability of stage II for stage III clinical trials. Published by Elsevier Inc.

  15. Overview of Animal Models of Obesity

    Science.gov (United States)

    Lutz, Thomas A.; Woods, Stephen C.

    2012-01-01

    This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

  16. Reproducibility of preclinical animal research improves with heterogeneity of study samples

    Science.gov (United States)

    Vogt, Lucile; Sena, Emily S.; Würbel, Hanno

    2018-01-01

    Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research. PMID:29470495

  17. Animated-simulation modeling facilitates clinical-process costing.

    Science.gov (United States)

    Zelman, W N; Glick, N D; Blackmore, C C

    2001-09-01

    Traditionally, the finance department has assumed responsibility for assessing process costs in healthcare organizations. To enhance process-improvement efforts, however, many healthcare providers need to include clinical staff in process cost analysis. Although clinical staff often use electronic spreadsheets to model the cost of specific processes, PC-based animated-simulation tools offer two major advantages over spreadsheets: they allow clinicians to interact more easily with the costing model so that it more closely represents the process being modeled, and they represent cost output as a cost range rather than as a single cost estimate, thereby providing more useful information for decision making.

  18. Small and large animal models in cardiac contraction research: advantages and disadvantages.

    Science.gov (United States)

    Milani-Nejad, Nima; Janssen, Paul M L

    2014-03-01

    The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart's activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients' lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences. © 2013.

  19. Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model.

    Science.gov (United States)

    Sahin, Ceren; Doostdar, Nazanin; Neill, Joanna C

    2016-10-01

    Negative symptoms in schizophrenia remain an unmet clinical need. There is no licensed treatment specifically for this debilitating aspect of the disorder and effect sizes of new therapies are too small to make an impact on quality of life and function. Negative symptoms are multifactorial but often considered in terms of two domains, expressive deficit incorporating blunted affect and poverty of speech and avolition incorporating asociality and lack of drive. There is a clear need for improved understanding of the neurobiology of negative symptoms which can be enabled through the use of carefully validated animal models. While there are several tests for assessing sociability in animals, tests for blunted affect in schizophrenia are currently lacking. Two paradigms have recently been developed for assessing negative affect of relevance to depression in rats. Here we assess their utility for studying negative symptoms in schizophrenia using our well validated model for schizophrenia of sub-chronic (sc) treatment with Phencyclidine (PCP) in adult female rats. Results demonstrate that sc PCP treatment produces a significant negative affect bias in response to a high value reward in the optimistic and affective bias tests. Our results are not easily explained by the known cognitive deficits induced by sc PCP and support the hypothesis of a negative affective bias in this model. We suggest that further refinement of these two tests will provide a means to investigate the neurobiological basis of negative affect in schizophrenia, thus supporting the assessment of efficacy of new targets for this currently untreated symptom domain. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Animal Models for Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Helieh S. Oz

    2011-01-01

    Full Text Available Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

  1. Animal Models for Periodontal Disease

    Science.gov (United States)

    Oz, Helieh S.; Puleo, David A.

    2011-01-01

    Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

  2. Surface Simplification of 3D Animation Models Using Robust Homogeneous Coordinate Transformation

    Directory of Open Access Journals (Sweden)

    Juin-Ling Tseng

    2014-01-01

    Full Text Available The goal of 3D surface simplification is to reduce the storage cost of 3D models. A 3D animation model typically consists of several 3D models. Therefore, to ensure that animation models are realistic, numerous triangles are often required. However, animation models that have a high storage cost have a substantial computational cost. Hence, surface simplification methods are adopted to reduce the number of triangles and computational cost of 3D models. Quadric error metrics (QEM has recently been identified as one of the most effective methods for simplifying static models. To simplify animation models by using QEM, Mohr and Gleicher summed the QEM of all frames. However, homogeneous coordinate problems cannot be considered completely by using QEM. To resolve this problem, this paper proposes a robust homogeneous coordinate transformation that improves the animation simplification method proposed by Mohr and Gleicher. In this study, the root mean square errors of the proposed method were compared with those of the method proposed by Mohr and Gleicher, and the experimental results indicated that the proposed approach can preserve more contour features than Mohr’s method can at the same simplification ratio.

  3. Animal models.

    Science.gov (United States)

    Walker, Ellen A

    2010-01-01

    As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

  4. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

    Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

  5. Animal models and therapeutic molecular targets of cancer: utility and limitations

    Directory of Open Access Journals (Sweden)

    Cekanova M

    2014-10-01

    Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

  6. An animal model for tinnitus.

    Science.gov (United States)

    Jastreboff, P J; Brennan, J F; Sasaki, C T

    1988-03-01

    Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

  7. Sleep and Obesity: A focus on animal models

    Science.gov (United States)

    Mavanji, Vijayakumar; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.

    2012-01-01

    The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007; Dixon et al., 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity. PMID:22266350

  8. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

    Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

    1998-01-01

    As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

  9. Modelling animal waste pathogen transport from agricultural land to streams

    International Nuclear Information System (INIS)

    Pandey, Pramod K; Soupir, Michelle L; Ikenberry, Charles

    2014-01-01

    The transport of animal waste pathogens from crop land to streams can potentially elevate pathogen levels in stream water. Applying animal manure into crop land as fertilizers is a common practice in developing as well as in developed countries. Manure application into the crop land, however, can cause potential human health. To control pathogen levels in ambient water bodies such as streams, improving our understanding of pathogen transport at farm scale as well as at watershed scale is required. To understand the impacts of crop land receiving animal waste as fertilizers on stream's pathogen levels, here we investigate pathogen indicator transport at watershed scale. We exploited watershed scale hydrological model to estimate the transport of pathogens from the crop land to streams. Pathogen indicator levels (i.e., E. coli levels) in the stream water were predicted. With certain assumptions, model results are reasonable. This study can be used as guidelines for developing the models for calculating the impacts of crop land's animal manure on stream water

  10. Are animal models predictive for human postmortem muscle protein degradation?

    Science.gov (United States)

    Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

    2017-11-01

    A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

  11. Animal models for rotator cuff repair.

    Science.gov (United States)

    Lebaschi, Amir; Deng, Xiang-Hua; Zong, Jianchun; Cong, Guang-Ting; Carballo, Camila B; Album, Zoe M; Camp, Christopher; Rodeo, Scott A

    2016-11-01

    Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. © 2016 New York Academy of Sciences.

  12. Invited review: Experimental design, data reporting, and sharing in support of animal systems modeling research.

    Science.gov (United States)

    McNamara, J P; Hanigan, M D; White, R R

    2016-12-01

    The National Animal Nutrition Program "National Research Support Project 9" supports efforts in livestock nutrition, including the National Research Council's committees on the nutrient requirements of animals. Our objective was to review the status of experimentation and data reporting in animal nutrition literature and to provide suggestions for the advancement of animal nutrition research and the ongoing improvement of field-applied nutrient requirement models. Improved data reporting consistency and completeness represent a substantial opportunity to improve nutrition-related mathematical models. We reviewed a body of nutrition research; recorded common phrases used to describe diets, animals, housing, and environmental conditions; and proposed equivalent numerical data that could be reported. With the increasing availability of online supplementary material sections in journals, we developed a comprehensive checklist of data that should be included in publications. To continue to improve our research effectiveness, studies utilizing multiple research methodologies to address complex systems and measure multiple variables will be necessary. From the current body of animal nutrition literature, we identified a series of opportunities to integrate research focuses (nutrition, reproduction and genetics) to advance the development of nutrient requirement models. From our survey of current experimentation and data reporting in animal nutrition, we identified 4 key opportunities to advance animal nutrition knowledge: (1) coordinated experiments should be designed to employ multiple research methodologies; (2) systems-oriented research approaches should be encouraged and supported; (3) publication guidelines should be updated to encourage and support sharing of more complete data sets; and (4) new experiments should be more rapidly integrated into our knowledge bases, research programs and practical applications. Copyright © 2016 American Dairy Science Association

  13. Animal models of osteogenesis imperfecta: applications in clinical research

    Directory of Open Access Journals (Sweden)

    Enderli TA

    2016-09-01

    Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish

  14. Study of the pathogenesis and treatment of diabetes mellitus through animal models.

    Science.gov (United States)

    Brito-Casillas, Yeray; Melián, Carlos; Wägner, Ana María

    2016-01-01

    Most research in diabetes mellitus (DM) has been conducted in animals, and their replacement is currently a chimera. As compared to when they started to be used by modern science in the 17th century, a very high number of animal models of diabetes is now available, and they provide new insights into almost every aspect of diabetes. Approaches combining human, in vitro, and animal studies are probably the best strategy to improve our understanding of the underlying mechanisms of diabetes, and the choice of the best model to achieve such objective is crucial. Traditionally classified based on pathogenesis as spontaneous or induced models, each has its own advantages and disadvantages. The most common animal models of diabetes are described, and in addition to non-obese diabetic mice, biobreeding diabetes-prone (BB-DP) rats, streptozotocin-induced models, or high-fat diet-induced diabetic C57Bl/6J mice, new valuable models, such as dogs and cats with spontaneous diabetes, are described. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Simple models for studying complex spatiotemporal patterns of animal behavior

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

    Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.

  16. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

  17. Animal Models of Hemophilia

    Science.gov (United States)

    Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

    2013-01-01

    The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

  18. Animal models of exercise and obesity.

    Science.gov (United States)

    Kasper, Christine E

    2013-01-01

    Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

  19. Animal models: an important tool in mycology.

    Science.gov (United States)

    Capilla, Javier; Clemons, Karl V; Stevens, David A

    2007-12-01

    Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

  20. Improving animal health for poverty alleviation and sustainable livelihoods.

    Science.gov (United States)

    Stringer, Andy

    2014-11-29

    Animals are vital to ensuring food security for individuals, families and communities in countries around the world. In this, the latest article in Veterinary Record's series promoting One Health, Andy Stringer, director of veterinary programmes at the Society for the Protection of Animals Abroad, discusses how improving animal health, particularly of poultry and working equids, has the potential to reduce poverty and promote food security and sustainable livelihoods in low-income countries. British Veterinary Association.

  1. Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

    Science.gov (United States)

    Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in

  2. Animal models of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Sagvolden Terje

    2005-07-01

    Full Text Available Abstract Although animals cannot be used to study complex human behaviour such as language, they do have similar basic functions. In fact, human disorders that have animal models are better understood than disorders that do not. ADHD is a heterogeneous disorder. The relatively simple nervous systems of rodent models have enabled identification of neurobiological changes that underlie certain aspects of ADHD behaviour. Several animal models of ADHD suggest that the dopaminergic system is functionally impaired. Some animal models have decreased extracellular dopamine concentrations and upregulated postsynaptic dopamine D1 receptors (DRD1 while others have increased extracellular dopamine concentrations. In the latter case, dopamine pathways are suggested to be hyperactive. However, stimulus-evoked release of dopamine is often decreased in these models, which is consistent with impaired dopamine transmission. It is possible that the behavioural characteristics of ADHD result from impaired dopamine modulation of neurotransmission in cortico-striato-thalamo-cortical circuits. There is considerable evidence to suggest that the noradrenergic system is poorly controlled by hypofunctional α2-autoreceptors in some models, giving rise to inappropriately increased release of norepinephrine. Aspects of ADHD behaviour may result from an imbalance between increased noradrenergic and decreased dopaminergic regulation of neural circuits that involve the prefrontal cortex. Animal models of ADHD also suggest that neural circuits may be altered in the brains of children with ADHD. It is therefore of particular importance to study animal models of the disorder and not normal animals. Evidence obtained from animal models suggests that psychostimulants may not be acting on the dopamine transporter to produce the expected increase in extracellular dopamine concentration in ADHD. There is evidence to suggest that psychostimulants may decrease motor activity by

  3. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

    Science.gov (United States)

    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

  4. Implementation of ICARE learning model using visualization animation on biotechnology course

    Science.gov (United States)

    Hidayat, Habibi

    2017-12-01

    ICARE is a learning model that directly ensure the students to actively participate in the learning process using animation media visualization. ICARE have five key elements of learning experience from children and adult that is introduction, connection, application, reflection and extension. The use of Icare system to ensure that participants have opportunity to apply what have been they learned. So that, the message delivered by lecture to students can be understood and recorded by students in a long time. Learning model that was deemed capable of improving learning outcomes and interest to learn in following learning process Biotechnology with applying the ICARE learning model using visualization animation. This learning model have been giving motivation to participate in the learning process and learning outcomes obtained becomes more increased than before. From the results of student learning in subjects Biotechnology by applying the ICARE learning model using Visualization Animation can improving study results of student from the average value of middle test amounted to 70.98 with the percentage of 75% increased value of final test to be 71.57 with the percentage of 68.63%. The interest to learn from students more increasing visits of student activities at each cycle, namely the first cycle obtained average value by 33.5 with enough category. The second cycle is obtained an average value of 36.5 to good category and third cycle the average value of 36.5 with a student activity to good category.

  5. SketchBio: a scientist's 3D interface for molecular modeling and animation.

    Science.gov (United States)

    Waldon, Shawn M; Thompson, Peter M; Hahn, Patrick J; Taylor, Russell M

    2014-10-30

    Because of the difficulties involved in learning and using 3D modeling and rendering software, many scientists hire programmers or animators to create models and animations. This both slows the discovery process and provides opportunities for miscommunication. Working with multiple collaborators, a tool was developed (based on a set of design goals) to enable them to directly construct models and animations. SketchBio is presented, a tool that incorporates state-of-the-art bimanual interaction and drop shadows to enable rapid construction of molecular structures and animations. It includes three novel features: crystal-by-example, pose-mode physics, and spring-based layout that accelerate operations common in the formation of molecular models. Design decisions and their consequences are presented, including cases where iterative design was required to produce effective approaches. The design decisions, novel features, and inclusion of state-of-the-art techniques enabled SketchBio to meet all of its design goals. These features and decisions can be incorporated into existing and new tools to improve their effectiveness.

  6. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

    Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.

    2014-01-01

    makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However...

  8. Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

    Directory of Open Access Journals (Sweden)

    Schneider Erich

    2007-08-01

    Full Text Available Abstract Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation in concert with the AO Research Institute (ARI, and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1 Intelligent study designs to receive appropriate answers; 2 Minimal complication rates (5 to max. 10%; 3 Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA audit of protocols in GLP studies; 4 Sufficient details for materials and methods applied; 5 Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences; 6 Post-operative management with emphasis on analgesia and follow-up examinations; 7 Study protocols to satisfy criteria established for a "justified animal study"; 8 Surgical expertise to conduct surgery on animals; 9 Pilot studies as a critical part of model validation and powering of the definitive study design

  9. Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.

    Science.gov (United States)

    Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

    2016-01-01

    Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

  10. Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

    Directory of Open Access Journals (Sweden)

    Mohan Kumar Pasupuleti

    2016-01-01

    Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

  11. Small Animal Models for Evaluating Filovirus Countermeasures.

    Science.gov (United States)

    Banadyga, Logan; Wong, Gary; Qiu, Xiangguo

    2018-05-11

    The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (such as mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model. In the past several years, however, the filovirus field has witnessed the continued refinement of the mouse and guinea pig models of disease, as well as the introduction of the hamster and ferret models. We now have small animal models for most human-pathogenic filoviruses, many of which are susceptible to wild type virus and demonstrate key features of disease, including robust virus replication, coagulopathy, and immune system dysfunction. Although none of these small animal model systems perfectly recapitulates Ebola virus disease or Marburg virus disease on its own, collectively they offer a nearly complete set of tools in which to carry out the preclinical development of novel antiviral drugs.

  12. Social defeat models in animal science: What we have learned from rodent models.

    Science.gov (United States)

    Toyoda, Atsushi

    2017-07-01

    Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

  13. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-11-01

    Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  14. Osteoarthritis: new insights in animal models.

    Science.gov (United States)

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

  15. Animal models of osteoporosis - necessity and limitations

    Directory of Open Access Journals (Sweden)

    Turner A. Simon

    2001-06-01

    Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

  16. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

    Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

  17. Mid-term financial impact of animal welfare improvements in Dutch broiler production.

    Science.gov (United States)

    Gocsik, E; Lansink, A G J M Oude; Saatkamp, H W

    2013-12-01

    This study used a stochastic bioeconomic simulation model to simulate the business and financial risk of different broiler production systems over a 5-yr period. Simulation analysis was conducted using the @Risk add-in in MS Excel. To compare the impact of different production systems on economic feasibility, 2 cases were considered. The first case focused on the economic feasibility of a completely new system, whereas the second examined economic feasibilities when a farm switches from a conventional to an animal welfare-improving production system. A sensitivity analysis was conducted to assess the key drivers of economic feasibility and to reveal systematic differences across production systems. The study shows that economic feasibility of systems with improved animal welfare predominantly depends on the price that farmers receive. Moreover, the study demonstrates the importance of the level and variation of the price premium for improved welfare, particularly in the first 5 yr after conversion. The economic feasibility of the production system increases with the level of welfare improvements for a sufficiently high price level for broiler meat and low volatility in producer prices. If this is not the case, however, risk attitudes of farmers become important as well as the use of potential risk management instruments.

  18. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

    Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

    2017-07-01

    Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

  19. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Leffa, Douglas Teixeira; de Souza, Andressa; Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Grevet, Eugenio Horacio; Caumo, Wolnei; de Souza, Diogo Onofre; Rohde, Luis Augusto Paim; Torres, Iraci L S

    2016-02-01

    Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals. Copyright © 2016. Published by Elsevier B.V.

  1. Latest animal models for anti-HIV drug discovery.

    Science.gov (United States)

    Sliva, Katja

    2015-02-01

    HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

  2. Animal models for auditory streaming

    Science.gov (United States)

    Itatani, Naoya

    2017-01-01

    Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

  3. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  4. Sustainable Improvement of Animal Production and Health

    International Nuclear Information System (INIS)

    Odongo, N.E.; Garcia, M.; Viljoen, G.J.

    2010-01-01

    The world's poorest people, some one billion living mostly in Africa and Asia, depend on livestock for their day-to-day livelihood. To reduce poverty, fight hunger and ensure global food security, there is an urgent need to increase livestock production in sustainable ways. However, livestock production in developing countries is constrained by low genetic potential of the animals, poor nutrition and husbandry practices and infectious diseases. Nuclear techniques, when applied in conjunction with conventional methods, can identify constraints to livestock productivity as well as interventions that lead to their reduction or elimination in ways that are economically and socially acceptable. The challenge is how best to exploit these techniques for solving problems faced by livestock keepers within the many agricultural production systems that exist in developing countries and demonstrating their advantages to owners, local communities and government authorities. This publication is a compilation of the contributions emanating from an international Symposium on Sustainable Improvement of Animal Production and Health organised by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture in cooperation with the Animal Production and Health Division of FAO. It provides invaluable information not only on how nuclear and related techniques can be used to support sustainable livestock production systems, but also about the constraints and opportunities for using these techniques in developing countries; it also attempts to identify specific research needs and gaps and new options for using these techniques for solving established and emerging problems. As such, it is hoped that the information presented and suggestions made will provide valuable guidance to scientists in both the public and private sectors as well as to government and institutional policy and decision makers. The Symposium comprised a plenary session and four thematic sessions, covering (i

  5. Sustainable Improvement of Animal Production and Health

    Energy Technology Data Exchange (ETDEWEB)

    Odongo, N E; Garcia, M; Viljoen, G J [Animal Production and Health Subprogramme, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, International Atomic Agency, Vienna (Austria)

    2010-07-01

    The world's poorest people, some one billion living mostly in Africa and Asia, depend on livestock for their day-to-day livelihood. To reduce poverty, fight hunger and ensure global food security, there is an urgent need to increase livestock production in sustainable ways. However, livestock production in developing countries is constrained by low genetic potential of the animals, poor nutrition and husbandry practices and infectious diseases. Nuclear techniques, when applied in conjunction with conventional methods, can identify constraints to livestock productivity as well as interventions that lead to their reduction or elimination in ways that are economically and socially acceptable. The challenge is how best to exploit these techniques for solving problems faced by livestock keepers within the many agricultural production systems that exist in developing countries and demonstrating their advantages to owners, local communities and government authorities. This publication is a compilation of the contributions emanating from an international Symposium on Sustainable Improvement of Animal Production and Health organised by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture in cooperation with the Animal Production and Health Division of FAO. It provides invaluable information not only on how nuclear and related techniques can be used to support sustainable livestock production systems, but also about the constraints and opportunities for using these techniques in developing countries; it also attempts to identify specific research needs and gaps and new options for using these techniques for solving established and emerging problems. As such, it is hoped that the information presented and suggestions made will provide valuable guidance to scientists in both the public and private sectors as well as to government and institutional policy and decision makers. The Symposium comprised a plenary session and four thematic sessions, covering (i

  6. Animal models of preeclampsia; uses and limitations.

    LENUS (Irish Health Repository)

    McCarthy, F P

    2012-01-31

    Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

  7. Comparative systems biology between human and animal models based on next-generation sequencing methods.

    Science.gov (United States)

    Zhao, Yu-Qi; Li, Gong-Hua; Huang, Jing-Fei

    2013-04-01

    Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

  8. Using Computational and Mechanical Models to Study Animal Locomotion

    Science.gov (United States)

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas

    2012-01-01

    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: “Integrating living and physical systems.” PMID:22988026

  9. Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

    Science.gov (United States)

    Chujitarom, Wannaporn; Piriyasurawong, Pallop

    2017-01-01

    This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

  10. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  11. Animal models of cerebral arterial gas embolism

    NARCIS (Netherlands)

    Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

    2012-01-01

    Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties

  12. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

    The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

  13. Advances in Animal Models of Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhang Hang

    2015-12-01

    Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.

  14. Immunological considerations of modern animal models of malignant primary brain tumors

    Directory of Open Access Journals (Sweden)

    James C David

    2009-10-01

    Full Text Available Abstract Recent advances in animal models of glioma have facilitated a better understanding of biological mechanisms underlying gliomagenesis and glioma progression. The limitations of existing therapy, including surgery, chemotherapy, and radiotherapy, have prompted numerous investigators to search for new therapeutic approaches to improve quantity and quality of survival from these aggressive lesions. One of these approaches involves triggering a tumor specific immune response. However, a difficulty in this approach is the the scarcity of animal models of primary CNS neoplasms which faithfully recapitulate these tumors and their interaction with the host's immune system. In this article, we review the existing methods utilized to date for modeling gliomas in rodents, with a focus on the known as well as potential immunological aspects of these models. As this review demonstrates, many of these models have inherent immune system limitations, and the impact of these limitations on studies on the influence of pre-clinical therapeutics testing warrants further attention.

  15. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. A partial hearing animal model for chronic electro-acoustic stimulation

    Science.gov (United States)

    Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

    2014-08-01

    Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual

  17. Elements of episodic-like memory in animal models.

    Science.gov (United States)

    Crystal, Jonathon D

    2009-03-01

    Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

  18. Testing flow diversion in animal models: a systematic review.

    Science.gov (United States)

    Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E

    2016-04-01

    Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

  19. Chimeric animal models in human stem cell biology.

    Science.gov (United States)

    Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

    2009-01-01

    The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

  20. Training for laparoscopic Nissen fundoplication with a newly designed model: a replacement for animal tissue models?

    Science.gov (United States)

    Christie, Lorna; Goossens, Richard; Jakimowicz, Jack J.

    2010-01-01

    Background To bridge the early learning curve for laparoscopic Nissen fundoplication from the clinical setting to a safe environment, training models can be used. This study aimed to develop a reusable, low-cost model to be used for training in laparoscopic Nissen fundoplication procedure as an alternative to the use of animal tissue models. Methods From artificial organs and tissue, an anatomic model of the human upper abdomen was developed for training in performing laparoscopic Nissen fundoplication. The 20 participants and tutors in the European Association for Endoscopic Surgery (EAES) upper gastrointestinal surgery course completed four complementary tasks of laparoscopic Nissen fundoplication with the artificial model, then compared the realism, haptic feedback, and training properties of the model with those of animal tissue models. Results The main difference between the two training models was seen in the properties of the stomach. The wrapping of the stomach in the artificial model was rated significantly lower than that in the animal tissue model (mean, 3.6 vs. 4.2; p = 0.010). The main criticism of the stomach of the artificial model was that it was too rigid for making a proper wrap. The suturing of the stomach wall, however, was regarded as fairly realistic (mean, 3.6). The crura on the artificial model were rated better (mean, 4.3) than those on the animal tissue (mean, 4.0), although the difference was not significant. The participants regarded the model as a good to excellent (mean, 4.3) training tool. Conclusion The newly developed model is regarded as a good tool for training in laparoscopic Nissen fundoplication procedure. It is cheaper, more durable, and more readily available for training and can therefore be used in every training center. The stomach of this model, however, still needs improvement because it is too rigid for making the wrap. PMID:20526629

  1. Animal models in biological and biomedical research - experimental and ethical concerns.

    Science.gov (United States)

    Andersen, Monica L; Winter, Lucile M F

    2017-09-04

    Animal models have been used in experimental research to increase human knowledge and contribute to finding solutions to biological and biomedical questions. However, increased concern for the welfare of the animals used, and a growing awareness of the concept of animal rights, has brought a greater focus on the related ethical issues. In this review, we intend to give examples on how animals are used in the health research related to some major health problems in Brazil, as well as to stimulate discussion about the application of ethics in the use of animals in research and education, highlighting the role of National Council for the Control of Animal Experimentation (Conselho Nacional de Controle de Experimentação Animal - CONCEA) in these areas. In 2008, Brazil emerged into a new era of animal research regulation, with the promulgation of Law 11794, previously known as the Arouca Law, resulting in an increased focus, and rapid learning experience, on questions related to all aspects of animal experimentation. The law reinforces the idea that animal experiments must be based on ethical considerations and integrity-based assumptions, and provides a regulatory framework to achieve this. This review describes the health research involving animals and the current Brazilian framework for regulating laboratory animal science, and hopes to help to improve the awareness of the scientific community of these ethical and legal rules.

  2. Using animation quality metric to improve efficiency of global illumination computation for dynamic environments

    Science.gov (United States)

    Myszkowski, Karol; Tawara, Takehiro; Seidel, Hans-Peter

    2002-06-01

    In this paper, we consider applications of perception-based video quality metrics to improve the performance of global lighting computations for dynamic environments. For this purpose we extend the Visible Difference Predictor (VDP) developed by Daly to handle computer animations. We incorporate into the VDP the spatio-velocity CSF model developed by Kelly. The CSF model requires data on the velocity of moving patterns across the image plane. We use the 3D image warping technique to compensate for the camera motion, and we conservatively assume that the motion of animated objects (usually strong attractors of the visual attention) is fully compensated by the smooth pursuit eye motion. Our global illumination solution is based on stochastic photon tracing and takes advantage of temporal coherence of lighting distribution, by processing photons both in the spatial and temporal domains. The VDP is used to keep noise inherent in stochastic methods below the sensitivity level of the human observer. As a result a perceptually-consistent quality across all animation frames is obtained.

  3. Animal models of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Snehlata V Gajbhiye

    2015-01-01

    Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

  4. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease

    Science.gov (United States)

    Graham, Melanie L.; Prescott, Mark J.

    2015-01-01

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812

  5. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    Tamar Farfel-Becker

    2011-11-01

    Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

  6. Animal models for Gaucher disease research.

    Science.gov (United States)

    Farfel-Becker, Tamar; Vitner, Einat B; Futerman, Anthony H

    2011-11-01

    Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

  7. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals. PMID:26949505

  8. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Masoud Soheili

    2015-11-01

    Full Text Available Objective(s:Neurodegenerative Alzheimer’s disease (AD is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP, an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON and lavender (CE treated rats and two Alzheimeric groups including the vehicle (ALZ and lavender (AE treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion:The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  9. Animal models in genomic research: Techniques, applications, and roles for nurses.

    Science.gov (United States)

    Osier, Nicole D; Pham, Lan; Savarese, Amanda; Sayles, Kendra; Alexander, Sheila A

    2016-11-01

    Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Final model of multicriterionevaluation of animal welfare

    DEFF Research Database (Denmark)

    Bonde, Marianne; Botreau, R; Bracke, MBM

    One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfar......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare...

  11. Retinal Cell Degeneration in Animal Models

    Directory of Open Access Journals (Sweden)

    Masayuki Niwa

    2016-01-01

    Full Text Available The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced, autoimmune (experimental autoimmune encephalomyelitis, mechanical stress (optic nerve crush-induced, light-induced and ischemia (transient retinal ischemia-induced. The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

  12. Animal Models of Hemophilia and Related Bleeding Disorders

    Science.gov (United States)

    Lozier, Jay N.; Nichols, Timothy C.

    2013-01-01

    Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

  13. Henipavirus Infections: Lessons from Animal Models

    Directory of Open Access Journals (Sweden)

    Kévin P. Dhondt

    2013-04-01

    Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

  14. Animal models of asthma: utility and limitations

    Directory of Open Access Journals (Sweden)

    Aun MV

    2017-11-01

    Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

  15. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

    Full Text Available Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

  16. Animal models of yellow fever and their application in clinical research.

    Science.gov (United States)

    Julander, Justin G

    2016-06-01

    Yellow fever virus (YFV) is an arbovirus that causes significant human morbidity and mortality. This virus has been studied intensively over the past century, although there are still no treatment options for those who become infected. Periodic and unpredictable yellow fever (YF) outbreaks in Africa and South America continue to occur and underscore the ongoing need to further understand this viral disease and to develop additional countermeasures to prevent or treat cases of illness. The use of animal models of YF is critical to accomplishing this goal. There are several animal models of YF that replicate various aspects of clinical disease and have provided insight into pathogenic mechanisms of the virus. These typically include mice, hamsters and non-human primates (NHP). The utilities and shortcomings of the available animal models of YF are discussed. Information on recent discoveries that have been made in the field of YFV research is also included as well as important future directions in further ameliorating the morbidity and mortality that occur as a result of YFV infection. It is anticipated that these model systems will help facilitate further improvements in the understanding of this virus and in furthering countermeasures to prevent or treat infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The prototypical ranitidine analog JWS-USC-75-IX improves information processing and cognitive function in animal models.

    Science.gov (United States)

    Terry, Alvin V; Buccafusco, Jerry J; Herman, Elizabeth J; Callahan, Patrick M; Beck, Wayne D; Warner, Samantha; Vandenhuerk, Leah; Bouchard, Kristy; Schwarz, Gary M; Gao, Jie; Chapman, James M

    2011-03-01

    This study was designed to evaluate further a prototypical ranitidine analog, JWS-USC-75-IX, [(3-[[[2-[[(5-dimethylaminomethyl)-2-furanyl]methyl]thio]ethyl]amino]-4-nitropyridazine, JWS], for neuropharmacologic properties that would theoretically be useful for treating cognitive and noncognitive behavioral symptoms of neuropsychiatric disorders. JWS was previously found to inhibit acetylcholinesterase (AChE) activity, serve as a potent ligand at muscarinic M₂ acetylcholine receptors, and elicit positive effects on spatial learning, passive avoidance, and working memory in rodents. In the current study, JWS was evaluated for binding activity at more than 60 neurotransmitter receptors, transporters, and ion channels, as well as for inhibitory activity at AChE and butyrylcholinesterase (BChE). The results indicate that JWS inhibits AChE and BChE at low (micromolar) concentrations and that it is a functional antagonist at M₂ receptors (K(B) = 320 nM). JWS was subsequently evaluated orally across additional behavioral assays in rodents (dose range, 0.03-10.0 mg/kg) as well as nonhuman primates (dose range, 0.05-2.0 mg/kg). In rats, JWS improved prepulse inhibition (PPI) of the acoustic startle response in nonimpaired rats and attenuated PPI deficits in three pharmacologic impairment models. JWS also attenuated scopolamine and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801)-related impairments in a spontaneous novel object recognition task and a five-choice serial reaction time task, respectively. In monkeys, JWS elicited dose-dependent improvements of a delayed match-to-sample task as well as an attention-related version of the task where randomly presented (task-relevant) distractors were presented. Thus, JWS (potentially via effects at several drug targets) improves information processing, attention, and memory in animal models and could potentially treat the cognitive and behavioral symptoms of some neuropsychiatric illnesses.

  18. Modeling individual animal histories with multistate capture–recapture models

    Science.gov (United States)

    Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.

    2009-01-01

    Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide

  19. Advances in genome editing for improved animal breeding: A review

    Directory of Open Access Journals (Sweden)

    Shakil Ahmad Bhat

    2017-11-01

    Full Text Available Since centuries, the traits for production and disease resistance are being targeted while improving the genetic merit of domestic animals, using conventional breeding programs such as inbreeding, outbreeding, or introduction of marker-assisted selection. The arrival of new scientific concepts, such as cloning and genome engineering, has added a new and promising research dimension to the existing animal breeding programs. Development of genome editing technologies such as transcription activator-like effector nuclease, zinc finger nuclease, and clustered regularly interspaced short palindromic repeats systems begun a fresh era of genome editing, through which any change in the genome, including specific DNA sequence or indels, can be made with unprecedented precision and specificity. Furthermore, it offers an opportunity of intensification in the frequency of desirable alleles in an animal population through gene-edited individuals more rapidly than conventional breeding. The specific research is evolving swiftly with a focus on improvement of economically important animal species or their traits all of which form an important subject of this review. It also discusses the hurdles to commercialization of these techniques despite several patent applications owing to the ambiguous legal status of genome-editing methods on account of their disputed classification. Nonetheless, barring ethical concerns gene-editing entailing economically important genes offers a tremendous potential for breeding animals with desirable traits.

  20. Animal model of thermal injuries

    Directory of Open Access Journals (Sweden)

    F. Bečić

    2003-11-01

    Full Text Available Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury.New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo. During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 ± 2°C, and in the air with normal humidity level. All animals took food and water ad libitum.Rabbits received anesthesia - intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm. Burns were caused by contact with a round metal seal, heated at 80°C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2 was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4°C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.

  1. Animal models of drug addiction.

    Science.gov (United States)

    García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

    2017-09-29

    The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

  2. Osteoarthritis: New Insights in Animal Models

    OpenAIRE

    Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

  3. Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

    Science.gov (United States)

    Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

    2017-10-01

    The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

  4. Considerations for the design and execution of protocols for animal research and treatment to improve reproducibility and standardization: "DEPART well-prepared and ARRIVE safely".

    Science.gov (United States)

    Smith, M M; Clarke, E C; Little, C B

    2017-03-01

    To review the factors in experimental design that contribute to poor translation of pre-clinical research to therapies for patients with osteoarthritis (OA) and how this might be improved. Narrative review of the literature, and evaluation of the different stages of design conduct and analysis of studies using animal models of OA to define specific issues that might reduce quality of evidence and how this can be minimised. Preventing bias and improving experimental rigour and reporting are important modifiable factors to improve translation from pre-clinical animal models to successful clinical trials of therapeutic agents. Despite publication and adoption by many journals of guidelines such as Animals in Research: Reporting In Vivo Experiments (ARRIVE), experimental animal studies published in leading rheumatology journals are still deficient in their reporting. In part, this may be caused by researchers first consulting these guidelines after the completion of experiments, at the time of publication. This review discusses factors that can (1) bias the outcome of experimental studies using animal models of osteoarthritis or (2) alter the quality of evidence for translation. We propose a checklist to consult prior to starting experiments; in the Design and Execution of Protocols for Animal Research and Treatment (DEPART). Following DEPART during the design phase will enable completion of the ARRIVE checklist at the time of publication, and thus improve the quality of evidence for inclusion of experimental animal research in meta-analyses and systematic reviews: "DEPART well-prepared and ARRIVE safely". Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Animal Models for Evaluation of Bone Implants and Devices: Comparative Bone Structure and Common Model Uses.

    Science.gov (United States)

    Wancket, L M

    2015-09-01

    Bone implants and devices are a rapidly growing field within biomedical research, and implants have the potential to significantly improve human and animal health. Animal models play a key role in initial product development and are important components of nonclinical data included in applications for regulatory approval. Pathologists are increasingly being asked to evaluate these models at the initial developmental and nonclinical biocompatibility testing stages, and it is important to understand the relative merits and deficiencies of various species when evaluating a new material or device. This article summarizes characteristics of the most commonly used species in studies of bone implant materials, including detailed information about the relevance of a particular model to human bone physiology and pathology. Species reviewed include mice, rats, rabbits, guinea pigs, dogs, sheep, goats, and nonhuman primates. Ultimately, a comprehensive understanding of the benefits and limitations of different model species will aid in rigorously evaluating a novel bone implant material or device. © The Author(s) 2015.

  6. Reviewing model application to support animal health decision making.

    Science.gov (United States)

    Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann

    2011-04-01

    Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Classic and New Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Javier Blesa

    2012-01-01

    Full Text Available Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson’s Disease (PD is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA, 1-methyl-1,2,3,6-tetrahydropiridine (MPTP, rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

  8. Elementary of animal model for percutaneous and ocular penetration

    Directory of Open Access Journals (Sweden)

    Kalpesh Chhotalal Ashara

    2016-12-01

    Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

  9. Computer-animated model of accommodation and presbyopia.

    Science.gov (United States)

    Goldberg, Daniel B

    2015-02-01

    To understand, demonstrate, and further research the mechanisms of accommodation and presbyopia. Private practice, Little Silver, New Jersey, USA. Experimental study. The CAMA 2.0 computer-animated model of accommodation and presbyopia was produced in collaboration with an experienced medical animator using Autodesk Maya animation software and Adobe After Effects. The computer-animated model demonstrates the configuration and synchronous movements of all accommodative elements. A new classification of the zonular apparatus based on structure and function is proposed. There are 3 divisions of zonular fibers; that is, anterior, crossing, and posterior. The crossing zonular fibers form a scaffolding to support the lens; the anterior and posterior zonular fibers work reciprocally to achieve focused vision. The model demonstrates the important support function of Weiger ligament. Dynamic movement of the ora serrata demonstrates that the forces of ciliary muscle contraction store energy for disaccommodation in the elastic choroid. The flow of aqueous and vitreous provides strong evidence for our understanding of the hydrodynamic interactions during the accommodative cycle. The interaction may result from the elastic stretch in the choroid transmitted to the vitreous rather than from vitreous pressue. The model supports the concept that presbyopia results from loss of elasticity and increasing ocular rigidity in both the lenticular and extralenticular structures. The computer-animated model demonstrates the structures of accommodation moving in synchrony and might enhance understanding of the mechanisms of accommodation and presbyopia. Dr. Goldberg is a consultant to Acevision, Inc., and Bausch & Lomb. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  10. A dynamic Brownian bridge movement model to estimate utilization distributions for heterogeneous animal movement.

    Science.gov (United States)

    Kranstauber, Bart; Kays, Roland; Lapoint, Scott D; Wikelski, Martin; Safi, Kamran

    2012-07-01

    1. The recently developed Brownian bridge movement model (BBMM) has advantages over traditional methods because it quantifies the utilization distribution of an animal based on its movement path rather than individual points and accounts for temporal autocorrelation and high data volumes. However, the BBMM assumes unrealistic homogeneous movement behaviour across all data. 2. Accurate quantification of the utilization distribution is important for identifying the way animals use the landscape. 3. We improve the BBMM by allowing for changes in behaviour, using likelihood statistics to determine change points along the animal's movement path. 4. This novel extension, outperforms the current BBMM as indicated by simulations and examples of a territorial mammal and a migratory bird. The unique ability of our model to work with tracks that are not sampled regularly is especially important for GPS tags that have frequent failed fixes or dynamic sampling schedules. Moreover, our model extension provides a useful one-dimensional measure of behavioural change along animal tracks. 5. This new method provides a more accurate utilization distribution that better describes the space use of realistic, behaviourally heterogeneous tracks. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

  11. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

    Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

  12. Stress and adaptation : Toward ecologically relevant animal models

    NARCIS (Netherlands)

    Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke

    Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.

  13. Using smartphones to improve animal health and food security ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-05-05

    May 5, 2016 ... The app is also helping farmers raise healthier animals and improve their own ... and found to be a convenient and user-friendly tool for learning and ... of smartphone-based knowledge mobilization technology for building the ...

  14. Science and animal models of marrow stimulation for cartilage repair.

    Science.gov (United States)

    Fortier, Lisa A; Cole, Brian J; McIlwraith, C Wayne

    2012-03-01

    Microfracture of subchondral bone to enhance cartilage repair is a popular surgical technique used in human and animal patients. Clinical results with resolution or improvement in pain are promising and last on average for 2 to 3 years. Animal studies aimed at understanding microfracture indicate that the repair tissue continues to remodel toward chondrogenesis for at least a year, but longer term results are not available to gain insight into the mechanism of microfracture function or failure over time. Subchondral bone sclerosis and central lesional osteophyte formation following subchondral bone microfracture have been observed in animal models of microfracture, but studies do not provide any insight into the etiology of these pathologies. The continued maturation of microfracture repair tissue over time supports further investigation of microfracture or microfracture-augmented cartilage repair procedures with caution for the investigator and clinician to be observant for conditions that lead to subchondral bone sclerosis or central osteophyte formation, and what affect these boney reactions have on clinical outcome.

  15. Neuroprotective properties of curcumin in toxin-base animal models of Parkinson's disease: a systematic experiment literatures review.

    Science.gov (United States)

    Wang, Xin-Shi; Zhang, Zeng-Rui; Zhang, Man-Man; Sun, Miao-Xuan; Wang, Wen-Wen; Xie, Cheng-Long

    2017-08-17

    Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective actions of curcumin have been documented for experimental therapy in Parkinson's disease (PD). In this study, we used a systematic review to comprehensively assess the efficacy of curcumin in experimental PD. Using electronic and manual search for the literatures, we identified studies describing the efficacy of curcumin in animal models of PD. We identified 13 studies with a total of 298 animals describing the efficacy of curcumin in animal models of PD. The methodological quality of all preclinical trials is ranged from 2 to 5. The majority of the experiment studies demonstrated that curcumin was more significantly neuroprotection effective than control groups for treating PD. Among them, five studies indicated that curcumin had an anti-inflammatory effect in the PD animal models (p curcumin, by which it protected substantia nigra neurons and improved striatal dopamine levels. Furthermore, two studies in this review displayed that curcumin treatment was also effective in reducing neuronal apoptosis and improving functional outcome in animal models of PD. Most of the preclinical studies demonstrated the positive findings while one study reported that curcumin had no beneficial effects against Mn-induced disruption of hippocampal metal and neurotransmitter homeostasis. The results demonstrated a marked efficacy of curcumin in experimental model of PD, suggesting curcumin probably a candidate neuroprotective drug for human PD patients.

  16. Animal Models Used to Explore Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S

    2016-01-01

    OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...

  17. Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

    Science.gov (United States)

    Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

    2018-02-01

    Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

  18. Laboratory animal models for esophageal cancer

    Directory of Open Access Journals (Sweden)

    Dhanya Venugopalan Nair

    2016-11-01

    Full Text Available The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer.

  19. Animal Models of Diabetic Retinopathy: Summary and Comparison

    Science.gov (United States)

    Lo, Amy C. Y.

    2013-01-01

    Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

  20. Improved nonhuman animal welfare is related more to income equality than it is to income.

    Science.gov (United States)

    Morris, Michael C

    2013-01-01

    The link between nonhuman animal welfare, income, and income inequality (Gini coefficient) was tested using consumption of animal products, laws protecting animals on the farm from the worst abuses, and animals used in experimentation as indicators. Experimentation on all animals and on rodents significantly increased in high-income European countries, although there was some evidence that the increase in experimentation on cats and dogs started to flatten out for the highest income countries. Consumption of all flesh products in high-income countries declined in more equal societies. More equal high-income countries also had stricter regulations protecting animals, although the same correlation was not seen between U.S. states. In New Zealand, there was some evidence that testing on cats and dogs declined during years when equality was improving. The results provide little evidence for a Kuznets effect of income on animal welfare, with the possible exception of companion animal treatment. They do, however, suggest that greater equality can be a predictor for better treatment of animals. Previous research has strongly suggested that social conditions for humans improve with greater equality. The same may be true for nonhuman animals. Alternatively, conditions conducive to improving human income equality may also lead to better animal welfare outcomes.

  1. Joint estimation over multiple individuals improves behavioural state inference from animal movement data.

    Science.gov (United States)

    Jonsen, Ian

    2016-02-08

    State-space models provide a powerful way to scale up inference of movement behaviours from individuals to populations when the inference is made across multiple individuals. Here, I show how a joint estimation approach that assumes individuals share identical movement parameters can lead to improved inference of behavioural states associated with different movement processes. I use simulated movement paths with known behavioural states to compare estimation error between nonhierarchical and joint estimation formulations of an otherwise identical state-space model. Behavioural state estimation error was strongly affected by the degree of similarity between movement patterns characterising the behavioural states, with less error when movements were strongly dissimilar between states. The joint estimation model improved behavioural state estimation relative to the nonhierarchical model for simulated data with heavy-tailed Argos location errors. When applied to Argos telemetry datasets from 10 Weddell seals, the nonhierarchical model estimated highly uncertain behavioural state switching probabilities for most individuals whereas the joint estimation model yielded substantially less uncertainty. The joint estimation model better resolved the behavioural state sequences across all seals. Hierarchical or joint estimation models should be the preferred choice for estimating behavioural states from animal movement data, especially when location data are error-prone.

  2. A commentary on domestic animals as dual-purpose models that benefit agricultural and biomedical research.

    Science.gov (United States)

    Ireland, J J; Roberts, R M; Palmer, G H; Bauman, D E; Bazer, F W

    2008-10-01

    Research on domestic animals (cattle, swine, sheep, goats, poultry, horses, and aquatic species) at land grant institutions is integral to improving the global competitiveness of US animal agriculture and to resolving complex animal and human diseases. However, dwindling federal and state budgets, years of stagnant funding from USDA for the Competitive State Research, Education, and Extension Service National Research Initiative (CSREES-NRI) Competitive Grants Program, significant reductions in farm animal species and in numbers at land grant institutions, and declining enrollment for graduate studies in animal science are diminishing the resources necessary to conduct research on domestic species. Consequently, recruitment of scientists who use such models to conduct research relevant to animal agriculture and biomedicine at land grant institutions is in jeopardy. Concerned stakeholders have addressed this critical problem by conducting workshops, holding a series of meetings with USDA and National Institutes of Health (NIH) officials, and developing a white paper to propose solutions to obstacles impeding the use of domestic species as dual-purpose animal models for high-priority problems common to agriculture and biomedicine. In addition to shortfalls in research support and human resources, overwhelming use of mouse models in biomedicine, lack of advocacy from university administrators, long-standing cultural barriers between agriculture and human medicine, inadequate grantsmanship by animal scientists, and a scarcity of key reagents and resources are major roadblocks to progress. Solutions will require a large financial enhancement of USDA's Competitive Grants Program, educational programs geared toward explaining how research using agricultural animals benefits both animal agriculture and human health, and the development of a new mind-set in land grant institutions that fosters greater cooperation among basic and applied researchers. Recruitment of

  3. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

  4. Laser acupuncture improves memory impairment in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Wannanon, Panakaporn; Tong-un, Terdthai

    2013-10-01

    The burden of Alzheimer's disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer's disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180-220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer's disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential. Copyright © 2013. Published by Elsevier B.V.

  5. Large Animal Stroke Models vs. Rodent Stroke Models, Pros and Cons, and Combination?

    Science.gov (United States)

    Cai, Bin; Wang, Ning

    2016-01-01

    Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009.

  6. Fantastic animals as an experimental model to teach animal adaptation

    Directory of Open Access Journals (Sweden)

    Veronesi Paola

    2007-08-01

    Full Text Available Abstract Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy. Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities.

  7. Fantastic animals as an experimental model to teach animal adaptation

    Science.gov (United States)

    Guidetti, Roberto; Baraldi, Laura; Calzolai, Caterina; Pini, Lorenza; Veronesi, Paola; Pederzoli, Aurora

    2007-01-01

    Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy). Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities. PMID:17767729

  8. The complete guide to blender graphics computer modeling and animation

    CERN Document Server

    Blain, John M

    2014-01-01

    Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments

  9. Animal models of GM2 gangliosidosis: utility and limitations

    Science.gov (United States)

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  10. Animal models of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

    2015-03-01

    Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  11. TNFα depleting therapy improves fertility and animal welfare in TNFα-driven transgenic models of polyarthritis when administered in their routine breeding

    Science.gov (United States)

    Naylor, Amy J.; Desanti, Guillaume; Saghir, Atif N.

    2017-01-01

    Transgenic tumour necrosis factor alpha (TNFα)-driven models of polyarthritis such as the TNFΔARE mouse have proven to be invaluable in delineating aspects of inflammatory disease pathophysiology in humans. Unfortunately, the onset of joint destruction and inflammation in these models represents a significant detriment to breeding management. We examined whether TNFα depleting therapy ‘infliximab’ might represent a significant refinement in routine breeding. Clinical scores of joint inflammation were assessed in TNFΔARE males receiving either infliximab (10 mg/kg) or saline by twice-weekly intraperitoneal injection. Joint histology and bone morphology were assessed by histological analysis and micro-computed tomography (CT), respectively. Analysis of breeding was examined retrospectively in TNFΔARE males prior to, and following, regular introduction of infliximab. Clinical scores of inflammation were significantly reduced in TNFΔARE males receiving infliximab (control 6.6 arbitrary units [AU] ± 0.88 versus infliximab 4.4 AU ± 1.4; P pannus invasion and bone erosion by histology and micro-CT were markedly reduced. In the breeding groups, TNFΔARE males receiving infliximab injections sired more litters over their breeding lifespan (control 1.69 ± 0.22 versus infliximab 3.00 ± 0.19; P < 0.005). Furthermore, prior to infliximab, TNFΔARE males had a 26% risk of failing to sire any litters. This was reduced to 7% after the introduction of infliximab. This study is the first to report that regular administration of infliximab is effective at suppressing disease activity and improving animal welfare in TNFΔARE animals. In addition, we have shown that infliximab is highly efficacious in improving breeding behaviour and increasing the number of litters sired by TNFΔARE males. PMID:28480797

  12. Th17 in Animal Models of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Motomu Hashimoto

    2017-07-01

    Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

  13. Experimental animal models for COPD: a methodological review

    Directory of Open Access Journals (Sweden)

    Vahideh Ghorani

    2017-05-01

    The present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

  14. Animal Cancer Models of Skeletal Metastasis

    Directory of Open Access Journals (Sweden)

    Catherine Hibberd

    2013-01-01

    Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

  15. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  16. The science and necessity of using animal models in the study of necrotizing enterocolitis.

    Science.gov (United States)

    Ares, Guillermo J; McElroy, Steven J; Hunter, Catherine J

    2018-02-01

    Necrotizing enterocolitis (NEC) remains one of the highest causes of mortality and of acute and long-term morbidity in premature infants. Multiple factors are involved in the pathophysiology of NEC including the immaturity of the immune system and the complex changing composition of the intestinal microbiome. This is compounded by the fact that the premature infant should ideally still be a developing fetus and has an immature intestinal tract. Because these complexities are beyond the scope of studies in single-cell cultures, animal models are absolutely essential to understand the mechanisms involved in the pathophysiology of NEC and the effects of inflammation on the immature intestinal tract. To this end, investigators have utilized many different species (e.g., rats, mice, rabbits, quails, piglets, and non-human primates) and conditions to develop models of NEC. Each animal has distinct advantages and drawbacks related to its preterm viability, body size, genetic variability, and cost. The choice of animal model is strongly influenced by the scientific question being addressed. While no model perfectly mimics human NEC, each has greatly improved our understanding of disease. Examples of recent discoveries in NEC pathogenesis and prevention underscore the importance of continued animal research in NEC. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Large Mammalian Animal Models of Heart Disease

    Directory of Open Access Journals (Sweden)

    Paula Camacho

    2016-10-01

    Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.

  18. Animal models for evaluation of oral delivery of biopharmaceuticals

    DEFF Research Database (Denmark)

    Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

    2017-01-01

    of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

  19. Animal models for HIV/AIDS research

    Science.gov (United States)

    Hatziioannou, Theodora; Evans, David T.

    2015-01-01

    The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

  20. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

    2013-01-01

    Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...

  1. Optogenetics in animal model of alcohol addiction

    Science.gov (United States)

    Nalberczak, Maria; Radwanska, Kasia

    2014-11-01

    Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.

  2. Animal Models of Diverticulosis: Review and Recommendations.

    Science.gov (United States)

    Patel, Bhavesh; Guo, Xiaomei; Noblet, Jillian; Chambers, Sean; Kassab, Ghassan S

    2018-06-01

    Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis.

  3. Stop staring facial modeling and animation done right

    CERN Document Server

    Osipa, Jason

    2010-01-01

    The de facto official source on facial animation—now updated!. If you want to do character facial modeling and animation at the high levels achieved in today's films and games, Stop Staring: Facial Modeling and Animation Done Right, Third Edition , is for you. While thoroughly covering the basics such as squash and stretch, lip syncs, and much more, this new edition has been thoroughly updated to capture the very newest professional design techniques, as well as changes in software, including using Python to automate tasks.: Shows you how to create facial animation for movies, games, and more;

  4. The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Sagvolden Terje

    2006-12-01

    Full Text Available Abstract Background ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR, shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR prefrontal cortex, norepinephrine concentrations are elevated. The noradrenergic system appears to be hyperactive as a result of impaired alpha-2A adrenoceptor regulation. Thus, the present study tested behavioral effects of the centrally acting alpha-2A adrenoceptor agonist guanfacine on SHR behavior. Methods The present study tested behavioral effects of guanfacine at doses of 0.075, 0.15, 0.30 and 0.60 mg base/kg i.p. in both male SHRs and their controls, the Wistar Kyoto rat (WKY. ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Results The striking impulsiveness, overactivity, and reduced sustained attention during baseline conditions in the SHR improved by treatment with guanfacine. The most pronounced improvement in SHR behavior was seen following the two highest doses (0.3 and 0.6 mg/kg of guanfacine when SHR behaviors virtually normalized. The positive effects of the drug were most marked towards the end of the session. Conclusion The results indicate that guanfacine improved poor noradrenergic modulation of neuronal circuits that involve the frontal lobes in an animal model of ADHD. The present results support the beneficial effects of guanfacine on ADHD behavior reported clinically and experimentally in primate

  5. Shigella vaccine development: prospective animal models and current status.

    Science.gov (United States)

    Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong

    2013-01-01

    Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.

  6. Real-time classification of humans versus animals using profiling sensors and hidden Markov tree model

    Science.gov (United States)

    Hossen, Jakir; Jacobs, Eddie L.; Chari, Srikant

    2015-07-01

    Linear pyroelectric array sensors have enabled useful classifications of objects such as humans and animals to be performed with relatively low-cost hardware in border and perimeter security applications. Ongoing research has sought to improve the performance of these sensors through signal processing algorithms. In the research presented here, we introduce the use of hidden Markov tree (HMT) models for object recognition in images generated by linear pyroelectric sensors. HMTs are trained to statistically model the wavelet features of individual objects through an expectation-maximization learning process. Human versus animal classification for a test object is made by evaluating its wavelet features against the trained HMTs using the maximum-likelihood criterion. The classification performance of this approach is compared to two other techniques; a texture, shape, and spectral component features (TSSF) based classifier and a speeded-up robust feature (SURF) classifier. The evaluation indicates that among the three techniques, the wavelet-based HMT model works well, is robust, and has improved classification performance compared to a SURF-based algorithm in equivalent computation time. When compared to the TSSF-based classifier, the HMT model has a slightly degraded performance but almost an order of magnitude improvement in computation time enabling real-time implementation.

  7. Animal Models for the Study of Female Sexual Dysfunction

    Science.gov (United States)

    Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

    2017-01-01

    Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain

  8. [Animal models of autoimmune prostatitis and their evaluation criteria].

    Science.gov (United States)

    Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

    2016-03-01

    Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

  9. Improving animal health and livestock productivity to reduce poverty.

    Science.gov (United States)

    Pradère, J-P

    2014-12-01

    This study is based on scientific publications, statistics and field observations. It shows the importance of livestock in the economy and in the risk management strategies implemented by poor farming households. A comparison of livestock performance trends with the evolution of rural poverty in developing countries indicates that growth in livestock production alone is not enough to reduce rural poverty. To help reduce poverty, sustainable production should be based on productivity gains. Prerequisites for improving productivity include better public policies, enhanced research and the reduction of animal disease risk. The study draws attention to the economic, social and environmental consequences of inadequate support for animal health and production in the least developed countries, especially those of sub-Saharan Africa.

  10. Animal Models of Tick-Borne Hemorrhagic Fever Viruses

    Directory of Open Access Journals (Sweden)

    Heinz Feldmann

    2013-05-01

    Full Text Available Tick-borne hemorrhagic fever viruses (TBHFV are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health.

  11. Animal Models of Zika Virus

    Science.gov (United States)

    Bradley, Michael P; Nagamine, Claude M

    2017-01-01

    Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753

  12. Human-animal relationships: from daily life to animal-assisted therapies

    Directory of Open Access Journals (Sweden)

    Marine Grandgeorge

    2011-12-01

    Full Text Available Humans have a long history of relationship with domestic animals and nowadays pets often act as "social substitutes" through bonding. There is some evidence that pet presence at home may induce well being in people and the development of social skills in children. Animal assisted therapies aim at developing these skills in patients on the basis of human animal interactions. Experimental data obtained on animal models suggest that this is indeed a promising line. There is however a lack of clear scientific data that would help defines what the most appropriate procedures or species may be. Improvements are observed, but again sound scientific data are mostly missing. Attention must be given to the welfare of the animals being used.

  13. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

    This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

  14. The Use of Animal Models in Behavioural Neuroscience Research

    NARCIS (Netherlands)

    Bovenkerk, B.; Kaldewaij, F.

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

  15. The Use of Animal Models in Behavioural Neuroscience Research.

    NARCIS (Netherlands)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are

  16. Animal models of contraception: utility and limitations

    Directory of Open Access Journals (Sweden)

    Liechty ER

    2015-04-01

    Full Text Available Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. Keywords: nonhuman primate, preclinical, in vivo, contraceptive devices

  17. Improvement of animal production through research using radioisotopes and radiation

    International Nuclear Information System (INIS)

    1976-01-01

    High birth rates coupled with greater longevity continue to increase the.world's population, especially in the less developed countries. The prevention of undernutrition and ultimately starvation will only be averted by increased food production and more efficient use of that food. At the same time people who have largely subsisted upon plant food diets and whose standards of living are rising, want to increase the use of animal products in order to upgrade their diets. To provide this high quality food animal scientists must find ways of increasing the supply especially in the less developed countries. Since most of the available pasture lands are presently being fully utilized or overgrazed, improved efficiency of the present herds and use of agroindustrial wastes are the only methods left to increase production significantly. The use of radioisotopes and radiation in research are making major contributions to the understanding of the processes necessary to achieve better animal production. In order to provide a forum for exchange of information in this field, the FAO/IAEA Joint Division of Atomic Energy in Food and Agriculture organized an international symposium, held in Vienna, from 2?6 February, on the use of nuclear techniques in animal production. Among the topics discussed at the symposium were: Soil-plant-animal relations regarding minerals, Trace elements in animal nutrition, Calcium, phosphorus and magnesium metabolism, Protein (nitrogen) metabolism - ruminants Protein (nitrogen) metabolism - non-ruminants Nuclear techniques in the control of parasitic infections Animal endocrinology with special emphasis on radioimmunoassays

  18. Improvement of animal production through research using radioisotopes and radiation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1976-07-01

    High birth rates coupled with greater longevity continue to increase the.world's population, especially in the less developed countries. The prevention of undernutrition and ultimately starvation will only be averted by increased food production and more efficient use of that food. At the same time people who have largely subsisted upon plant food diets and whose standards of living are rising, want to increase the use of animal products in order to upgrade their diets. To provide this high quality food animal scientists must find ways of increasing the supply especially in the less developed countries. Since most of the available pasture lands are presently being fully utilized or overgrazed, improved efficiency of the present herds and use of agroindustrial wastes are the only methods left to increase production significantly. The use of radioisotopes and radiation in research are making major contributions to the understanding of the processes necessary to achieve better animal production. In order to provide a forum for exchange of information in this field, the FAO/IAEA Joint Division of Atomic Energy in Food and Agriculture organized an international symposium, held in Vienna, from 2?6 February, on the use of nuclear techniques in animal production. Among the topics discussed at the symposium were: Soil-plant-animal relations regarding minerals, Trace elements in animal nutrition, Calcium, phosphorus and magnesium metabolism, Protein (nitrogen) metabolism - ruminants Protein (nitrogen) metabolism - non-ruminants Nuclear techniques in the control of parasitic infections Animal endocrinology with special emphasis on radioimmunoassays.

  19. Improvement of the performance of animal crossing warning signs.

    Science.gov (United States)

    Khalilikhah, Majid; Heaslip, Kevin

    2017-09-01

    Animal-vehicle collisions (AVCs) can result in serious injury and death to drivers, animals' death, and significant economic costs. However, the cost effectiveness of the majority of AVC mitigation measures is a significant issue. A mobile-based data collection effort was deployed to measure signs under the Utah Department of Transportation's (UDOT) jurisdiction. The crash data were obtained from the UDOT risk management database. ArcGIS was employed to link these two data sets and extract animal-related crashes and signs. An algorithm was developed to process the data and identify AVCs that occurred within sign recognition distance. Kernel density estimation (KDE) technique was applied to identify potential crash hotspots. Only 2% of AVCs occurred within the recognition distance of animal crossing signs. Almost 58% of animal-related crashes took place on the Interstate and U.S. highways, wherein only 30% of animal crossing signs were installed. State routes with a higher average number of signs experienced a lower number of AVCs per mile. The differences between AVCs that occurred within versus outside of sign recognition distance were not statistically significant regarding crash severity, time of crash, weather condition, driver age, vehicle speed, and type of animal. It is more likely that drivers become accustomed to deer crossing signs than cow signs. Based on the historical crash data and landscape structure, with attention given to the low cost safety improvement methods, a combination of different types of AVC mitigation measures can be developed to reduce the number of animal-related crashes. After an in-depth analysis of AVC data, warning traffic signs, coupled with other low cost mitigation countermeasures can be successfully placed in areas with higher priority or in critical areas. Practical applications: The findings of this study assist transportation agencies in developing more efficient mitigation measures against AVCs. Copyright © 2017 National

  20. Animating climate model data

    Science.gov (United States)

    DaPonte, John S.; Sadowski, Thomas; Thomas, Paul

    2006-05-01

    This paper describes a collaborative project conducted by the Computer Science Department at Southern Connecticut State University and NASA's Goddard Institute for Space Science (GISS). Animations of output from a climate simulation math model used at GISS to predict rainfall and circulation have been produced for West Africa from June to September 2002. These early results have assisted scientists at GISS in evaluating the accuracy of the RM3 climate model when compared to similar results obtained from satellite imagery. The results presented below will be refined to better meet the needs of GISS scientists and will be expanded to cover other geographic regions for a variety of time frames.

  1. Aspects of animal models for major neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Lefter Radu

    2014-01-01

    Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

  2. Immunogenicity of therapeutic proteins: the use of animal models.

    Science.gov (United States)

    Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

    2011-10-01

    Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

  3. Cardiovascular Imaging: What Have We Learned From Animal Models?

    Directory of Open Access Journals (Sweden)

    Arnoldo eSantos

    2015-10-01

    Full Text Available Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a nondestructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, i the technical development of different imaging tools, ii to test hypothesis generated from human studies and finally, iii to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.

  4. Animal models of GM2 gangliosidosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Lawson CA

    2016-07-01

    Full Text Available Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease

  5. Realistic Modeling and Animation of Human Body Based on Scanned Data

    Institute of Scientific and Technical Information of China (English)

    Yong-You Ma; Hui Zhang; Shou-Wei Jiang

    2004-01-01

    In this paper we propose a novel method for building animation model of real human body from surface scanned data.The human model is represented by a triangular mesh and described as a layered geometric model.The model consists of two layers: the control skeleton generating body animation from motion capture data,and the simplified surface model providing an efficient representation of the skin surface shape.The skeleton is generated automatically from surface scanned data using the feature extraction,and thena point-to-line mapping is used to map the surface model onto the underlying skeleton.The resulting model enables real-time and smooth animation by manipulation of the skeleton while maintaining the surface detail.Compared with earlier approach,the principal advantages of our approach are the automated generation of body control skeletons from the scanned data for real-time animation,and the automatic mapping and animation of the captured human surface shape.The human model constructed in this work can be used for applications of ergonomic design,garment CAD,real-time simulating humans in virtual reality environment and so on.

  6. Requirements for laboratory animals in health programmes*

    OpenAIRE

    Held, J. R.

    1981-01-01

    Laboratory animals are essential for the successful execution of many health programmes. A wide variety of animal models is used in the worldwide efforts to improve the control of various diseases, and in the basic research needed to improve health care. Biomedical programmes require specially-bred animals reared under controlled conditions, with close attention given to such factors as physical environment, nutrition, microbiological status, and genetic background. The need for a regular sup...

  7. Reflected stochastic differential equation models for constrained animal movement

    Science.gov (United States)

    Hanks, Ephraim M.; Johnson, Devin S.; Hooten, Mevin B.

    2017-01-01

    Movement for many animal species is constrained in space by barriers such as rivers, shorelines, or impassable cliffs. We develop an approach for modeling animal movement constrained in space by considering a class of constrained stochastic processes, reflected stochastic differential equations. Our approach generalizes existing methods for modeling unconstrained animal movement. We present methods for simulation and inference based on augmenting the constrained movement path with a latent unconstrained path and illustrate this augmentation with a simulation example and an analysis of telemetry data from a Steller sea lion (Eumatopias jubatus) in southeast Alaska.

  8. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  9. Behavioral models of tinnitus and hyperacusis in animals

    Directory of Open Access Journals (Sweden)

    Sarah H Hayes

    2014-09-01

    Full Text Available The phantom perception of tinnitus and reduced sound level tolerance associated with hyperacusis, have a high comorbidity and can be debilitating conditions for which there are no widely accepted treatments. One factor limiting the development of treatments for tinnitus and hyperacusis is the lack of reliable animal behavioral models of these disorders. Therefore, the purpose of this review is to highlight the current animal models of tinnitus and hyperacusis, and to detail the advantages and disadvantages of each paradigm. To date, this is the first review to include models of both tinnitus and hyperacusis.

  10. Systems Biology in Animal Production and Health

    DEFF Research Database (Denmark)

    for improved animal production and health. The book will contain online resources where additional data and programs can be accessed. Some chapters also come with computer programming codes and example datasets to provide readers hands-on (computer) exercises. This second volume deals with integrated modeling...... and analyses of multi-omics datasets from theoretical and computational approaches and presents their applications in animal production and health as well as veterinary medicine to improve diagnosis, prevention and treatment of animal diseases. This book is suitable for both students and teachers in animal...

  11. Experimental study on oral sulfhydryl as an adjuvant for improving nitrate ester tolerance in an animal model.

    Science.gov (United States)

    Chen, L; Jiang, J-Q; Zhang, Y; Feng, H

    2018-03-01

    As an initial step in exploring the feasibility of oral sulfhydryl as an adjuvant for improving nitrate ester tolerance, this study was designed to experimentally test the adjuvant therapy in a rabbit model of atherosclerosis (AS). New Zealand white rabbits with induced AS were randomly divided into four groups: AS group, AS + nitrate ester group, AS + nitrate ester tolerance group, and AS + drug combination group. Additionally, four equivalent groups with healthy New Zealand white rabbits without AS were also conformed. After feeding the animals for 5 days, the concentrations of superoxide anion (•O2-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in blood and the relaxation response of the aortic ring were determined in each subject. The vascular plaques in different treatment groups were assessed by Hematoxylin and eosin (HE) staining to investigate the therapeutic value of sulfhydryl as coadjuvant for improving nitrate ester tolerance, and changes in blood vessels in different treatment groups were studied by immunohistochemical assays. Our results showed no significant differences through time in the concentrations of •O2-, SOD, MDA, NO, ET-1 between the healthy control and the nitrate ester groups (p > 0.05). The levels of SOD and MDA in the nitrate ester tolerance group increased with time, however, the levels of •O2-, NO and ET-1 decreased gradually (p tolerance groups were significantly decreased, but SOD and MDA were significantly increased (p tolerance, and this strategy was safe and looks promising for humans.

  12. A systematic review and meta-analysis of acupuncture for improving learning and memory ability in animals.

    Science.gov (United States)

    Huang, Kai-Yu; Liang, Shuang; Yu, Mei-Ling; Fu, Shu-Ping; Chen, Xia; Lu, Sheng-Feng

    2016-08-19

    Memory loss is the most prominent symptoms of brain aging, but there is currently no evidence-based treatment strategy. Acupuncture has been widely used in China and the effectiveness for improving learning and memory has been mentioned in previous studies. We conducted this systematic review and meta-analysis to evaluate the effectiveness of acupuncture for improving learning and memory in animal experiments. We searched Pubmed, Embase, Ovid Medline(R), the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and Wanfang data Information Site to collect studies published up to December 2015. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measure is Morris water maze. A meta-analysis was conducted according to the Cochrane systematic review method by using RevMan 5.3 software. Forty-two studies involving 944 animals were included. The quality score of the studies ranged from 2 to 8, with a mean of 5.3. Meta-analysis results showed that 24 studies reported significant effect of acupuncture for decreasing escape latency (-3.00, 95 % CI: -3.78 ~ -2.23, P learning and memory ability in animal models, suggesting it as a candidate therapy for memory loss of aged brain.

  13. Technical Note: How to use Winbugs to infer animal models

    DEFF Research Database (Denmark)

    Damgaard, Lars Holm

    2007-01-01

    This paper deals with Bayesian inferences of animal models using Gibbs sampling. First, we suggest a general and efficient method for updating additive genetic effects, in which the computational cost is independent of the pedigree depth and increases linearly only with the size of the pedigree....... Second, we show how this approach can be used to draw inferences from a wide range of animal models using the computer package Winbugs. Finally, we illustrate the approach in a simulation study, in which the data are generated and analyzed using Winbugs according to a linear model with i.i.d errors...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...

  14. Impact of Relationships between Test and Reference Animals and between Reference Animals on Reliability of Genomic Prediction

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Lund, Mogens Sandø; Sun, Dongxiao

    This study investigated reliability of genomic prediction in various scenarios with regard to relationship between test and reference animals and between animals within the reference population. Different reference populations were generated from EuroGenomics data and 1288 Nordic Holstein bulls...... as a common test population. A GBLUP model and a Bayesian mixture model were applied to predict Genomic breeding values for bulls in the test data. Result showed that a closer relationship between test and reference animals led to a higher reliability, while a closer relationship between reference animal...... resulted in a lower reliability. Therefore, the design of reference population is important for improving the reliability of genomic prediction. With regard to model, the Bayesian mixture model in general led to slightly a higher reliability of genomic prediction than the GBLUP model...

  15. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

  16. Use of soft hydrothermal processing to improve and recycle bedding for laboratory animals.

    Science.gov (United States)

    Miyamoto, T; Li, Z; Kibushi, T; Yamasaki, N; Kasai, N

    2008-10-01

    Cage bedding for laboratory rodents can influence animal wellbeing and thus the experimental data. In addition, a large amount of used bedding containing excrement is discharged as medical waste from life science institutes and breeding companies. We developed a ground-breaking system to improve fresh bedding and recycle used bedding by applying a soft hydrothermal process with high-temperature and high-pressure dry steam. The system removes both harmful organic components and aromatic hydrocarbons that can affect animals' metabolism. The purpose of the present study was to evaluate the chemical and physical properties of the improved fresh bedding and the recycled used bedding treated by the system. The results showed that 68-99% of the predominant aromatic hydrocarbons were removed from fresh bedding treated at 0.35 MPa and 140 degrees C for 120 min ('improved bedding'). In addition, 59.4-99.0% of predominant harmful organic compounds derived from excrement were removed from used bedding treated at 0.45 MPa and 150 degrees C for 60 min ('recycled bedding'). The soft hydrothermal treatment increased the number of acidic functional groups on the bedding surface and gave it the high adsorptive efficiency of ammonia gas. Harmful substances such as microorganisms, heavy metals and pesticides decreased below the detection limit. The results clearly showed that the improved and recycled bedding is safer for laboratory rodents and has the potential to ameliorate conditions in primary and secondary enclosures (e.g. cages and animal rooms) used for maintaining laboratory animals. This process may be one of the most advanced techniques in providing an alternative to softwood and other bedding, economizing through the recycling of used bedding and reducing bedding waste from animal facilities.

  17. Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

    Science.gov (United States)

    Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

    2010-06-01

    Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

  18. Stress urinary incontinence animal models as a tool to study cell-based regenerative therapies targeting the urethral sphincter.

    Science.gov (United States)

    Herrera-Imbroda, Bernardo; Lara, María F; Izeta, Ander; Sievert, Karl-Dietrich; Hart, Melanie L

    2015-03-01

    Urinary incontinence (UI) is a major health problem causing a significant social and economic impact affecting more than 200million people (women and men) worldwide. Over the past few years researchers have been investigating cell therapy as a promising approach for the treatment of stress urinary incontinence (SUI) since such an approach may improve the function of a weakened sphincter. Currently, a diverse collection of SUI animal models is available. We describe the features of the different models of SUI/urethral dysfunction and the pros and cons of these animal models in regard to cell therapy applications. We also discuss different cell therapy approaches and cell types tested in preclinical animal models. Finally, we propose new research approaches and perspectives to ensure the use of cellular therapy becomes a real treatment option for SUI. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

    Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural

  20. Rodent stereotaxic surgery and animal welfare outcome improvements for behavioral neuroscience.

    Science.gov (United States)

    Fornari, Raquel V; Wichmann, Romy; Atsak, Piray; Atucha, Erika; Barsegyan, Areg; Beldjoud, Hassiba; Messanvi, Fany; Thuring, Catriene M A; Roozendaal, Benno

    2012-01-30

    Stereotaxic surgery for the implantation of cannulae into specific brain regions has for many decades been a very successful experimental technique to investigate the effects of locally manipulated neurotransmitter and signaling pathways in awake, behaving animals. Moreover, the stereotaxic implantation of electrodes for electrophysiological stimulation and recording studies has been instrumental to our current understanding of neuroplasticity and brain networks in behaving animals. Ever-increasing knowledge about optimizing surgical techniques in rodents(1-4), public awareness concerning animal welfare issues and stringent legislation (e.g., the 2010 European Union Directive on the use of laboratory animals(5)) prompted us to refine these surgical procedures, particularly with respect to implementing new procedures for oxygen supplementation and the continuous monitoring of blood oxygenation and heart rate levels during the surgery as well as introducing a standardized protocol for post-surgical care. Our observations indicate that these modifications resulted in an increased survival rate and an improvement in the general condition of the animals after surgery (e.g. less weight loss and a more active animal). This video presentation will show the general procedures involved in this type of stereotaxic surgery with special attention to our several modifications. We will illustrate these surgical procedures in rats, but it is also possible to perform this type of surgery in mice or other small laboratory animals by using special adaptors for the stereotaxic apparatus(6).

  1. Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

    Science.gov (United States)

    Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

    2010-06-01

    Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

  2. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    Energy Technology Data Exchange (ETDEWEB)

    Vamathevan, Jessica J., E-mail: jessica.j.vamathevan@gsk.com [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)

    2013-07-15

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.

  3. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    International Nuclear Information System (INIS)

    Vamathevan, Jessica J.; Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M.; Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli; Kenny, Steve; Brown, James R.; Huxley-Jones, Julie; Lyon, Jon; Haselden, John; Min, Jiumeng; Sanseau, Philippe

    2013-01-01

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns

  4. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  5. Animal models for Ebola and Marburg virus infections

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  6. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

    Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  7. Precise MRI-based stereotaxic surgery in large animal models

    DEFF Research Database (Denmark)

    Glud, Andreas Nørgaard; Bech, Johannes; Tvilling, Laura

    BACKGROUND: Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical...... and subcortical anatomical differences. NEW METHOD: We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulphate solution or MRI-visible paste from a commercially available...... cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. RESULTS: Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. COMPARISON...

  8. Estimating abundance of an open population with an N-mixture model using auxiliary data on animal movements.

    Science.gov (United States)

    Ketz, Alison C; Johnson, Therese L; Monello, Ryan J; Mack, John A; George, Janet L; Kraft, Benjamin R; Wild, Margaret A; Hooten, Mevin B; Hobbs, N Thompson

    2018-04-01

    Accurate assessment of abundance forms a central challenge in population ecology and wildlife management. Many statistical techniques have been developed to estimate population sizes because populations change over time and space and to correct for the bias resulting from animals that are present in a study area but not observed. The mobility of individuals makes it difficult to design sampling procedures that account for movement into and out of areas with fixed jurisdictional boundaries. Aerial surveys are the gold standard used to obtain data of large mobile species in geographic regions with harsh terrain, but these surveys can be prohibitively expensive and dangerous. Estimating abundance with ground-based census methods have practical advantages, but it can be difficult to simultaneously account for temporary emigration and observer error to avoid biased results. Contemporary research in population ecology increasingly relies on telemetry observations of the states and locations of individuals to gain insight on vital rates, animal movements, and population abundance. Analytical models that use observations of movements to improve estimates of abundance have not been developed. Here we build upon existing multi-state mark-recapture methods using a hierarchical N-mixture model with multiple sources of data, including telemetry data on locations of individuals, to improve estimates of population sizes. We used a state-space approach to model animal movements to approximate the number of marked animals present within the study area at any observation period, thereby accounting for a frequently changing number of marked individuals. We illustrate the approach using data on a population of elk (Cervus elaphus nelsoni) in Northern Colorado, USA. We demonstrate substantial improvement compared to existing abundance estimation methods and corroborate our results from the ground based surveys with estimates from aerial surveys during the same seasons. We develop a

  9. [RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

    Science.gov (United States)

    Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

    2015-12-01

    To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

  10. Is it acceptable to use animals to model obese humans?

    DEFF Research Database (Denmark)

    Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.

    2014-01-01

    Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments f...

  11. Animal Models of Schizophrenia with a Focus on Models Targeting NMDA Receptors

    Czech Academy of Sciences Publication Activity Database

    Svojanovská, Markéta; Stuchlík, Aleš

    2015-01-01

    Roč. 4, č. 1 (2015), s. 3-18 ISSN 1805-7225 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : schizophrenia * animal models * pharmacological models * genetic models * neurodevelopmental models * preclinical studies Subject RIV: FH - Neurology

  12. Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

    Science.gov (United States)

    Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

    2015-04-01

    Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  13. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

  14. Animal Models Utilized in HTLV-1 Research

    Directory of Open Access Journals (Sweden)

    Amanda R. Panfil

    2013-01-01

    Full Text Available Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1 over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP. Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, “humanized” mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.

  15. Do Bone Graft and Cracking of the Sclerotic Cavity Improve Fixation of Titanium and Hydroxyapatite-coated Revision Implants in an Animal Model?

    Science.gov (United States)

    Elmengaard, Brian; Baas, Joergen; Jakobsen, Thomas; Kold, Soren; Jensen, Thomas B; Bechtold, Joan E; Soballe, Kjeld

    2017-02-01

    We previously introduced a manual surgical technique that makes small perforations (cracks) through the sclerotic bone shell that typically forms during the process of aseptic loosening ("crack" revision technique). Perforating just the shell (without violating the proximal cortex) can maintain overall bone continuity while allowing marrow and vascular elements to access the implant surface. Because many revisions require bone graft to fill defects, we wanted to determine if bone graft could further increase implant fixation beyond what we have experimentally shown with the crack technique alone. Also, because both titanium (Ti6Al4V) and hydroxyapatite (HA) implant surfaces are used in revisions, we also wanted to determine their relative effectiveness in this model. We hypothesized that both (1) allografted plasma-sprayed Ti6Al4V; and (2) allografted plasma-sprayed HA-coated implants inserted with a crack revision technique have better fixation compared with a noncrack revision technique in each case. Under approval from our Institutional Animal Care and Use Committee, a female canine animal model was used to evaluate the uncemented revision technique (crack, noncrack) using paired contralateral implants while implant surface (Ti6Al4V, HA) was qualitatively compared between the two (unpaired) series. All groups received bone allograft tightly packed around the implant. This revision model includes a cylindrical implant pistoning 500 μm in a 0.75-mm gap, with polyethylene particles, for 8 weeks. This engenders a bone and tissue response representative of the metaphyseal cancellous region of an aseptically loosened component. At 8 weeks, the original implants were revised and followed for an additional 4 weeks. Mechanical fixation was assessed by load, stiffness, and energy to failure when loaded in axial pushout. Histomorphometry was used to determine the amount and location of bone and fibrous tissue in the grafted gap. The grafted crack revision improved

  16. Animal models used for testing hydrogels in cartilage regeneration.

    Science.gov (United States)

    Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

    2018-05-14

    Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. The Nuremberg Code subverts human health and safety by requiring animal modeling

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-07-01

    Full Text Available Abstract Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

  18. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time...

  19. Applications of gene-based technologies for improving animal production and health in developing countries

    International Nuclear Information System (INIS)

    Makkar, H.P.S.; Viljoen, G.J.

    2005-01-01

    This book provides a compilation of peer-reviewed scientific contributions from authoritative researchers attending an international symposium convened by the Animal Production and Health Sub-programme of the Animal Production and Health (APH), Joint FAO/IAEA Programme in cooperation with the Animal Production and Health Division of the FAO. These Proceedings contain invaluable information on the role and future potential of gene-based technologies for improving animal production and health, possible applications and constraints in the use of this technology in developing countries and their specific research needs

  20. Advancing research on animal-transported subsidies by integrating animal movement and ecosystem modelling.

    Science.gov (United States)

    Earl, Julia E; Zollner, Patrick A

    2017-09-01

    Connections between ecosystems via animals (active subsidies) support ecosystem services and contribute to numerous ecological effects. Thus, the ability to predict the spatial distribution of active subsidies would be useful for ecology and conservation. Previous work modelling active subsidies focused on implicit space or static distributions, which treat passive and active subsidies similarly. Active subsidies are fundamentally different from passive subsidies, because animals can respond to the process of subsidy deposition and ecosystem changes caused by subsidy deposition. We propose addressing this disparity by integrating animal movement and ecosystem ecology to advance active subsidy investigations, make more accurate predictions of subsidy spatial distributions, and enable a mechanistic understanding of subsidy spatial distributions. We review selected quantitative techniques that could be used to accomplish integration and lead to novel insights. The ultimate objective for these types of studies is predictions of subsidy spatial distributions from characteristics of the subsidy and the movement strategy employed by animals that transport subsidies. These advances will be critical in informing the management of ecosystem services, species conservation and ecosystem degradation related to active subsidies. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  1. Genomics to benefit livestock production: improving animal health

    Directory of Open Access Journals (Sweden)

    Graham Stuart Plastow

    2016-06-01

    Full Text Available ABSTRACT The primary principle underlying the application of genomics is that it has the most value for difficult and expensive to measure traits. These traits will differ between species and probably also between markets. Maintenance of health will be one of the biggest challenges for efficient livestock production in the next few decades. This challenge will only increase in the face of demand for animal protein, resistance to existing drugs, and the pressure to reduce the use of antibiotics in agriculture. There is probably genetic variation in susceptibility for all diseases but little has been done to make use of this variation to date. In part this is because it is very difficult as well as expensive to measure this variation. This suggests that genomics should provide one of the ways of tackling the challenge of improving animal health. This paper will discuss the concepts of resistance, variation in susceptibility, and resilience; provide examples and present some recent results in cattle and pigs; and briefly discuss the application of gene editing in relation to disease resistance.

  2. The Efficacy of Trastuzumab in Animal Models of Breast Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jiarong Chen

    Full Text Available Breast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2. To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer.We searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias.We included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%. Median survival was prolonged by a factor of 1.45 (1.30-1.62. Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias.We have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.

  3. NAFLD, Estrogens, and Physical Exercise: The Animal Model

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lavoie

    2012-01-01

    Full Text Available One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.

  4. Animal models to study plaque vulnerability

    NARCIS (Netherlands)

    Schapira, K.; Heeneman, S.; Daemen, M. J. A. P.

    2007-01-01

    The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture,

  5. Animal Models for Tuberculosis in Translational and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Lingjun Zhan

    2017-05-01

    Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.

  6. Animal model for hepatitis C virus infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2015-01-01

    Hepatitis C virus (HCV) infects more than 170 million people in the world and chronic HCV infection develops into cirrhosis and hepatocellular carcinoma (HCC). Recently, the effective compounds have been approved for HCV treatment, the protease inhibitor and polymerase inhibitor (direct acting antivirals; DAA). DAA-based therapy enabled to cure from HCV infection. However, development of new drug and vaccine is still required because of the generation of HCV escape mutants from DAA, development of HCC after treatment of DAA, and the high cost of DAA. In order to develop new anti-HCV drug and vaccine, animal infection model of HCV is essential. In this manuscript, we would like to introduce the history and the current status of the development of HCV animal infection model.

  7. Deformation Models Tracking, Animation and Applications

    CERN Document Server

    Torres, Arnau; Gómez, Javier

    2013-01-01

    The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications.  The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...

  8. Perinatal Hypoxia and Ischemia in Animal Models of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Dimitri Hefter

    2018-03-01

    Full Text Available Intrauterine or perinatal complications constitute a major risk for psychiatric diseases. Infants who suffered from hypoxia–ischemia (HI are at twofold risk to develop schizophrenia in later life. Several animal models attempt to reproduce these complications to study the yet unknown steps between an insult in early life and outbreak of the disease decades later. However, it is very challenging to find the right type and severity of insult leading to a disease-like phenotype in the animal, but not causing necrosis and focal neurological deficits. By contrast, too mild, repetitive insults may even be protective via conditioning effects. Thus, it is not surprising that animal models of hypoxia lead to mixed results. To achieve clinically translatable findings, better protocols are urgently needed. Therefore, we compare widely used models of hypoxia and HI and propose future directions for the field.

  9. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

  10. [New advances in animal transgenic technology].

    Science.gov (United States)

    Sun, Zhen-Hong; Miao, Xiang-Yang; Zhu, Rui-Liang

    2010-06-01

    Animal transgenic technology is one of the fastest growing biotechnology in the 21st century. It is used to integrate foreign genes into the animal genome by genetic engineering technology so that foreign genes can be expressed and inherited to the offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors on preparation of transgenic animals. A variety of transgenic techniques are available, each of which has its own advantages and disadvantages and still needs further study because of unresolved technical and safety issues. With the in-depth research, the transgenic technology will have broad application prospects in the fields of exploration of gene function, animal genetic improvement, bioreactor, animal disease models, organ transplantation and so on. This article reviews the recently developed animal gene transfer techniques, including germline stem cell mediated method to improve the efficiency, gene targeting to improve the accuracy, RNA interference (RNAi)-mediated gene silencing technology, and the induced pluripotent stem cells (iPS) transgenic technology. The new transgenic techniques can provide a better platform for the study of trans-genic animals and promote the development of medical sciences, livestock production, and other fields.

  11. Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition

    Science.gov (United States)

    Woodward, Bill

    2016-01-01

    Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition. PMID:27077845

  12. Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition.

    Science.gov (United States)

    Woodward, Bill

    2016-04-11

    Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

  13. Biology of Obesity: Lessons from Animal Models of Obesity

    Directory of Open Access Journals (Sweden)

    Keizo Kanasaki

    2011-01-01

    problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

  14. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  15. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  16. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  17. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    Science.gov (United States)

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Microscopic transport model animation visualisation on KML base

    Science.gov (United States)

    Yatskiv, I.; Savrasovs, M.

    2012-10-01

    By reading classical literature devoted to the simulation theory it could be found that one of the greatest possibilities of simulation is the ability to present processes inside the system by animation. This gives to the simulation model additional value during presentation of simulation results for the public and authorities who are not familiar enough with simulation. That is why most of universal and specialised simulation tools have the ability to construct 2D and 3D representation of the model. Usually the development of such representation could take much time and there must be put a lot forces into creating an adequate 3D representation of the model. For long years such well-known microscopic traffic flow simulation software tools as VISSIM, AIMSUN and PARAMICS have had a possibility to produce 2D and 3D animation. But creation of realistic 3D model of the place where traffic flows are simulated, even in these professional software tools it is a hard and time consuming action. The goal of this paper is to describe the concepts of use the existing on-line geographical information systems for visualisation of animation produced by simulation software. For demonstration purposes the following technologies and tools have been used: PTV VISION VISSIM, KML and Google Earth.

  19. Use of spatial capture-recapture modeling and DNA data to estimate densities of elusive animals

    Science.gov (United States)

    Kery, Marc; Gardner, Beth; Stoeckle, Tabea; Weber, Darius; Royle, J. Andrew

    2011-01-01

    Assessment of abundance, survival, recruitment rates, and density (i.e., population assessment) is especially challenging for elusive species most in need of protection (e.g., rare carnivores). Individual identification methods, such as DNA sampling, provide ways of studying such species efficiently and noninvasively. Additionally, statistical methods that correct for undetected animals and account for locations where animals are captured are available to efficiently estimate density and other demographic parameters. We collected hair samples of European wildcat (Felis silvestris) from cheek-rub lure sticks, extracted DNA from the samples, and identified each animals' genotype. To estimate the density of wildcats, we used Bayesian inference in a spatial capture-recapture model. We used WinBUGS to fit a model that accounted for differences in detection probability among individuals and seasons and between two lure arrays. We detected 21 individual wildcats (including possible hybrids) 47 times. Wildcat density was estimated at 0.29/km2 (SE 0.06), and 95% of the activity of wildcats was estimated to occur within 1.83 km from their home-range center. Lures located systematically were associated with a greater number of detections than lures placed in a cell on the basis of expert opinion. Detection probability of individual cats was greatest in late March. Our model is a generalized linear mixed model; hence, it can be easily extended, for instance, to incorporate trap- and individual-level covariates. We believe that the combined use of noninvasive sampling techniques and spatial capture-recapture models will improve population assessments, especially for rare and elusive animals.

  20. Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

    Science.gov (United States)

    Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

    2018-04-05

    Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia.

    Science.gov (United States)

    Cai, Mudan; Lee, Jun Hwan; Yang, Eun Jin

    2017-10-01

    Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 μg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.

  2. An Overview of Animal Models for Arthropod-Borne Viruses.

    Science.gov (United States)

    Reynolds, Erin S; Hart, Charles E; Hermance, Meghan E; Brining, Douglas L; Thangamani, Saravanan

    2017-06-01

    Arthropod-borne viruses (arboviruses) have continued to emerge in recent years, posing a significant health threat to millions of people worldwide. The majority of arboviruses that are pathogenic to humans are transmitted by mosquitoes and ticks, but other types of arthropod vectors can also be involved in the transmission of these viruses. To alleviate the health burdens associated with arbovirus infections, it is necessary to focus today's research on disease control and therapeutic strategies. Animal models for arboviruses are valuable experimental tools that can shed light on the pathophysiology of infection and will enable the evaluation of future treatments and vaccine candidates. Ideally an animal model will closely mimic the disease manifestations observed in humans. In this review, we outline the currently available animal models for several viruses vectored by mosquitoes, ticks, and midges, for which there are no standardly available vaccines or therapeutics.

  3. Reducing the variation in animal models by standardizing the gut microbiota

    DEFF Research Database (Denmark)

    Ellekilde, Merete; Hufeldt, Majbritt Ravn; Hansen, Camilla Hartmann Friis

    2011-01-01

    , a large proportion of laboratory animals are used to study such diseases, but inter-individual variation in these animal models leads to the need for larger group sizes to reach statistical significance and adequate power. By standardizing the microbial and immunological status of laboratory animals we...... mice changed the glucose tolerance without affecting weight or mucosal immunity. Further investigations concerning the mechanisms of how GM influences disease development is necessary, but based on these results it seems reasonable to assume that by manipulating the GM we may produce animal models...... may therefore be able to produce animals with a more standardized response and less variation. This would lead to more precise results and a reduced number of animals needed for statistical significance. Denaturing gradient gel electrophoresis (DGGE) - a culture independent approach separating PCR...

  4. Improvement of the MSG code for the MONJU evaporators. Additional function of reverse flow calculation on water/steam model and animation for post processing

    International Nuclear Information System (INIS)

    Toda, Shin-ichi; Yoshikawa, Shinji; Oketani, Kazuhiro

    2003-05-01

    The improved version of the MSG code (Multi-dimensional Thermal-hydraulic Analysis Code for Steam Generators) has been released. It has been carried out to improve based on the original version in order to calculate reverse flow on water/steam side, and to animate the post-processing data. To calculate reverse flow locally, modification to set pressure at each divided node point of water/steam region in the helical-coil heat transfer tubes has been carried out. And the matrix solver has been also improved to treat a problem within practical calculation time against increasing the pressure points. In this case pressure and enthalpy have to be calculated simultaneously, however, it was found out that using the block-Jacobean method make a diagonal-dominant matrix, and solve the matrix efficiently with a relaxation method. As the result of calculations of a steady-state condition and a transient of SG blow down with manual trip operation, the improvement on calculation function of the MSG code was confirmed. And an animation function of temperature contour in the sodium shell side as a post processing has been added. Since the animation is very effective to understand thermal-hydraulic behavior on the sodium shell side of the SG, especially in case of transient condition, the analysis and evaluation of the calculation results will be enabled to be more quickly and effectively. (author)

  5. Animal models for cancer and uses thereof

    NARCIS (Netherlands)

    Demaria, Marco; Campisi, Judith; van Deursen, Jan M.; Kirkland, James; Tchkonia, Tamara T.; Baker, Darren J.

    2017-01-01

    Non-human animal cancer models are provided herein for identifying and characterizing agents useful for therapy and prophylaxis of cancers, including agents useful for diminishing side effects related to cancer therapies and reducing metastatic disease.

  6. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

    Science.gov (United States)

    McGreevy, Joe W.; Hakim, Chady H.; McIntosh, Mark A.; Duan, Dongsheng

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

  7. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy.

    Science.gov (United States)

    McGreevy, Joe W; Hakim, Chady H; McIntosh, Mark A; Duan, Dongsheng

    2015-03-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. © 2015. Published by The Company of Biologists Ltd.

  8. Animal models of 'anxiety': where next?

    Science.gov (United States)

    Rodgers, R J

    1997-11-01

    Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically

  9. Animal models of tic disorders: a translational perspective.

    Science.gov (United States)

    Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco

    2014-12-30

    Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Animal models of tic disorders: A translational perspective

    Science.gov (United States)

    Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco

    2014-01-01

    Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952

  11. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

    Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645

  12. The contribution of animal models to the study of obesity.

    Science.gov (United States)

    Speakman, John; Hambly, Catherine; Mitchell, Sharon; Król, Elzbieta

    2008-10-01

    Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such genetically-engineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy

  13. Modeling Heat-Transfer in Animal Habitats in the Shuttle Orbiter Middeck

    Science.gov (United States)

    Eodice, Michael T.; Sun, Sid (Technical Monitor)

    2000-01-01

    A mathematical model has been developed to evaluate the heat transfer characteristics of an Animal Enclosure Module (AEM) in the microgravity environment. The AEM is a spaceflight habitat that provides life support for up to six rodents in the Space Shuttle Middeck. Currently, temperatures within the AEM are recorded in real time using a solid state data recorder; however, the data are only available for analysis post-flight. This temperature information is useful for characterizing the thermal environment of the AEM for researchers, but is unavailable during flight operations. Because animal health in microgravity is directly linked to the thermal environment, the ability to predict internal AEM temperatures is extremely useful to life science researchers. NASA flight crews typically carry hand-held temperature measurement devices which allow them to provide ground researchers with near real time readings of AEM inlet temperature; however, higher priority operations limit the frequency at which these measurements can be made and subsequently downlinked. The mathematical model developed allows users to predict internal cage volume temperatures based on knowledge of the ambient air temperature entering the AEM air intake ports. Additionally, an average convective heat transfer coefficient for the AEM has been determined to provide engineers with the requisite information to facilitate future design improvements and product upgrades. The model has been validated using empirical data from a series of three Space Shuttle missions.

  14. The calm mouse: an animal model of stress reduction.

    Science.gov (United States)

    Gurfein, Blake T; Stamm, Andrew W; Bacchetti, Peter; Dallman, Mary F; Nadkarni, Nachiket A; Milush, Jeffrey M; Touma, Chadi; Palme, Rupert; Di Borgo, Charles Pozzo; Fromentin, Gilles; Lown-Hecht, Rachel; Konsman, Jan Pieter; Acree, Michael; Premenko-Lanier, Mary; Darcel, Nicolas; Hecht, Frederick M; Nixon, Douglas F

    2012-05-09

    Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. Therefore, we have developed a "calm mouse model" with caging enhancements designed to reduce murine stress. Male BALB/c mice were divided into four groups: control (Cntl), standard caging; calm (Calm), large caging to reduce animal density, a cardboard nest box for shelter, paper nesting material to promote innate nesting behavior, and a polycarbonate tube to mimic tunneling; control exercise (Cntl Ex), standard caging with a running wheel, known to reduce stress; and calm exercise (Calm Ex), calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited significantly less corticosterone production than Cntl animals. We also observed changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex animals had innate and adaptive immune responses that were more sensitive to acute handling stress than those in Cntl. Calm animals gained greater body mass than Cntl, although they had similar food intake, and we also observed changes in body composition, using magnetic resonance imaging. Together, our results suggest that the Calm mouse model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with existing disease models.

  15. Critical overview of all available animal models for abdominal wall hernia research.

    Science.gov (United States)

    Vogels, R R M; Kaufmann, R; van den Hil, L C L; van Steensel, S; Schreinemacher, M H F; Lange, J F; Bouvy, N D

    2017-10-01

    Since the introduction of the first prosthetic mesh for abdominal hernia repair, there has been a search for the "ideal mesh." The use of preclinical or animal models for assessment of necessary characteristics of new and existing meshes is an indispensable part of hernia research. Unfortunately, in our experience there is a lack of consensus among different research groups on which model to use. Therefore, we hypothesized that there is a lack of comparability within published animal research on hernia surgery due to wide range in experimental setup among different research groups. A systematic search of the literature was performed to provide a complete overview of all animal models published between 2000 and 2014. Relevant parameters on model characteristics and outcome measurement were scored on a standardized scoring sheet. Due to the wide range in different animals used, ranging from large animal models like pigs to rodents, we decided to limit the study to 168 articles concerning rat models. Within these rat models, we found wide range of baseline animal characteristics, operation techniques, and outcome measurements. Making reliable comparison of results among these studies is impossible. There is a lack of comparability among experimental hernia research, limiting the impact of this experimental research. We therefore propose the establishment of guidelines for experimental hernia research by the EHS.

  16. Steroid-associated osteonecrosis animal model in rats

    Directory of Open Access Journals (Sweden)

    Li-Zhen Zheng

    2018-04-01

    Full Text Available Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s. The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON in rats with pulsed injections of lipopolysaccharide (LPS and methylprednisolone (MPS. Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg and three intraperitoneal injections of MPS (100 mg/kg with a time interval of 24 hour, and then, MPS (40 mg/kg was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19 mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly

  17. Double-observer line transect surveys with Markov-modulated Poisson process models for animal availability.

    Science.gov (United States)

    Borchers, D L; Langrock, R

    2015-12-01

    We develop maximum likelihood methods for line transect surveys in which animals go undetected at distance zero, either because they are stochastically unavailable while within view or because they are missed when they are available. These incorporate a Markov-modulated Poisson process model for animal availability, allowing more clustered availability events than is possible with Poisson availability models. They include a mark-recapture component arising from the independent-observer survey, leading to more accurate estimation of detection probability given availability. We develop models for situations in which (a) multiple detections of the same individual are possible and (b) some or all of the availability process parameters are estimated from the line transect survey itself, rather than from independent data. We investigate estimator performance by simulation, and compare the multiple-detection estimators with estimators that use only initial detections of individuals, and with a single-observer estimator. Simultaneous estimation of detection function parameters and availability model parameters is shown to be feasible from the line transect survey alone with multiple detections and double-observer data but not with single-observer data. Recording multiple detections of individuals improves estimator precision substantially when estimating the availability model parameters from survey data, and we recommend that these data be gathered. We apply the methods to estimate detection probability from a double-observer survey of North Atlantic minke whales, and find that double-observer data greatly improve estimator precision here too. © 2015 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  18. Bioadhesive agents in addition to oral contrast media - evaluation in an animal model

    International Nuclear Information System (INIS)

    Conrad, R.; Schneider, G.; Textor, J.; Schild, H.H.; Fimmers, R.

    1998-01-01

    Purpose: To evaluate the additional effect of bioadhesives in combination with iotrolan and barium as oral contrast media in an animal model. Method: The bioadhesives Noveon, CMC, Tylose and Carbopol 934 were added to iotrolan and barium. The solutions were administered to rabbits by a feeding tube. The animals were investigated by computed tomography (CT) and radiography after 0,5, 4, 12, 24 and in part after 48 hours. Mucosal coating and contrast filling of the bowel were evaluated. Results: Addition of bioadhesives to oral contrast media effected long-term contrast in the small intestine and colon, but no improvement in continuous filling and coating of the gastrointestinal tract was detected. Mucosal coating was seen only in short regions of the caecum and small intestine. In CT the best results for coating were observed with tylose and CMC, in radiography additionally with carbopol and noveon. All contrast medium solutions were well tolerated. Conclusion: The evaluated contrast medium solutions with bioadhesives have shown long-term contrast but no improvement in coating in comparison to conventional oral contrast media. (orig.) [de

  19. A novel animal model of dysphagia following stroke.

    Science.gov (United States)

    Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane

    2014-02-01

    Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

  20. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

    2014-01-01

    To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632

  1. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  2. ANIMAL MODELS OF POST-TRAUMATIC STRESS DISORDER: FACE VALIDITY

    Directory of Open Access Journals (Sweden)

    SONAL eGOSWAMI

    2013-05-01

    Full Text Available Post-traumatic stress disorder (PTSD is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma.

  3. Animal movement constraints improve resource selection inference in the presence of telemetry error

    Science.gov (United States)

    Brost, Brian M.; Hooten, Mevin B.; Hanks, Ephraim M.; Small, Robert J.

    2016-01-01

    Multiple factors complicate the analysis of animal telemetry location data. Recent advancements address issues such as temporal autocorrelation and telemetry measurement error, but additional challenges remain. Difficulties introduced by complicated error structures or barriers to animal movement can weaken inference. We propose an approach for obtaining resource selection inference from animal location data that accounts for complicated error structures, movement constraints, and temporally autocorrelated observations. We specify a model for telemetry data observed with error conditional on unobserved true locations that reflects prior knowledge about constraints in the animal movement process. The observed telemetry data are modeled using a flexible distribution that accommodates extreme errors and complicated error structures. Although constraints to movement are often viewed as a nuisance, we use constraints to simultaneously estimate and account for telemetry error. We apply the model to simulated data, showing that it outperforms common ad hoc approaches used when confronted with measurement error and movement constraints. We then apply our framework to an Argos satellite telemetry data set on harbor seals (Phoca vitulina) in the Gulf of Alaska, a species that is constrained to move within the marine environment and adjacent coastlines.

  4. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Directory of Open Access Journals (Sweden)

    Aya Nakae

    2011-01-01

    Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

  5. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Science.gov (United States)

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

  6. Animal models in fetal medicine and obstetrics

    DEFF Research Database (Denmark)

    Dahl Andersen, Maria; Alstrup, Aage Kristian Olsen; Duvald, Christina Søndergaard

    2018-01-01

    Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and vary regardin...

  7. Animal models got you puzzled?: think pig.

    Science.gov (United States)

    Walters, Eric M; Agca, Yuksel; Ganjam, Venkataseshu; Evans, Tim

    2011-12-01

    Swine are an excellent large animal model for human health and disease because their size and physiology are similar to humans, in particular, with respect to the skin, heart, gastrointestinal tract, and kidneys. In addition, the pig has many emerging technologies that will only enhance the development of the pig as the nonrodent biomedical model of choice. © 2011 New York Academy of Sciences.

  8. ZTI-01 Treatment Improves Survival of Animals Infected with Multidrug Resistant Pseudomonas aeruginosa

    Science.gov (United States)

    Lawrenz, Matthew B; denDekker, Ashley Eb; Cramer, Daniel E; Gabbard, Jon D; Lafoe, Kathryn M; Pfeffer, Tia L; Sotsky, Julie B; Vanover, Carol D; Ellis-Grosse, Evelyn J; Warawa, Jonathan M

    2017-01-01

    Abstract Background ZTI-01 (fosfomycin, FOS, for injection) is currently under US development to treat complicated urinary tract infections. ZTI-01 is unique compared with other antimicrobials in that it inhibits an early step in cell wall synthesis via covalent binding to MurA. ZTI-01 demonstrates broad in vitro activity against Gram-negative (GN) and -positive (GP) bacteria, including multidrug-resistant (MDR) organisms. Our study goals were to determine the efficacy of ZTI-01 as a monotherapy or in combination with meropenem against MDR Pseudomonas aeruginosa in a preclinical model of pulmonary infection. Methods 8 week old neutropenic mice were infected with a MDR strain of P. aeruginosa via intubation-mediated intratracheal (IMIT) instillation. 3 hours after instillation, mice received treatment with ZTI-01, meropenem, or ZTI-01 plus meropenem (combination therapy) q8h for 5 days. Mice were monitored every 8 hours for 7 days for development of disease and moribund animals were humanely euthanized. Lungs and spleens were harvested at euthanasia, or at 7 days for survivors, and processed for bacterial enumeration and development of pathology. Results Mice were challenged with a lethal dose of P. aeruginosa UNC-D. Mock treated animals succumbed to infection within 36 hours post-infection. Animals that received 6 g/kg/day ZTI-01 showed an increase in the MTD (52 hours) and 25% of the cohort were protected from lethal disease. Combining ZTI-01 with meropenem resulted in a significant increase in survival (≥75% of cohorts survived infection). Combination therapy also significantly decreased bacterial numbers in the lungs and inhibited dissemination to the spleens. Furthermore, animals receiving combination therapy were protected from significant inflammation in the lungs and the development of pneumonia. Conclusion Here we report that combination therapy with ZTI-01 and meropenem provides significant improvements in all disease manifestations over treatment with

  9. Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

    Science.gov (United States)

    Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

    2011-01-01

    Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insights on these issues are gained from research using animal models of addiction. In this review, the relationship between brain sites whose learning, memory and executive functions are impaired by chronic drug use and brain sites that are important for effective drug cue extinction learning is explored first. This is followed by an overview of animal research showing improved treatment outcome for drug addiction (e.g. alcohol, amphetamine, cocaine, heroin) when explicit extinction training is conducted in combination with acute dosing of a cognitive-enhancing drug. The mechanism by which cognitive enhancers are thought to exert their benefits is by facilitating consolidation of drug cue extinction memory after activation of glutamatergic receptors. Based on the encouraging work in animals, factors that may be important for the treatment of drug addiction are considered. PMID:21295059

  10. Cardiovascular Changes in Animal Models of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexandre M. Lehnen

    2013-01-01

    Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

  11. Animal model of neuropathic tachycardia syndrome

    Science.gov (United States)

    Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

    2001-01-01

    Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

  12. Improving the Translation of Animal Ischemic Stroke Studies to Humans

    OpenAIRE

    Jickling, Glen C; Sharp, Frank R

    2014-01-01

    Despite testing more than 1026 therapeutic strategies in models ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendation...

  13. Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research

    DEFF Research Database (Denmark)

    Denton, Paul W.; Søgaard, Ole Schmeltz; Tolstrup, Martin

    2016-01-01

    Research challenges associated with understanding HIV persistence during antiretroviral therapy can be categorized as temporal, spatial and combinatorial. Temporal research challenges relate to the timing of events during establishment and maintenance of HIV persistence. Spatial research challeng...... for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence....... will improve our understanding of HIV persistence and move the field closer to achieving eradication of persistent HIV. Given that humanized mice and non-human primate HIV models permit rigorous control of experimental conditions, these models have been used extensively as in vivo research platforms...

  14. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

  15. Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

    NARCIS (Netherlands)

    Brouwer, E.; Huitema, M. G.; Klok, P. A.; de Weerd, H.; Tervaert, J. W.; Weening, J. J.; Kallenberg, C. G.

    1993-01-01

    To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

  16. ANTIMYELOPEROXIDASE-ASSOCIATED PROLIFERATIVE GLOMERULONEPHRITIS - AN ANIMAL-MODEL

    NARCIS (Netherlands)

    BROUWER, E; HUITEMA, MG; KLOK, PA; DEWEERD, H; TERVAERT, JWC; WEENING, JJ; KALLENBERG, CGM

    1993-01-01

    To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,

  17. Animal model of human disease. Multiple myeloma

    NARCIS (Netherlands)

    Radl, J.; Croese, J.W.; Zurcher, C.; Enden-Vieveen, M.H.M. van den; Leeuw, A.M. de

    1988-01-01

    Animal models of spontaneous and induced plasmacytomas in some inbred strains of mice have proven to be useful tools for different studies on tumorigenesis and immunoregulation. Their wide applicability and the fact that after their intravenous transplantation, the recipient mice developed bone

  18. Mathematical modeling and simulation in animal health. Part I: Moving beyond pharmacokinetics.

    Science.gov (United States)

    Riviere, J E; Gabrielsson, J; Fink, M; Mochel, J

    2016-06-01

    The application of mathematical modeling to problems in animal health has a rich history in the form of pharmacokinetic modeling applied to problems in veterinary medicine. Advances in modeling and simulation beyond pharmacokinetics have the potential to streamline and speed-up drug research and development programs. To foster these goals, a series of manuscripts will be published with the following goals: (i) expand the application of modeling and simulation to issues in veterinary pharmacology; (ii) bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; (iii) explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, vast weight ranges among adults within a single species, interspecies differences, small animal species research where data collection is limited to sparse sampling, availability of different sampling matrices); and (iv) describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. This study introduces these concepts and introduces new approaches to modeling and simulation as well as clearly articulate basic assumptions and good practices. The driving force behind these activities is to create predictive models that are based on solid physiological and pharmacological principles as well as adhering to the limitations that are fundamental to applying mathematical and statistical models to biological systems. © 2015 John Wiley & Sons Ltd.

  19. Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

    Science.gov (United States)

    de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

    2012-12-01

    The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

  20. Research advances in animal models of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    HUANG Haiyan

    2014-09-01

    Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.

  1. Current Animal Models of Postoperative Spine Infection and Potential Future Advances

    Directory of Open Access Journals (Sweden)

    Alexandra eStavrakis

    2015-05-01

    Full Text Available Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions.

  2. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  3. Geospatial forecast model for tsetse-transmitted animal ...

    African Journals Online (AJOL)

    Results indicate that GIS model developed for parasitic diseases based on growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. GIS for animal trypanosomosis was created using Food and Agriculture Organization – Crop Production System Zones (FAO-CPSZ) database and Normalized ...

  4. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

  5. Small Animal [18F]FDG PET Imaging for Tumor Model Study

    International Nuclear Information System (INIS)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

    2008-01-01

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

  6. A proposed model for the transfer of environmental tritium to man and tritium metabolism in model animals

    International Nuclear Information System (INIS)

    Saito, Masahiro; Ishida, M.R.

    1987-01-01

    To evaluate the accumulated dose in human bodies due to the environmental tritium, it is of required to establish an adequate model for the tritium transfer from the environment to man and to obtain enough information on the metabolic behaviour of tritium in animal bodies using model animal system. In this report, first we describe about a proposed model for the transfer of environmental tritium to man and secondly mention briefly about the recent works on the tritium metabolism in newborn animals which have been treated as a model system of tritium intake through food chain. (author)

  7. Translational neuropharmacology and the appropriate and effective use of animal models.

    Science.gov (United States)

    Green, A R; Gabrielsson, J; Fone, K C F

    2011-10-01

    This issue of the British Journal of Pharmacology is dedicated to reviews of the major animal models used in neuropharmacology to examine drugs for both neurological and psychiatric conditions. Almost all major conditions are reviewed. In general, regulatory authorities require evidence for the efficacy of novel compounds in appropriate animal models. However, the failure of many compounds in clinical trials following clear demonstration of efficacy in animal models has called into question both the value of the models and the discovery process in general. These matters are expertly reviewed in this issue and proposals for better models outlined. In this editorial, we further suggest that more attention be made to incorporate pharmacokinetic knowledge into the studies (quantitative pharmacology). We also suggest that more attention be made to ensure that full methodological details are published and recommend that journals should be more amenable to publishing negative data. Finally, we propose that new approaches must be used in drug discovery so that preclinical studies become more reflective of the clinical situation, and studies using animal models mimic the anticipated design of studies to be performed in humans, as closely as possible. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  8. Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

    Science.gov (United States)

    Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

    2016-01-01

    Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Mathematical modeling and simulation in animal health - Part II: principles, methods, applications, and value of physiologically based pharmacokinetic modeling in veterinary medicine and food safety assessment.

    Science.gov (United States)

    Lin, Z; Gehring, R; Mochel, J P; Lavé, T; Riviere, J E

    2016-10-01

    This review provides a tutorial for individuals interested in quantitative veterinary pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in veterinary medicine. This is important as the application of PBPK modeling in veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food-producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food-producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed-effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in veterinary pharmacology and toxicology. © 2016 John Wiley & Sons Ltd.

  10. Architecture optimization at IPEN animal facility in order to improve the welfare and the quality of the animals employed at radiopharmaceutical tests

    Energy Technology Data Exchange (ETDEWEB)

    Lainetti, Elizabeth Brigagao de Faria; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: eblainet@ipen.br; Passos, Luiz Augusto Correa [Universidade Estadual de Campinas, SP (Brazil). Centro Multidisciplinar para a Investigacao Biologica (CEMIB/UNICAMP)

    2009-07-01

    The production and the issue of high quality laboratory animals are essentials for the accomplishment of vanguard scientific research, with reproducibility and universality. The quality of those animals depends, largely, of the available facilities for their production and lodging, to assure the demanded sanitary control and animals' well being, in agreement with the ethical principles that control the activity. The facilities also have to fill out other requirements, such as: the functionality of the environments to make possible the suitable and efficient handling of the animals, facilitating the execution of the routine activities; the respect to ergonomic principles to provide a safe environment and the operators' well being. The facilities design is of vital importance so that the mentioned requirements can be reached. The project of the Nuclear and Energy Research Institute (IPEN) Animal House Facilities was accomplished in the year of 1964. However, by that time there were not the current recommendations with respect to the sanitary, genetic and environmental controls. The facility was planned with the objective of being a production unit and a local for keeping of defined animals from sanitary, genetic and environmental point of view. Nevertheless, the original unit drawing presents an unsuitable distribution of the area where animals are stockpiled and different activities are performed. The Animal House Facilities occupies an area of 840 m{sup 2}, with one pavement, where the production areas and the stock of original animal models of the own institution are distributed, as well as the maintenance of animals from other national or foreigner institutions. It supplies rats and mice for biological tests of radiopharmaceutical lots, produced in IPEN, before they be sent to hospitals and clinics spread out in Brazil, for use in Nuclear Medicine. It also supplies rats and mice for tests of odontologic materials, for tests with growth hormones and for

  11. Architecture optimization at IPEN animal facility in order to improve the welfare and the quality of the animals employed at radiopharmaceutical tests

    International Nuclear Information System (INIS)

    Lainetti, Elizabeth Brigagao de Faria; Nascimento, Nanci do; Passos, Luiz Augusto Correa

    2009-01-01

    The production and the issue of high quality laboratory animals are essentials for the accomplishment of vanguard scientific research, with reproducibility and universality. The quality of those animals depends, largely, of the available facilities for their production and lodging, to assure the demanded sanitary control and animals' well being, in agreement with the ethical principles that control the activity. The facilities also have to fill out other requirements, such as: the functionality of the environments to make possible the suitable and efficient handling of the animals, facilitating the execution of the routine activities; the respect to ergonomic principles to provide a safe environment and the operators' well being. The facilities design is of vital importance so that the mentioned requirements can be reached. The project of the Nuclear and Energy Research Institute (IPEN) Animal House Facilities was accomplished in the year of 1964. However, by that time there were not the current recommendations with respect to the sanitary, genetic and environmental controls. The facility was planned with the objective of being a production unit and a local for keeping of defined animals from sanitary, genetic and environmental point of view. Nevertheless, the original unit drawing presents an unsuitable distribution of the area where animals are stockpiled and different activities are performed. The Animal House Facilities occupies an area of 840 m 2 , with one pavement, where the production areas and the stock of original animal models of the own institution are distributed, as well as the maintenance of animals from other national or foreigner institutions. It supplies rats and mice for biological tests of radiopharmaceutical lots, produced in IPEN, before they be sent to hospitals and clinics spread out in Brazil, for use in Nuclear Medicine. It also supplies rats and mice for tests of odontologic materials, for tests with growth hormones and for researches of

  12. Continuity of Business Plans for Animal Disease Outbreaks: Using a Logic Model Approach to Protect Animal Health, Public Health, and Our Food Supply

    Directory of Open Access Journals (Sweden)

    Heather Allen

    2013-04-01

    Full Text Available Foreign animal diseases can have a devastating impact on the American economy and agriculture system, while significantly disrupting the food supply chain, and affecting animal health and public health. Continuity of business during an animal disease outbreak aims to mitigate these agriculture-related losses by facilitating normal business operations through the managed movement of non-infected animals and non-contaminated animal products. During a foreign animal disease outbreak, there are competing objectives of trying to control and contain the outbreak while allowing non-infected premises to continue normal business operations to the greatest extent possible. Using a logic model approach, this article discusses the importance of continuity of business planning during an animal disease outbreak, providing a detailed and transparent theoretical framework for continuity of business planning for animal agriculture stakeholders. The logic model provides a basis for continuity of business planning, which is rapidly gaining focus and interest in the animal emergency management community. This unique logic model offers a framework for effective planning and subsequent evaluation of continuity of business plans and processes, by identifying explicit stakeholders, inputs, and activities, alongside the desired outputs and outcomes of such planning.

  13. A method of shadow puppet figure modeling and animation

    Institute of Scientific and Technical Information of China (English)

    Xiao-fang HUANG; Shou-qian SUN; Ke-jun ZHANG; Tian-ning XU; Jian-feng WU; Bin ZHU

    2015-01-01

    To promote the development of the intangible cultural heritage of the world, shadow play, many studies have focused on shadow puppet modeling and interaction. Most of the shadow puppet figures are still imaginary, spread by ancients, or carved and painted by shadow puppet artists, without consideration of real dimensions or the appearance of human bodies. This study proposes an algorithm to transform 3D human models to 2D puppet figures for shadow puppets, including automatic location of feature points, automatic segmentation of 3D models, automatic extraction of 2D contours, automatic clothes matching, and animation. Experiment proves that more realistic and attractive figures and animations of the shadow puppet can be generated in real time with this algorithm.

  14. The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

    Science.gov (United States)

    Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...

  15. Inverse modeling and animation of growing single-stemmed trees at interactive rates

    Science.gov (United States)

    S. Rudnick; L. Linsen; E.G. McPherson

    2007-01-01

    For city planning purposes, animations of growing trees of several species can be used to deduce which species may best fit a particular environment. The models used for the animation must conform to real measured data. We present an approach for inverse modeling to fit global growth parameters. The model comprises local production rules, which are iteratively and...

  16. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

    Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

  17. 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.

  18. Spontaneous appearance of Tay-Sachs disease in an animal model.

    Science.gov (United States)

    Zeng, B J; Torres, P A; Viner, T C; Wang, Z H; Raghavan, S S; Alroy, J; Pastores, G M; Kolodny, E H

    2008-01-01

    Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of beta-hexosaminidase A (Hex A). Deficiency of Hex A in TSD is caused by a defect of the alpha-subunit resulting from mutations of the HEXA gene. To date, there is no effective treatment for TSD. Animal models of genetic diseases, similar to those known to exist in humans, are valuable and essential research tools for the study of potentially effective therapies. However, there is no ideal animal model of TSD available for use in therapeutic trials. In the present study, we report an animal model (American flamingo; Phoenicopterus ruber) of TSD with Hex A deficiency occurring spontaneously in nature, with accumulation of G(M2)-ganglioside, deficiency of Hex A enzymatic activity, and a homozygous P469L mutation in exon 12 of the hexa gene. In addition, we have isolated the full-length cDNA sequence of the flamingo, which consists of 1581 nucleotides encoding a protein of 527 amino acids. Its coding sequence indicates approximately 71% identity at the nucleotide level and about 72.5% identity at the amino acid level with the encoding region of the human HEXA gene. This animal model, with many of the same features as TSD in humans, could represent a valuable resource for investigating therapy of TSD.

  19. Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

    Directory of Open Access Journals (Sweden)

    Eduardo Schiffrin

    2013-09-01

    Full Text Available Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo, and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

  20. Institutional transparency improves public perception of lab animal technicians and support for animal research.

    Science.gov (United States)

    Mills, Katelyn E; Han, Zetta; Robbins, Jesse; Weary, Daniel M

    2018-01-01

    The use of animals in research is controversial and often takes place under a veil of secrecy. Lab animal technicians responsible for the care of animals at research institutions are sometimes described as performing 'dirty work' (i.e. professions that are viewed as morally tainted), and may be stigmatized by negative perceptions of their job. This study assessed if transparency affects public perceptions of lab animal technicians and support for animal research. Participants (n = 550) were randomly assigned to one of six scenarios (using a 3x2 design) that described identical research varying only the transparency of the facility (low, high) and the species used (mice, dogs, cows). Participants provided Likert-type and open-ended responses to questions about the personal characteristics (warmth, competence) of a hypothetical lab technician 'Cathy' and their support for the described research. Quantitative analysis showed participants in the low-transparency condition perceived Cathy to be less warm and were less supportive of the research regardless of animal species. Qualitative responses varied greatly, with some participants expressing support for both Cathy and the research. These results suggest that increasing transparency in lab animal institutions could result in a more positive perception of lab animal researchers and the work that they do.

  1. Understanding animal fears: a comparison of the cognitive vulnerability and harm-looming models

    Directory of Open Access Journals (Sweden)

    Armfield Jason M

    2007-12-01

    Full Text Available Abstract Background The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fear.

  2. Animal behavior models of the mechanisms underlying antipsychotic atypicality.

    NARCIS (Netherlands)

    Geyer, M.A.; Ellenbroek, B.A.

    2003-01-01

    This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

  3. Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model.

    Science.gov (United States)

    Santos, Camila Mauricio; Peres, Fernanda Fiel; Diana, Mariana Cepollaro; Justi, Veronica; Suiama, Mayra Akimi; Santana, Marcela Gonçalves; Abílio, Vanessa Costhek

    2016-10-01

    Schizophrenia is a highly disabling mental disorder, in which genetics and environmental factors interact culminating in the disease. The treatment of negative symptoms and cognitive deficits with antipsychotics is currently inefficient and is an important field of research. Environmental enrichment (EE) has been suggested to improve some cognitive deficits in animal models of various psychiatric disorders. In this study, we aimed to evaluate a possible beneficial effect of early and long-term exposure to EE on an animal model of schizophrenia, the SHR strain. Young male Wistar rats (control strain) and SHRs (21 post-natal days) were housed for 6weeks in two different conditions: in large cages (10 animals per cage) containing objects of different textures, forms, colors and materials that were changed 3 times/week (EE condition) or in standard cages (5 animals per cage - Control condition). Behavioral evaluations - social interaction (SI), locomotion, prepulse inhibition of startle (PPI) and spontaneous alternation (SA) - were performed 6weeks after the end of EE. SHRs presented deficits in PPI (a sensorimotor impairment), SI (mimicking the negative symptoms) and SA (a working memory deficit), and also hyperlocomotion (modeling the positive symptoms). EE was able to reduce locomotion and increase PPI in both strains, and to prevent the working memory deficit in SHRs. EE also increased the number of neurons in the CA1 and CA3 of the hippocampus. In conclusion, EE can be a potential nonpharmacological strategy to prevent some behavioral deficits associated with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study.

    Science.gov (United States)

    Aide, Nicolas; Louis, Marie-Hélène; Dutoit, Soizic; Labiche, Alexandre; Lemoisson, Edwige; Briand, Mélanie; Nataf, Valérie; Poulain, Laurent; Gauduchon, Pascal; Talbot, Jean-Noël; Montravers, Françoise

    2007-10-01

    To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.

  5. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

    Science.gov (United States)

    Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

    2008-12-01

    Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

  6. Does the Animal Fun program improve social-emotional and behavioural outcomes in children aged 4-6 years?

    Science.gov (United States)

    Piek, Jan P; Kane, Robert; Rigoli, Daniela; McLaren, Sue; Roberts, Clare M; Rooney, Rosanna; Jensen, Lynn; Dender, Alma; Packer, Tanya; Straker, Leon

    2015-10-01

    Animal Fun was designed to enhance motor and social development in young children. Its efficacy in improving motor skills was presented previously using a randomised controlled trial and a multivariate nested cohort design. Based on the Environmental Stress Hypothesis, it was argued that the program would also result in positive mental health outcomes, investigated in the current study. Pre-intervention scores were recorded for 511 children aged 4.83-6.17 years (M=5.42, SD=.30). Intervention and control groups were compared 6 months following intervention, and again in their first school year. Changes in teacher-rated prosocial behaviour and total difficulties were assessed using the Strengths and Difficulties Questionnaire, and data analysed using Generalised Linear Mixed Models. There was a significant improvement in prosocial behaviour of children in the intervention group six months after initial testing, which remained at 18-month follow-up. Total difficulties decreased at 6 months for the intervention group, with no change at 18 months. This effect was present only for the hyperactivity/inattention subscale. The only significant change for the control group was an increase in hyperactivity/inattention scores from pre-intervention to 18-month follow-up. The Animal Fun program appears to be effective in improving social and behavioural outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Improved instrumentation for blood flow velocity measurements in the microcirculation of small animals

    International Nuclear Information System (INIS)

    Mesquita, Jayme Alves Jr. de; Bouskela, Eliete; Wajnberg, Eliane; Lopes de Melo, Pedro

    2007-01-01

    Microcirculation is the generic name of vessels with internal diameter less than 100 μm of the circulatory system, whose main functions are tissue nutrition and oxygen supply. In microcirculatory studies, it is important to know the amount of oxyhemoglobin present in the blood and how fast it is moving. The present work describes improvements introduced in a classical hardware-based instrument that has usually been used to monitor blood flow velocity in the microcirculation of small animals. It consists of a virtual instrument that can be easily incorporated into existing hardware-based systems, contributing to reduce operator related biases and allowing digital processing and storage. The design and calibration of the modified instrument are described as well as in vitro and in vivo results obtained with electrical models and small animals, respectively. Results obtained in in vivo studies showed that this new system is able to detect a small reduction in blood flow velocity comparing arteries and arterioles (p<0.002) and a further reduction in capillaries (p<0.0001). A significant increase in velocity comparing capillaries and venules (p<0.001) and venules and veins (p<0.001) was also observed. These results are in close agreement with biophysical principles. Moreover, the improvements introduced in the device allowed us to clearly observe changes in blood flow introduced by a pharmacological intervention, suggesting that the system has enough temporal resolution to track these microcirculatory events. These results were also in close conformity to physiology, confirming the high scientific potential of the modified system and indicating that this instrument can also be useful for pharmacological evaluations

  8. An improved data base for the description of dairy cows in the German agricultural emission model GAS-EM

    DEFF Research Database (Denmark)

    Dämmgen, Ulrich; Haenel, Hans-Dieter; Rösemann, Claus

    2010-01-01

    The application of the previously published detailed model describing dairy cow husbandry in the German agricultural emission model requires an extended and improved data base. This concerns animal weights, weight gains, regional feed regimes, feeding requirements and feed properties as well...... of animal performance. The knowledge of hitherto unpublished data allows for a recalculation and revaluation of nitrogen excretions and ammonia emission factors....

  9. Animal-Computer Interaction: Animal-Centred, Participatory, and Playful Design

    NARCIS (Netherlands)

    Pons, Patricia; Hirskyj-Douglas, Ilyena; Nijholt, Antinus; Cheok, Adrian D.; Spink, Andrew; Riedel, Gernot; Zhou, Liting; Teekens, Lisanne; Albatal, Rami; Gurrin, Cathal

    In recent years there has been growing interest in developing technology to improve animal's wellbeing and to support the interaction of animals within the digital world. The field of Animal-Computer Interaction (ACI) considers animals as the end-users of the technology being developed, orienting

  10. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    1Research in Biological Sciences - NUPEB, 2Department of Foods, School of Nutrition, Ouro Preto University, ..... ical (large) doses of drug required, (2) the requirement for .... Animal models can lead to understanding of the interactions.

  11. An improved method for lifting and transporting anesthetized pigs within an animal facility

    DEFF Research Database (Denmark)

    Schumacher-Petersen, Camilla; Hammelev, Karsten Pharao; Flescher, Jens Erik

    2014-01-01

    Transporting anesthetized pigs in a laboratory setting often requires strenuous manual lifting, posing a hazard to the safety of animal care personnel and to the welfare of the pigs. The authors developed an improved approach to lifting and transporting anesthetized pigs weighing up to 350 kg using...... mechanical lifts. Different equipment was used to accommodate pigs of different sizes as well as the building designs of three animal facilities. Using the lifts, anesthetized pigs are carried on sheets to maintain their comfort while being transported. The approach refines previous methods for handling...

  12. Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Caballero, Miguel; Núñez, Fabiana; Ahern, Siobhán; Cuffí, Maria L; Carbonell, Lourdes; Sánchez, Silvia; Fernández-Dueñas, Víctor; Ciruela, Francisco

    2011-04-20

    Nowadays the pharmacological treatment of the attention deficit hyperactivity disorder (ADHD) is based on amphetamine derivatives (i.e. methylphenidate). However, these drugs induce a large array of adverse side effects, thus less aggressive psychostimulant drugs (i.e. caffeine) are being proposed in the management of ADHD. Following this tendency, we decided to study the possible therapeutic use of caffeine in an animal model of ADHD, namely the neonatal 6-hydroxy-dopamine (6-OHDA)-lesioned rat. Therefore, at postnatal day 7 rats were lesioned at the left striatum with 6-OHDA or with saline. Thereafter, at postnatal day 25 their activity and attention were measured with the Olton maze before caffeine was administered ad libitum in the drinking water. Next, after 14 days of caffeine treatment, we repeated these measurements to assess the effect of caffeine on motor activity and attention deficit. Interestingly, while no changes in the motor activity measurements were observed before and after caffeine administration, a significant improvement in the attention deficit of the 6-OHDA lesioned rats was achieved after caffeine treatment. Thus, our results led us to hypothesize that caffeine might be useful to manage the attention deficit during the prepubertal period of ADHD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  14. Review: Animal model and the current understanding of molecule dynamics of adipogenesis.

    Science.gov (United States)

    Campos, C F; Duarte, M S; Guimarães, S E F; Verardo, L L; Wei, S; Du, M; Jiang, Z; Bergen, W G; Hausman, G J; Fernyhough-Culver, M; Albrecht, E; Dodson, M V

    2016-06-01

    Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.

  15. Model systems to study immunomodulation in domestic food animals.

    Science.gov (United States)

    Roth, J A; Flaming, K P

    1990-01-01

    Development of immunomodulators for use in food producing animals is an active area of research. This research has generally incorporated aspects of immunosuppression in model systems. This methodology is appropriate because most of the research has been aimed at developing immunomodulators for certain economically significant diseases in which immunosuppression is believed to be an important component of their pathogenesis. The primary focus has been on stress-associated diseases (especially bovine respiratory disease), infectious diseases in young animals, and mastitis. The model systems used have limitations, but they have demonstrated that immunomodulators are capable of significantly increasing resistance to these important infectious disease syndromes. As our understanding of molecular immunology increases and as more potential immunomodulators become available, the use of relevant model systems should greatly aid advancement in the field of immunomodulation.

  16. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  17. Overview on available animal models for application in leukemia research

    International Nuclear Information System (INIS)

    Borkhardt, A.; Sanchez-Garcia, I.; Cobaleda, C.; Hauer, J.

    2015-01-01

    The term ''leukemia'' encompasses a group of diseases with a variable clinical and pathological presentation. Its cellular origin, its biology and the underlying molecular genetic alterations determine the very variable and individual disease phenotype. The focus of this review is to discuss the most important guidelines to be taken into account when we aim at developing an ''ideal'' animal model to study leukemia. The animal model should mimic all the clinical, histological and molecular genetic characteristics of the human phenotype and should be applicable as a clinically predictive model. It should achieve all the requirements to be used as a standardized model adaptive to basic research as well as to pharmaceutical practice. Furthermore it should fulfill all the criteria to investigate environmental risk factors, the role of genomic mutations and be applicable for therapeutic testing. These constraints limit the usefulness of some existing animal models, which are however very valuable for basic research. Hence in this review we will primarily focus on genetically engineered mouse models (GEMMs) to study the most frequent types of childhood leukemia. GEMMs are robust models with relatively low site specific variability and which can, with the help of the latest gene modulating tools be adapted to individual clinical and research questions. Moreover they offer the possibility to restrict oncogene expression to a defined target population and regulate its expression level as well as its timely activity. Until recently it was only possible in individual cases to develop a murin model, which fulfills the above mentioned requirements. Hence the development of new regulatory elements to control targeted oncogene expression should be priority. Tightly controlled and cell specific oncogene expression can then be combined with a knock-in approach and will depict a robust murine model, which enables almost physiologic oncogene

  18. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.

    Science.gov (United States)

    Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell'Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

    2008-03-01

    We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.

  19. Active Compounds of Rhubarb Root and Rhizome in Animal Model Experiments of Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ai-ju Liu

    2015-01-01

    Full Text Available Rhubarb root and rhizome (RRR has been clinically used for stroke at least 2000 years and is still used in modern times in both China and elsewhere worldwide. The objective of present study was to evaluate the efficacy of active compounds of RRR (ACRRR for experimental ischemic stroke. Studies of ACRRR in animal models of ischemic stroke were identified from 5 databases until April 2014. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit score and infarct size. All the data were analyzed using RevMan 5.1 software. As a result, 20 studies were identified describing procedures involving 577 animals. The quality score of studies ranges from 2 to 6, and the median was 3.4. Six studies showed significant effects of ACRRR for improving infarct size compared with model group (P<0.01. Six studies indicated significant effects of ACRRR for improving the neurological deficit scores according to Zea longa criterion or eight-point criterion (P<0.01. In conclusion, these findings demonstrated a possible efficacy of ACRRR that have potential neuroprotective effect for experimental ischemic stroke. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

  20. An animal model to study regenerative endodontics.

    Science.gov (United States)

    Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh

    2011-02-01

    A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright © 2011. Published by Elsevier Inc.

  1. Review A balanced perspective on animal welfare for improved ...

    African Journals Online (AJOL)

    Chulayo, Amanda

    2015-12-01

    Dec 1, 2015 ... Increased public concern for animal welfare in the logistics chain has .... still complain about poor management of animals and state that ... assurance of good animal welfare and healthier foods to all participating supply chains, animal genetics has ...... Toward a global perspective on farm animal welfare.

  2. Monkeypox disease transmission in an experimental setting: prairie dog animal model.

    Directory of Open Access Journals (Sweden)

    Christina L Hutson

    Full Text Available Monkeypox virus (MPXV is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox. MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively. Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission.

  3. Food allergy: What do we learn from animal models?

    NARCIS (Netherlands)

    Knippels, L.M.J.; Wijk, F. van; Penninks, A.H.

    2004-01-01

    Purpose of review This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. Recent findings

  4. Parathyroid diseases and animal models.

    Science.gov (United States)

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

    CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

  5. Animal models for studying female genital tract infection with Chlamydia trachomatis.

    Science.gov (United States)

    De Clercq, Evelien; Kalmar, Isabelle; Vanrompay, Daisy

    2013-09-01

    Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model.

  6. Strategies and facilities in order to improve animal welfare Estratégias e instalações para melhorar o bem-estar animal

    Directory of Open Access Journals (Sweden)

    Daniella Jorge de Moura

    2010-07-01

    Full Text Available To keep the position in being a world-wide exporter of chicken meat, Brazil must meet international quality standards, always seeking alternative resources of improvement, without increasing production costs, including litter quality, requirements of animal welfare and environment affairs, such as the use and reuse of broiler litter. Researches are performed in the areas of animal welfare, environment, animal behavior and use of modern climatization technology improving the quality of the environment created to raise broilers, also trying to reduce the greenhouse gas emissions and global warming in the environment, becoming a sustainable production system. This paper has a bibliographic revision of the subject mentioned above, intending to show a state-of-art key factors related to a new concept of broiler environment and welfare.Para manter a posição de maior exportador de carne de frango, o Brasil deve se adequar às exigências internacionais dos padrões de qualidade, procurando sempre recursos alternativos de melhoria, sem grande incremento no custo de produção, incluindo a qualidade da cama, requisitos de bem-estar animal e as questões ambientais, como o uso e a reutilização das camas de frango. Para isso são necessárias pesquisas nas áreas de bem-estar animal, ambiência, comportamento animal e uso de tecnologias de climatização modernas que aperfeiçoem a qualidade do ambiente gerado para criação dos frangos, visando, além deste fator, menor emissão de gases com potencial efeito estufa para o ambiente, tornando-se um sistema de produção sustentável. De acordo com o exposto, realizou-se uma ampla revisão bibliográfica deste assunto, buscando mostrar o estado da arte dos principais fatores relacionados aos novos conceitos de ambiência e bem-estar de frangos de corte.

  7. Fundamental Moral Attitudes to Animals and Their Role in Judgment: An Empirical Model to Describe Fundamental Moral Attitudes to Animals and Their Role in Judgment on the Culling of Healthy Animals During an Animal Disease Epidemic

    NARCIS (Netherlands)

    Cohen, N.E.; Brom, F.W.A.; Stassen, E.N.

    2009-01-01

    In this paper, we present and defend the theoretical framework of an empirical model to describe people’s fundamental moral attitudes (FMAs) to animals, the stratification of FMAs in society and the role of FMAs in judgment on the culling of healthy animals in an animal disease epidemic. We used

  8. Immune-mediated animal models of Tourette syndrome

    Science.gov (United States)

    Hornig, Mady; Lipkin, W. Ian

    2014-01-01

    An autoimmune diathesis has been proposed in Tourette syndrome (TS) and related neuropsychiatric disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism and anorexia nervosa. Environmental triggers including infection and xenobiotics are hypothesized to lead to the production of brain-directed autoantibodies in a subset of genetically susceptible individuals. Although much work has focused on Group A Streptococcus (GAS), the role of this common childhood infection remains controversial. Animal model studies based on immune and autoantibody findings in TS have demonstrated immunoglobulin (Ig) deposits and stereotypic movements and related behavioral disturbances reminiscent of TS following exposure to GAS and other activators of host anti-microbial responses, soluble immune mediators and anti-GAS or anti-neuronal antibodies. Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome. PMID:23313649

  9. A review of simulation modelling approaches used for the spread of zoonotic influenza viruses in animal and human populations.

    Science.gov (United States)

    Dorjee, S; Poljak, Z; Revie, C W; Bridgland, J; McNab, B; Leger, E; Sanchez, J

    2013-09-01

    Increasing incidences of emerging and re-emerging diseases that are mostly zoonotic (e.g. severe acute respiratory syndrome, avian influenza H5N1, pandemic influenza) has led to the need for a multidisciplinary approach to tackling these threats to public and animal health. Accordingly, a global movement of 'One-Health/One-Medicine' has been launched to foster collaborative efforts amongst animal and human health officials and researchers to address these problems. Historical evidence points to the fact that pandemics caused by influenza A viruses remain a major zoonotic threat to mankind. Recently, a range of mathematical and computer simulation modelling methods and tools have increasingly been applied to improve our understanding of disease transmission dynamics, contingency planning and to support policy decisions on disease outbreak management. This review provides an overview of methods, approaches and software used for modelling the spread of zoonotic influenza viruses in animals and humans, particularly those related to the animal-human interface. Modelling parameters used in these studies are summarized to provide references for future work. This review highlights the limited application of modelling research to influenza in animals and at the animal-human interface, in marked contrast to the large volume of its research in human populations. Although swine are widely recognized as a potential host for generating novel influenza viruses, and that some of these viruses, including pandemic influenza A/H1N1 2009, have been shown to be readily transmissible between humans and swine, only one study was found related to the modelling of influenza spread at the swine-human interface. Significant gaps in the knowledge of frequency of novel viral strains evolution in pigs, farm-level natural history of influenza infection, incidences of influenza transmission between farms and between swine and humans are clearly evident. Therefore, there is a need to direct

  10. 3D animation model with augmented reality for natural science learning in elementary school

    Science.gov (United States)

    Hendajani, F.; Hakim, A.; Lusita, M. D.; Saputra, G. E.; Ramadhana, A. P.

    2018-05-01

    Many opinions from primary school students' on Natural Science are a difficult lesson. Many subjects are not easily understood by students, especially on materials that teach some theories about natural processes. Such as rain process, condensation and many other processes. The difficulty that students experience in understanding it is that students cannot imagine the things that have been taught in the material. Although there is material to practice some theories but is actually quite limited. There is also a video or simulation material in the form of 2D animated images. Understanding concepts in natural science lessons are also poorly understood by students. Natural Science learning media uses 3-dimensional animation models (3D) with augmented reality technology, which offers some visualization of science lessons. This application was created to visualize a process in Natural Science subject matter. The hope of making this application is to improve student's concept. This app is made to run on a personal computer that comes with a webcam with augmented reality. The app will display a 3D animation if the camera can recognize the marker.

  11. How animals move along? Exactly solvable model of superdiffusive spread resulting from animal's decision making.

    Science.gov (United States)

    Tilles, Paulo F C; Petrovskii, Sergei V

    2016-07-01

    Patterns of individual animal movement have been a focus of considerable attention recently. Of particular interest is a question how different macroscopic properties of animal dispersal result from the stochastic processes occurring on the microscale of the individual behavior. In this paper, we perform a comprehensive analytical study of a model where the animal changes the movement velocity as a result of its behavioral response to environmental stochasticity. The stochasticity is assumed to manifest itself through certain signals, and the animal modifies its velocity as a response to the signals. We consider two different cases, i.e. where the change in the velocity is or is not correlated to its current value. We show that in both cases the early, transient stage of the animal movement is super-diffusive, i.e. ballistic. The large-time asymptotic behavior appears to be diffusive in the uncorrelated case but super-ballistic in the correlated case. We also calculate analytically the dispersal kernel of the movement and show that, whilst it converge to a normal distribution in the large-time limit, it possesses a fatter tail during the transient stage, i.e. at early and intermediate time. Since the transients are known to be highly relevant in ecology, our findings may indicate that the fat tails and superdiffusive spread that are sometimes observed in the movement data may be a feature of the transitional dynamics rather than an inherent property of the animal movement.

  12. Towards an ethological animal model of depression? A study on horses.

    Directory of Open Access Journals (Sweden)

    Carole Fureix

    Full Text Available Recent reviews question current animal models of depression and emphasise the need for ethological models of mood disorders based on animals living under natural conditions. Domestic horses encounter chronic stress, including potential stress at work, which can induce behavioural disorders (e.g. "apathy". Our pioneering study evaluated the potential of domestic horses in their usual environment to become an ethological model of depression by testing this models' face validity (i.e. behavioural similarity with descriptions of human depressive states.We observed the spontaneous behaviour of 59 working horses in their home environment, focusing on immobility bouts of apparent unresponsiveness when horses displayed an atypical posture (termed withdrawn hereafter, evaluated their responsiveness to their environment and their anxiety levels, and analysed cortisol levels. Twenty-four percent of the horses presented the withdrawn posture, also characterized by gaze, head and ears fixity, a profile that suggests a spontaneous expression of "behavioural despair". When compared with control "non-withdrawn" horses from the same stable, withdrawn horses appeared more indifferent to environmental stimuli in their home environment but reacted more emotionally in more challenging situations. They exhibited lower plasma cortisol levels. Withdrawn horses all belonged to the same breed and females were over-represented.Horse might be a useful potential candidate for an animal model of depression. Face validity of this model appeared good, and potential genetic input and high prevalence of these disorders in females add to the convergence. At a time when current animal models of depression are questioned and the need for novel models is expressed, this study suggests that novel models and biomarkers could emerge from ethological approaches in home environments.

  13. Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

    Science.gov (United States)

    Holfeld, Johannes; Zimpfer, Daniel; Albrecht-Schgoer, Karin; Stojadinovic, Alexander; Paulus, Patrick; Dumfarth, Julia; Thomas, Anita; Lobenwein, Daniela; Tepeköylü, Can; Rosenhek, Raphael; Schaden, Wolfgang; Kirchmair, Rudolf; Aharinejad, Seyedhossein; Grimm, Michael

    2016-12-01

    Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm 2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Understanding in vivo modelling of depression in non-human animals: a systematic review protocol

    DEFF Research Database (Denmark)

    Bannach-Brown, Alexandra; Liao, Jing; Wegener, Gregers

    2016-01-01

    experimental model(s) to induce or mimic a depressive-like phenotype. Data that will be extracted include the model or method of induction; species and gender of the animals used; the behavioural, anatomical, electrophysiological, neurochemical or genetic outcome measure(s) used; risk of bias......The aim of this study is to systematically collect all published preclinical non-human animal literature on depression to provide an unbiased overview of existing knowledge. A systematic search will be carried out in PubMed and Embase. Studies will be included if they use non-human animal......-analysis of the preclinical studies modelling depression-like behaviours and phenotypes in animals....

  15. An Improved Surface Simplification Method for Facial Expression Animation Based on Homogeneous Coordinate Transformation Matrix and Maximum Shape Operator

    Directory of Open Access Journals (Sweden)

    Juin-Ling Tseng

    2016-01-01

    Full Text Available Facial animation is one of the most popular 3D animation topics researched in recent years. However, when using facial animation, a 3D facial animation model has to be stored. This 3D facial animation model requires many triangles to accurately describe and demonstrate facial expression animation because the face often presents a number of different expressions. Consequently, the costs associated with facial animation have increased rapidly. In an effort to reduce storage costs, researchers have sought to simplify 3D animation models using techniques such as Deformation Sensitive Decimation and Feature Edge Quadric. The studies conducted have examined the problems in the homogeneity of the local coordinate system between different expression models and in the retainment of simplified model characteristics. This paper proposes a method that applies Homogeneous Coordinate Transformation Matrix to solve the problem of homogeneity of the local coordinate system and Maximum Shape Operator to detect shape changes in facial animation so as to properly preserve the features of facial expressions. Further, root mean square error and perceived quality error are used to compare the errors generated by different simplification methods in experiments. Experimental results show that, compared with Deformation Sensitive Decimation and Feature Edge Quadric, our method can not only reduce the errors caused by simplification of facial animation, but also retain more facial features.

  16. Brain in flames – animal models of psychosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Mattei D

    2015-05-01

    Full Text Available Daniele Mattei,1 Regina Schweibold,1,2 Susanne A Wolf1 1Department of Cellular Neuroscience, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany; 2Department of Neurosurgery, Helios Clinics, Berlin, Germany Abstract: The neurodevelopmental hypothesis of schizophrenia posits that schizophrenia is a psychopathological condition resulting from aberrations in neurodevelopmental processes caused by a combination of environmental and genetic factors which proceed long before the onset of clinical symptoms. Many studies discuss an immunological component in the onset and progression of schizophrenia. We here review studies utilizing animal models of schizophrenia with manipulations of genetic, pharmacologic, and immunological origin. We focus on the immunological component to bridge the studies in terms of evaluation and treatment options of negative, positive, and cognitive symptoms. Throughout the review we link certain aspects of each model to the situation in human schizophrenic patients. In conclusion we suggest a combination of existing models to better represent the human situation. Moreover, we emphasize that animal models represent defined single or multiple symptoms or hallmarks of a given disease. Keywords: inflammation, schizophrenia, microglia, animal models 

  17. Animal models for addiction medicine: From vulnerable phenotypes to addicted individuals.

    Science.gov (United States)

    Nader, Michael A

    2016-01-01

    This chapter highlights the use of several animal models of abuse liability. The overall goal is to describe the most frequently used methods, unconditioned behaviors and conditioned behaviors, and how investigators can use these techniques to compare drugs and to understand the mechanisms of action mediating abuse liability. Thus, for each type of animal model described, research will be highlighted on three general features related to the use of the model: (1) determine abuse potential, (2) treatment efficacy, and (3) brain-related changes associated with drug administration. © 2016 Elsevier B.V. All rights reserved.

  18. Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism.

    Science.gov (United States)

    Kim, Ji-Woon; Seung, Hana; Kim, Ki Chan; Gonzales, Edson Luck T; Oh, Hyun Ah; Yang, Sung Min; Ko, Mee Jung; Han, Seol-Heui; Banerjee, Sourav; Shin, Chan Young

    2017-02-01

    Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Diagnosis of abdominal abscess: A large animal model

    International Nuclear Information System (INIS)

    Harper, R.A.; Meek, A.C.; Chidlow, A.D.; Galvin, D.A.J.; McCollum, C.N.

    1988-01-01

    In order to evaluate potential isotopic techniques for the diagnosis of occult sepsis an experimental model in large animals is required. Sponges placed in the abdomen of pigs were injected with mixed colonic bacteria. In 4 animals Kefzol (500 mg IV) and Metronidazole (1 g PR) were administered before the sponges were inserted and compared to 4 given no antibiotics. Finally, in 12 pigs, 20 mls autologous blood was injected into the sponge before antibiotic prophylaxis and bacterial inoculation. 111 In-leucocyte scans and post mortem were then performed 2 weeks later. Without antibiotic cover purulent peritonitis developed in all 4 pigs. Prophylactic antibiotics prevented overwhelming sepsis but at 2 weeks there was only brown fluid surrounding the sponge. Blood added to the sponge produced abscesses in every animal confirmed by leucocytosis of 25.35x10 9 cells/L, 111 In-leucocyte scanning and post mortem. Culturing the thick yellow pus showed a mixed colony of aerobes and anaerobes, similar to those cultured in clinical practice. An intra-abdominal sponge containing blood and faecal organisms in a pig on prophylactic antibiotics reliably produced a chronic abscess. This model is ideal for studies on alternative methods of abscess diagnosis and radiation dosimetry. (orig.)

  20. Management Systems for Organic EggProduction - Aiming to Improve AnimalHealth and Welfare

    DEFF Research Database (Denmark)

    Hegelund, Lene

    one production period. In the second part of the project a generic HACCP system was developed, using an expert panel analysis. The two management tools have very different approaches to improving animal health and welfare, and subsequently different methods, cost and advantages. This makes them...

  1. Recent advances in the development of new transgenic animal technology.

    Science.gov (United States)

    Miao, Xiangyang

    2013-03-01

    Transgenic animal technology is one of the fastest growing biotechnology areas. It is used to integrate exogenous genes into the animal genome by genetic engineering technology so that these genes can be inherited and expressed by offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors in the production of transgenic animals. A variety of transgenic technologies are available. Each has its own advantages and disadvantages and needs further study because of unresolved technical and safety issues. Further studies will allow transgenic technology to explore gene function, animal genetic improvement, bioreactors, animal disease models, and organ transplantation. This article reviews the recently developed animal transgenic technologies, including the germ line stem cell-mediated method to improve efficiency, gene targeting to improve accuracy, RNA interference-mediated gene silencing technology, zinc-finger nuclease gene targeting technology and induced pluripotent stem cell technology. These new transgenic techniques can provide a better platform to develop transgenic animals for breeding new animal varieties and promote the development of medical sciences, livestock production, and other fields.

  2. Animal models for Gaucher disease research

    OpenAIRE

    Farfel-Becker, Tamar; Vitner, Einat B.; Futerman, Anthony H.

    2011-01-01

    Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display sympt...

  3. Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.

    Science.gov (United States)

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner.

  4. Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk.

    Science.gov (United States)

    Shi, Danni; Vine, Donna F

    2012-07-01

    To review rodent animal models of polycystic ovary syndrome (PCOS), with a focus on those associated with the metabolic syndrome and cardiovascular disease risk factors. Review. Rodent models of PCOS. Description and comparison of animal models. Comparison of animal models to clinical phenotypes of PCOS. Animals used to study PCOS include rodents, mice, rhesus monkeys, and ewes. Major methods to induce PCOS in these models include subcutaneous injection or implantation of androgens, estrogens, antiprogesterone, letrozole, prenatal exposure to excess androgens, and exposure to constant light. In addition, transgenic mice models and spontaneous PCOS-like rodent models have also been developed. Rodents are the most economical and widely used animals to study PCOS and ovarian dysfunction. The model chosen to study the development of PCOS and other metabolic parameters remains dependent on the specific etiologic hypotheses being investigated. Rodent models have been shown to demonstrate changes in insulin metabolism, with or without induction of hyperandrogenemia, and limited studies have investigated cardiometabolic risk factors for type 2 diabetes and cardiovascular disease. Given the clinical heterogeneity of PCOS, the utilization of different animal models may be the best approach to further our understanding of the pathophysiologic mechanisms associated with the early etiology of PCOS and cardiometabolic risk. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Animal Models in Forensic Science Research: Justified Use or Ethical Exploitation?

    Science.gov (United States)

    Mole, Calvin Gerald; Heyns, Marise

    2018-05-01

    A moral dilemma exists in biomedical research relating to the use of animal or human tissue when conducting scientific research. In human ethics, researchers need to justify why the use of humans is necessary should suitable models exist. Conversely, in animal ethics, a researcher must justify why research cannot be carried out on suitable alternatives. In the case of medical procedures or therapeutics testing, the use of animal models is often justified. However, in forensic research, the justification may be less evident, particularly when research involves the infliction of trauma on living animals. To determine how the forensic science community is dealing with this dilemma, a review of literature within major forensic science journals was conducted. The frequency and trends of the use of animals in forensic science research was investigated for the period 1 January 2012-31 December 2016. The review revealed 204 original articles utilizing 5050 animals in various forms as analogues for human tissue. The most common specimens utilized were various species of rats (35.3%), pigs (29.3%), mice (17.7%), and rabbits (8.2%) although different specimens were favored in different study themes. The majority of studies (58%) were conducted on post-mortem specimens. It is, however, evident that more needs to be done to uphold the basic ethical principles of reduction, refinement and replacement in the use of animals for research purposes.

  6. Strategies to enable the adoption of animal biotechnology to sustainably improve global food safety and security.

    Science.gov (United States)

    Tizard, Mark; Hallerman, Eric; Fahrenkrug, Scott; Newell-McGloughlin, Martina; Gibson, John; de Loos, Frans; Wagner, Stefan; Laible, Götz; Han, Jae Yong; D'Occhio, Michael; Kelly, Lisa; Lowenthal, John; Gobius, Kari; Silva, Primal; Cooper, Caitlin; Doran, Tim

    2016-10-01

    The ability to generate transgenic animals has existed for over 30 years, and from those early days many predicted that the technology would have beneficial applications in agriculture. Numerous transgenic agricultural animals now exist, however to date only one product from a transgenic animal has been approved for the food chain, due in part to cumbersome regulations. Recently, new techniques such as precision breeding have emerged, which enables the introduction of desired traits without the use of transgenes. The rapidly growing human population, environmental degradation, and concerns related to zoonotic and pandemic diseases have increased pressure on the animal agriculture sector to provide a safe, secure and sustainable food supply. There is a clear need to adopt transgenic technologies as well as new methods such as gene editing and precision breeding to meet these challenges and the rising demand for animal products. To achieve this goal, cooperation, education, and communication between multiple stakeholders-including scientists, industry, farmers, governments, trade organizations, NGOs and the public-is necessary. This report is the culmination of concepts first discussed at an OECD sponsored conference and aims to identify the main barriers to the adoption of animal biotechnology, tactics for navigating those barriers, strategies to improve public perception and trust, as well as industry engagement, and actions for governments and trade organizations including the OECD to harmonize regulations and trade agreements. Specifically, the report focuses on animal biotechnologies that are intended to improve breeding and genetics and currently are not routinely used in commercial animal agriculture. We put forward recommendations on how scientists, regulators, and trade organizations can work together to ensure that the potential benefits of animal biotechnology can be realized to meet the future needs of agriculture to feed the world.

  7. Modeling DNA structure and processes through animation and kinesthetic visualizations

    Science.gov (United States)

    Hager, Christine

    There have been many studies regarding the effectiveness of visual aids that go beyond that of static illustrations. Many of these have been concentrated on the effectiveness of visual aids such as animations and models or even non-traditional visual aid activities like role-playing activities. This study focuses on the effectiveness of three different types of visual aids: models, animation, and a role-playing activity. Students used a modeling kit made of Styrofoam balls and toothpicks to construct nucleotides and then bond nucleotides together to form DNA. Next, students created their own animation to depict the processes of DNA replication, transcription, and translation. Finally, students worked in teams to build proteins while acting out the process of translation. Students were given a pre- and post-test that measured their knowledge and comprehension of the four topics mentioned above. Results show that there was a significant gain in the post-test scores when compared to the pre-test scores. This indicates that the incorporated visual aids were effective methods for teaching DNA structure and processes.

  8. Image Quality Improvement on OpenGL-Based Animations by Using CUDA Architecture

    Directory of Open Access Journals (Sweden)

    Taner UÇKAN

    2016-04-01

    Full Text Available 2D or 3D rendering technology is used for graphically modelling many physical phenomena occurring in real life by means of the computers. On the other hand, the ever-increasing intensity of the graphics applications require that the image quality of the so-called modellings is enhanced and they are performed more quickly. In this direction, a new software and hardware-based architecture called CUDA has been introduced by Nvidia at the end of 2006. Thanks to this architecture, larger number of graphics processors has started contributing towards the parallel solutions of the general-purpose problems. In this study, this new parallel computing architecture is taken into consideration and an animation application consisting of humanoid robots with different behavioral characteristics is developed using the OpenGL library in C++. This animation is initially implemented on a single serial CPU and then parallelized using the CUDA architecture. Eventually, the serial and the parallel versions of the same animation are compared against each other on the basis of the number of image frames per second. The results reveal that the parallel application is by far the best yielding high quality images.

  9. Improving the use of economics in animal health - Challenges in research, policy and education.

    Science.gov (United States)

    Rushton, Jonathan

    2017-02-01

    The way that an economist and an animal health professional use economics differs and creates frustrations. The economist is in search of optimizing resource allocation in the management of animal health and disease problems with metrics associated with the productivity of key societal resources of labour and capital. The animal health professional have a strong belief that productivity can be improved with the removal of pathogens. These differences restrict how well economics is used in animal health, and the question posed is whether this matters. The paper explores the question by looking at the changing role of animals in society and the associated change of the animal health professional's activities. It then questions if the current allocation of scarce resources for animal health are adequately allocated for societies and whether currently available data are sufficient for good allocation. A rapid review of the data on disease impacts - production losses and costs of human reaction - indicate that the data are sparse collected in different times and geographical regions. This limits what can be understood on the productivity of the economic resources used for animal health and this needs to be addressed with more systematic collection of data on disease losses and costs of animal health systems. Ideally such a process should learn lessons from the way that human health has made estimates of the burden of diseases and their capture of data on the costs of human health systems. Once available data on the global burden of animal diseases and the costs of animal health systems would allow assessments of individual disease management processes and the productivity of wider productivity change. This utopia should be aimed at if animal health is to continue to attract and maintain adequate resources. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Linking Essential Tremor to the Cerebellum-Animal Model Evidence.

    Science.gov (United States)

    Handforth, Adrian

    2016-06-01

    In this review, we hope to stimulate interest in animal models as opportunities to understand tremor mechanisms within the cerebellar system. We begin by considering the harmaline model of essential tremor (ET), which has ET-like anatomy and pharmacology. Harmaline induces the inferior olive (IO) to burst fire rhythmically, recruiting rhythmic activity in Purkinje cells (PCs) and deep cerebellar nuclei (DCN). This model has fostered the IO hypothesis of ET, which postulates that factors that promote excess IO, and hence PC complex spike synchrony, also promote tremor. In contrast, the PC hypothesis postulates that partial PC cell loss underlies tremor of ET. We describe models in which chronic partial PC loss is associated with tremor, such as the Weaver mouse, and others with PC loss that do not show tremor, such as the Purkinje cell degeneration mouse. We postulate that partial PC loss with tremor is associated with terminal axonal sprouting. We then discuss tremor that occurs with large lesions of the cerebellum in primates. This tremor has variable frequency and is an ataxic tremor not related to ET. Another tremor type that is not likely related to ET is tremor in mice with mutations that cause prolonged synaptic GABA action. This tremor is probably due to mistiming within cerebellar circuitry. In the final section, we catalog tremor models involving neurotransmitter and ion channel perturbations. Some appear to be related to the IO hypothesis of ET, while in others tremor may be ataxic or due to mistiming. In summary, we offer a tentative framework for classifying animal action tremor, such that various models may be considered potentially relevant to ET, subscribing to IO or PC hypotheses, or not likely relevant, as with mistiming or ataxic tremor. Considerable further research is needed to elucidate the mechanisms of tremor in animal models.

  11. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  12. Animal models for oral transmission of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Sarah E F D'Orazio

    2014-02-01

    Full Text Available Listeria monocytogenes has been recognized as a food borne pathogen in humans since the 1980s, but we still understand very little about oral transmission of L. monocytogenes or the host factors that determine susceptibility to gastrointestinal infection, due to the lack of an appropriate small animal model of oral listeriosis. Early feeding trials suggested that many animals were highly resistant to oral infection, and the more reproducible intravenous or intraperitoneal routes of inoculation soon came to be favored. There are a fair number of previously published studies using an oral infection route, but the work varies widely in terms of bacterial strain choice, the methods used for oral transmission, and various manipulations used to enhance infectivity. This mini review will summarize the published literature using oral routes of L. monocytogenes infection and will highlight recent technological advances that have made oral infection a more attractive model system.

  13. A review of animal models used to evaluate potential allergenicity of genetically modified organisms (GMOs)

    DEFF Research Database (Denmark)

    Marsteller, Nathan; Bøgh, Katrine Lindholm; Goodman, Richard E.

    2017-01-01

    Food safety regulators request prediction of allergenicity for newly expressed proteins in genetically modified (GM) crops and in novel foods. Some have suggested using animal models to assess potential allergenicity. A variety of animal models have been used in research to evaluate sensitisation...... of genetically modified organisms (GMOs).......Food safety regulators request prediction of allergenicity for newly expressed proteins in genetically modified (GM) crops and in novel foods. Some have suggested using animal models to assess potential allergenicity. A variety of animal models have been used in research to evaluate sensitisation...

  14. Maximum-entropy description of animal movement.

    Science.gov (United States)

    Fleming, Chris H; Subaşı, Yiğit; Calabrese, Justin M

    2015-03-01

    We introduce a class of maximum-entropy states that naturally includes within it all of the major continuous-time stochastic processes that have been applied to animal movement, including Brownian motion, Ornstein-Uhlenbeck motion, integrated Ornstein-Uhlenbeck motion, a recently discovered hybrid of the previous models, and a new model that describes central-place foraging. We are also able to predict a further hierarchy of new models that will emerge as data quality improves to better resolve the underlying continuity of animal movement. Finally, we also show that Langevin equations must obey a fluctuation-dissipation theorem to generate processes that fall from this class of maximum-entropy distributions when the constraints are purely kinematic.

  15. Brain glucose metabolism in an animal model of depression.

    Science.gov (United States)

    Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

    2015-06-04

    An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

  16. Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

    Science.gov (United States)

    2015-01-01

    Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

  17. Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

    Science.gov (United States)

    Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

    2014-03-25

    Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

  18. Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

    Directory of Open Access Journals (Sweden)

    Nabeela Nathoo

    2014-01-01

    Full Text Available There are exciting new advances in multiple sclerosis (MS resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

  19. Animal models for human genetic diseases | Sharif | African Journal ...

    African Journals Online (AJOL)

    The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

  20. Using human brain imaging studies as a guide towards animal models of schizophrenia

    Science.gov (United States)

    BOLKAN, Scott S.; DE CARVALHO, Fernanda D.; KELLENDONK, Christoph

    2015-01-01

    Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients. PMID:26037801

  1. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Directory of Open Access Journals (Sweden)

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  2. Animal models for clinical and gestational diabetes: maternal and fetal outcomes.

    Science.gov (United States)

    Kiss, Ana Ci; Lima, Paula Ho; Sinzato, Yuri K; Takaku, Mariana; Takeno, Marisa A; Rudge, Marilza Vc; Damasceno, Débora C

    2009-10-19

    Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Experimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women

  3. Animal models for clinical and gestational diabetes: maternal and fetal outcomes

    Directory of Open Access Journals (Sweden)

    Kiss Ana CI

    2009-10-01

    Full Text Available Abstract Background Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl and mild diabetes (glycemia between 120 and 300 mg/dl on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. Methods On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16, severe (n = 50 and mild diabetes (n = 30. At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Results Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Conclusion Experimental models of severe diabetes during pregnancy

  4. New methods and reagents to improve the ferret model for human influenza infections

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Kirkeby, Svend; Aasted, Bent

    The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, ...... improvements of the model will aim at establishing a reliable RT-PCR for ferret cytokines, as well as investigating the location of influenza receptors and viral particles in the upper and lower respiratory tract via immunohistochemistry......The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, CD...

  5. How can animal models inform on the transition to chronic symptoms in whiplash?

    Science.gov (United States)

    Winkelstein, Beth A.

    2011-01-01

    Study Design A non-systematic review of the literature. Objective The objective was to present general schema for mechanisms of whiplash pain and review the role of animal models in understanding the development of chronic pain from whiplash injury. Summary of Background Data Extensive biomechanical and clinical studies of whiplash have been performed to understand the injury mechanisms and symptoms of whiplash injury. However, only recently have animal models of this painful disorder been developed based on other pain models in the literature. Methods A non-systematic review was performed and findings were integrated to formulate a generalized picture of mechanisms by chronic whiplash pain develops from mechanical tissue injuries. Results The development of chronic pain from tissue injuries in the neck due to whiplash involves complex interactions between the injured tissue and spinal neuroimmune circuits. A variety of animal models are beginning to define these mechanisms. Conclusion Continued work is needed in developing appropriate animal models to investigate chronic pain from whiplash injuries and care must be taken to determine whether such models aim to model the injury event or the pain symptom. PMID:22020616

  6. The guinea pig as an animal model for developmental and reproductive toxicology studies.

    Science.gov (United States)

    Rocca, Meredith S; Wehner, Nancy G

    2009-04-01

    Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

  7. An Experimental Animal Model for Abdominal Fascia Healing after Surgery

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H-C; Klein, M

    2013-01-01

    be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia......Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

  8. Towards an Ethological Animal Model of Depression? A Study on Horses

    Science.gov (United States)

    Fureix, Carole; Jego, Patrick; Henry, Séverine; Lansade, Léa; Hausberger, Martine

    2012-01-01

    Background Recent reviews question current animal models of depression and emphasise the need for ethological models of mood disorders based on animals living under natural conditions. Domestic horses encounter chronic stress, including potential stress at work, which can induce behavioural disorders (e.g. “apathy”). Our pioneering study evaluated the potential of domestic horses in their usual environment to become an ethological model of depression by testing this models’ face validity (i.e. behavioural similarity with descriptions of human depressive states). Methodology/Principal Findings We observed the spontaneous behaviour of 59 working horses in their home environment, focusing on immobility bouts of apparent unresponsiveness when horses displayed an atypical posture (termed withdrawn hereafter), evaluated their responsiveness to their environment and their anxiety levels, and analysed cortisol levels. Twenty-four percent of the horses presented the withdrawn posture, also characterized by gaze, head and ears fixity, a profile that suggests a spontaneous expression of “behavioural despair”. When compared with control “non-withdrawn” horses from the same stable, withdrawn horses appeared more indifferent to environmental stimuli in their home environment but reacted more emotionally in more challenging situations. They exhibited lower plasma cortisol levels. Withdrawn horses all belonged to the same breed and females were over-represented. Conclusions/Significance Horse might be a useful potential candidate for an animal model of depression. Face validity of this model appeared good, and potential genetic input and high prevalence of these disorders in females add to the convergence. At a time when current animal models of depression are questioned and the need for novel models is expressed, this study suggests that novel models and biomarkers could emerge from ethological approaches in home environments. PMID:22761752

  9. Infectious diseases among animals : combining models with data

    NARCIS (Netherlands)

    Koeijer, A.A. de

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the

  10. Animal models of chronic wound care: the application of biofilms in clinical research

    Directory of Open Access Journals (Sweden)

    Trøstrup H

    2016-11-01

    Full Text Available Hannah Trøstrup,1 Kim Thomsen,1 Henrik Calum,2 Niels Høiby,1,3 Claus Moser1 1Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, 3Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark Abstract: Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s, and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should

  11. An animal model for the neuromodulation of neurogenic bladder dysfunction.

    Science.gov (United States)

    Zvara, P; Sahi, S; Hassouna, M M

    1998-08-01

    To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

  12. Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics

    Science.gov (United States)

    2018-01-01

    Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact. PMID:29513704

  13. Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics.

    Science.gov (United States)

    Frisk, Mikael; Jonsson, Annie; Sellman, Stefan; Flisberg, Patrik; Rönnqvist, Mikael; Wennergren, Uno

    2018-01-01

    Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact.

  14. Draught animals and welfare.

    Science.gov (United States)

    Ramaswamy, N S

    1994-03-01

    In fifty developing countries, which contain half of the total human population of the world, there is a heavy dependence on draught animals as an energy source. These animals are used for agriculture operations in 52% of cultivated areas of the world, as well as for hauling 25 million carts. This situation is likely to continue for at least another fifty years. The work performed annually by these draught animals would require 20 million tons of petroleum, valued at US$6 billion, if it were performed by motorized vehicles. The poor working conditions of these animals often adversely affect their productivity. The application of improved technology and better management (i.e. through better feed and health services, and improved design of agricultural implements and carts) could considerably improve the welfare of these animals. Improved systems would generate sufficient benefits for the economy to justify the required investment. High priority should therefore be given to draught animal power in the economic development agenda.

  15. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan Jana

    2012-01-01

    Full Text Available Angelman syndrome (AS is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.

  16. Bayesian spatial models of the association between interpersonal violence, animal abuse and social vulnerability in São Paulo, Brazil.

    Science.gov (United States)

    Baquero, Oswaldo Santos; Ferreira, Fernando; Robis, Marcelo; Neto, José Soares Ferreira; Onell, Jason Ardila

    2018-04-01

    Animal abuse adversely affects animal health and welfare and has been associated with interpersonal violence in studies of individuals. However, if that association also depends on sociocultural contexts and can be detected on a geographic scale, a wider source of data can be used to identify risk areas to support the surveillance of both types of violence. In this study, we evaluated the association between interpersonal violence notifications, animal abuse notifications and an index of social vulnerability in São Paulo City, on a geographic scale, using Bayesian spatial models. The social vulnerability index was a risk factor for the number of interpersonal violence notifications and presented a dose-response pattern. The number of animal abuse notifications was also a risk factor for the number of interpersonal violence notifications, even after controlling for the social vulnerability index. The incorporation of spatial effects produced marked improvements in model performance metrics and allowed the identification of excess risk clusters. Geographical data on notifications on either animal abuse or interpersonal violence should be considered incitement for investigations and interventions of both types of violence. We suggest that notifications of animal abuse be based on an explicit definition and classification, as well as on objective measurements that allow a better understanding of the species and type of abuse involved, the animal health consequences, and the context in which they occurred. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Limitations and possibilities of animal models for human allergenic risk evaluation

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Kroghsbo, Stine; Bøgh, Katrine Lindholm

    2012-01-01

    evaluation. One of the pitfalls may be the premise that an animal model needs to mimic the disease. Chemical contact sensitizers may be predicted in an animal test, the Local Lymph Node Assay (LLNA). This assay is based on detailed mechanistic knowledge of contact sensitization including knowledge on dose...

  18. Plant G-Proteins Come of Age: Breaking the Bond with Animal Models.

    Science.gov (United States)

    Trusov, Yuri; Botella, José R

    2016-01-01

    G-proteins are universal signal transducers mediating many cellular responses. Plant G-protein signaling has been modeled on the well-established animal paradigm but accumulated experimental evidence indicates that G-protein-dependent signaling in plants has taken a very different evolutionary path. Here we review the differences between plant and animal G-proteins reported over past two decades. Most importantly, while in animal systems the G-protein signaling cycle is activated by seven transmembrane-spanning G-protein coupled receptors, the existence of these type of receptors in plants is highly controversial. Instead plant G-proteins have been proven to be functionally associated with atypical receptors such as the Arabidopsis RGS1 and a number of receptor-like kinases. We propose that, instead of the GTP/GDP cycle used in animals, plant G-proteins are activated/de-activated by phosphorylation/de-phosphorylation. We discuss the need of a fresh new look at these signaling molecules and provide a hypothetical model that departs from the accepted animal paradigm.

  19. Biochemical correlates in an animal model of depression

    International Nuclear Information System (INIS)

    Johnson, J.O.

    1986-01-01

    A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action

  20. Animal Models of Speech and Vocal Communication Deficits Associated With Psychiatric Disorders.

    Science.gov (United States)

    Konopka, Genevieve; Roberts, Todd F

    2016-01-01

    Disruptions in speech, language, and vocal communication are hallmarks of several neuropsychiatric disorders, most notably autism spectrum disorders. Historically, the use of animal models to dissect molecular pathways and connect them to behavioral endophenotypes in cognitive disorders has proven to be an effective approach for developing and testing disease-relevant therapeutics. The unique aspects of human language compared with vocal behaviors in other animals make such an approach potentially more challenging. However, the study of vocal learning in species with analogous brain circuits to humans may provide entry points for understanding this human-specific phenotype and diseases. We review animal models of vocal learning and vocal communication and specifically link phenotypes of psychiatric disorders to relevant model systems. Evolutionary constraints in the organization of neural circuits and synaptic plasticity result in similarities in the brain mechanisms for vocal learning and vocal communication. Comparative approaches and careful consideration of the behavioral limitations among different animal models can provide critical avenues for dissecting the molecular pathways underlying cognitive disorders that disrupt speech, language, and vocal communication. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. FAO/IAEA international symposium on sustainable improvement of animal production and health. Synopses

    International Nuclear Information System (INIS)

    2009-01-01

    The on-going 'Livestock Revolution', a demand-driven increase in livestock production, especially in developing countries, presents both opportunities and risks. The shift in the human diet from plant-based protein sources to animal-based protein sources, consumer demand for safe and quality animal products, and expanding markets for livestock products have raised several challenges such as; cost-effective production of safe and quality animal products, control of emerging and zoonotic diseases, and efficient management of impact of livestock on the environment. However, these changes have also provided many opportunities to benefit the local economy and producers, and reduce poverty. New challenges and opportunities demand innovative ideas and approaches, and mechanisms to take this knowledge to potential users. Many of the approaches will be multidisciplinary in nature and require collaboration with specialists in areas other than animal scientists. Livestock production in developing countries is constrained by low genetic potential of animals, poor nutrition, poor husbandry and infectious diseases. Nuclear techniques, when applied in conjunction with conventional methods, can identify critical points in these areas that can be targeted for cost-effective improvements and interventions. Thus the challenge is to use such technologies to enhance food security and alleviate poverty by supporting sustainable livestock production systems in developing countries through strategic and applied research, technology transfer and capacity building. Topics addressed at the symposium: - Interactions among nutrition, reproduction and genotype; - Livestock-environment interaction / productivity/ climate (water/ land/ plants/heat/ altitude); - Detection and control of transboundary animal diseases, including zoonoses; - Animal product safety and food quality. Each of the papers published in this book of synopses has been indexed separately

  2. A parsimonious approach to modeling animal movement data.

    Directory of Open Access Journals (Sweden)

    Yann Tremblay

    Full Text Available Animal tracking is a growing field in ecology and previous work has shown that simple speed filtering of tracking data is not sufficient and that improvement of tracking location estimates are possible. To date, this has required methods that are complicated and often time-consuming (state-space models, resulting in limited application of this technique and the potential for analysis errors due to poor understanding of the fundamental framework behind the approach. We describe and test an alternative and intuitive approach consisting of bootstrapping random walks biased by forward particles. The model uses recorded data accuracy estimates, and can assimilate other sources of data such as sea-surface temperature, bathymetry and/or physical boundaries. We tested our model using ARGOS and geolocation tracks of elephant seals that also carried GPS tags in addition to PTTs, enabling true validation. Among pinnipeds, elephant seals are extreme divers that spend little time at the surface, which considerably impact the quality of both ARGOS and light-based geolocation tracks. Despite such low overall quality tracks, our model provided location estimates within 4.0, 5.5 and 12.0 km of true location 50% of the time, and within 9, 10.5 and 20.0 km 90% of the time, for above, equal or below average elephant seal ARGOS track qualities, respectively. With geolocation data, 50% of errors were less than 104.8 km (<0.94 degrees, and 90% were less than 199.8 km (<1.80 degrees. Larger errors were due to lack of sea-surface temperature gradients. In addition we show that our model is flexible enough to solve the obstacle avoidance problem by assimilating high resolution coastline data. This reduced the number of invalid on-land location by almost an order of magnitude. The method is intuitive, flexible and efficient, promising extensive utilization in future research.

  3. Endometriosis research: animal models for the study of a complex disease.

    Science.gov (United States)

    Tirado-González, Irene; Barrientos, Gabriela; Tariverdian, Nadja; Arck, Petra C; García, Mariana G; Klapp, Burghard F; Blois, Sandra M

    2010-11-01

    Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Review: To be or not to be an identifiable model. Is this a relevant question in animal science modelling?

    Science.gov (United States)

    Muñoz-Tamayo, R; Puillet, L; Daniel, J B; Sauvant, D; Martin, O; Taghipoor, M; Blavy, P

    2018-04-01

    What is a good (useful) mathematical model in animal science? For models constructed for prediction purposes, the question of model adequacy (usefulness) has been traditionally tackled by statistical analysis applied to observed experimental data relative to model-predicted variables. However, little attention has been paid to analytic tools that exploit the mathematical properties of the model equations. For example, in the context of model calibration, before attempting a numerical estimation of the model parameters, we might want to know if we have any chance of success in estimating a unique best value of the model parameters from available measurements. This question of uniqueness is referred to as structural identifiability; a mathematical property that is defined on the sole basis of the model structure within a hypothetical ideal experiment determined by a setting of model inputs (stimuli) and observable variables (measurements). Structural identifiability analysis applied to dynamic models described by ordinary differential equations (ODEs) is a common practice in control engineering and system identification. This analysis demands mathematical technicalities that are beyond the academic background of animal science, which might explain the lack of pervasiveness of identifiability analysis in animal science modelling. To fill this gap, in this paper we address the analysis of structural identifiability from a practitioner perspective by capitalizing on the use of dedicated software tools. Our objectives are (i) to provide a comprehensive explanation of the structural identifiability notion for the community of animal science modelling, (ii) to assess the relevance of identifiability analysis in animal science modelling and (iii) to motivate the community to use identifiability analysis in the modelling practice (when the identifiability question is relevant). We focus our study on ODE models. By using illustrative examples that include published

  5. Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

    2013-01-01

    Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

  6. Improvement and application of an acute blood stasis rat model aligned with the 3Rs (reduction, refinement and replacement) of humane animal experimentation.

    Science.gov (United States)

    Huang, Shuai; Xu, Feng; Wang, Yin-Ye; Shang, Ming-Ying; Wang, Chao-Qun; Wang, Xuan; Cai, Shao-Qing

    2014-12-23

    To establish a novel cardiocentesis method for withdrawing venous blood from the right atrium, and to improve an acute blood stasis rat model using an ice bath and epinephrine hydrochloride (Epi) while considering the 3Rs (reduction, refinement, and replacement) of humane animal experimentation. An acute blood stasis model was established in male Sprague-Dawley rats by subcutaneous injection (s.c.) Epi (1.2 mg/kg) administration at 0 h, followed by a 5-min exposure to an ice-bath at 2 h and s.c. Epi administration at 4 h. Control rats received physiological saline. Rats were fasted overnight and treated with Angelicae Sinensis Lateralis Radix (ASLR) and Pheretima the following day. Venous blood was collected using our novel cardiocentesis method and used to test whole blood viscosity (WBV), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) content. The rats survived the novel cardiocentesis technique; WBV value returned to normal while hematological parameters such as hemoglobin level and red blood cell count were restored to >94% of the corresponding values in normal rats following a 14-day recovery. Epi (1.2 mg/kg, s.c.) combined with a 5-min exposure to the ice bath replicated the acute blood stasis rat model and was associated with the highest WBV value. In rats showing acute blood stasis, ASLR treatment [4 g/(kg·d) for 8 days] decreased WBV by 9.98%, 11.09%, 9.34%, 9.00%, 7.66%, and 7.03% (P<0.05), while Pheretima treatment [2.6 g/(kg·d), for 8 days] decreased WBV by 25.49%, 25.94%, 16.28%, 17.76%, 11.07%, and 7.89% (P<0.01) at shear rates of 1, 3, 10, 30, 100, and 180 s -1 , respectively. Furthermore, Pheretima treatment increased APTT significantly (P<0.01). We presented a stable, reproducible, and improved acute blood stasis rat model, which could be applied to screen drugs for promoting blood circulation and eliminating blood stasis.

  7. Pharmacokinetic models relevant to toxicity and metabolism for uranium in humans and animals

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Lipsztein, J.; Bertelli, L.

    1988-01-01

    The aim of this paper is to summarize pharmacokinetic models of uranium metabolism. Fortunately, others have recently reviewed metabolic models of all types, not just pharmacokinetic models. Their papers should be consulted for greater biological detail than is possible here. Improvements in the models since these other papers are noted. Models for assessing the biological consequences of exposure should account for the kinetics of intake by ingestion, inhalation, and injection, and the chemical form of uranium; predict the time dependent concentration in red blood cells, plasma, urine, kidney, bone and other organs (or compartments); and be adaptable to calculating these concentrations for varying regimens of intake. The biological parameters in the models come from metabolic data in humans and animals. Some of these parameters are reasonably well defined. For example, the cumulative urinary excretion at 24 hours post injection of soluble uranium in man is about 70%, the absorbed fraction for soluble uranium ingested by man in drinking water during normal dietary conditions is about 1%, and the half time in the mammalian kidney is several days. 17 refs., 8 figs

  8. Animal Modeling and Neurocircuitry of Dual Diagnosis

    Science.gov (United States)

    Chambers, R. Andrew

    2010-01-01

    Dual diagnosis is a problem of tremendous depth and scope, spanning many classes of mental disorders and addictive drugs. Animal models of psychiatric disorders studied in addiction paradigms suggest a unitary nature of mental illness and addiction vulnerability both on the neurocircuit and clinical-behavioral levels. These models provide platforms for exploring the interactive roles of biological, environmental and developmental factors on neurocircuits commonly involved in psychiatric and addiction diseases. While suggestive of the artifice of segregated research, training, and clinical cultures between psychiatric and addiction fields, this research may lead to more parsimonious, integrative and preventative treatments for dual diagnosis. PMID:20585464

  9. Blood-CNS Barrier Impairment in ALS Patients versus an Animal Model

    Directory of Open Access Journals (Sweden)

    Svitlana eGarbuzova-Davis

    2014-02-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a severe neurodegenerative disease with a compli-cated and poorly understood pathogenesis. Recently, alterations in the blood-Central Nervous System barrier (B-CNS-B have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been deter-mined in mutant SOD1 rodent models, identifying barrier damage during disease develop-ment which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS has been limited. We recently showed structural and functional impairment in postmortem gray and white mat-ter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degenera-tion, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages are indicated in both mutant SOD1 animal models of ALS and SALS pa-tients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnor-malities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood-CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.

  10. Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.

    Directory of Open Access Journals (Sweden)

    William P Melega

    Full Text Available Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8 which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4 concurrently receiving continuous low frequency (50 Hz VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05, suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.

  11. Metabolic Effects of Inflammation on Vitamin A and Carotenoids in Humans and Animal Models.

    Science.gov (United States)

    Rubin, Lewis P; Ross, A Catharine; Stephensen, Charles B; Bohn, Torsten; Tanumihardjo, Sherry A

    2017-03-01

    The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency. On the other hand, inflammation causes impaired VA absorption and urinary losses that can precipitate VA deficiency in at-risk groups of children. Many epidemiologic studies have suggested that high dietary carotenoid intake and elevated plasma concentrations are correlated with a decreased risk of several chronic diseases; however, large-scale carotenoid supplementation trials have been unable to confirm the health benefits and in some cases resulted in controversial results. However, it has been documented that dietary carotenoids and retinoids play important roles in innate and acquired immunity and in the body's response to inflammation. Although animal models have been useful in investigating retinoid effects on developmental immunity, it is more challenging to tease out the effects of carotenoids because of differences in the absorption, kinetics, and metabolism between humans and animal models. The current understanding of the relations between inflammation and retinoid and carotenoid metabolism and status are the topics of this review. © 2017 American Society for Nutrition.

  12. Animal models of enterovirus 71 infection: applications and limitations

    Science.gov (United States)

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

  13. Analyzer-based imaging of spinal fusion in an animal model

    International Nuclear Information System (INIS)

    Kelly, M E; Beavis, R C; Allen, L A; Fiorella, David; Schueltke, E; Juurlink, B H; Chapman, L D; Zhong, Z

    2008-01-01

    Analyzer-based imaging (ABI) utilizes synchrotron radiation sources to create collimated monochromatic x-rays. In addition to x-ray absorption, this technique uses refraction and scatter rejection to create images. ABI provides dramatically improved contrast over standard imaging techniques. Twenty-one adult male Wistar rats were divided into four experimental groups to undergo the following interventions: (1) non-injured control, (2) decortication alone, (3) decortication with iliac crest bone grafting and (4) decortication with iliac crest bone grafting and interspinous wiring. Surgical procedures were performed at the L5-6 level. Animals were killed at 2, 4 and 6 weeks after the intervention and the spine muscle blocks were excised. Specimens were assessed for the presence of fusion by (1) manual testing, (2) conventional absorption radiography and (3) ABI. ABI showed no evidence of bone fusion in groups 1 and 2 and showed solid or possibly solid fusion in subjects from groups 3 and 4 at 6 weeks. Metal artifacts were not present in any of the ABI images. Conventional absorption radiographs did not provide diagnostic quality imaging of either the graft material or fusion masses in any of the specimens in any of the groups. Synchrotron-based ABI represents a novel imaging technique which can be used to assess spinal fusion in a small animal model. ABI produces superior image quality when compared to conventional radiographs

  14. Analyzer-based imaging of spinal fusion in an animal model

    Science.gov (United States)

    Kelly, M. E.; Beavis, R. C.; Fiorella, David; Schültke, E.; Allen, L. A.; Juurlink, B. H.; Zhong, Z.; Chapman, L. D.

    2008-05-01

    Analyzer-based imaging (ABI) utilizes synchrotron radiation sources to create collimated monochromatic x-rays. In addition to x-ray absorption, this technique uses refraction and scatter rejection to create images. ABI provides dramatically improved contrast over standard imaging techniques. Twenty-one adult male Wistar rats were divided into four experimental groups to undergo the following interventions: (1) non-injured control, (2) decortication alone, (3) decortication with iliac crest bone grafting and (4) decortication with iliac crest bone grafting and interspinous wiring. Surgical procedures were performed at the L5-6 level. Animals were killed at 2, 4 and 6 weeks after the intervention and the spine muscle blocks were excised. Specimens were assessed for the presence of fusion by (1) manual testing, (2) conventional absorption radiography and (3) ABI. ABI showed no evidence of bone fusion in groups 1 and 2 and showed solid or possibly solid fusion in subjects from groups 3 and 4 at 6 weeks. Metal artifacts were not present in any of the ABI images. Conventional absorption radiographs did not provide diagnostic quality imaging of either the graft material or fusion masses in any of the specimens in any of the groups. Synchrotron-based ABI represents a novel imaging technique which can be used to assess spinal fusion in a small animal model. ABI produces superior image quality when compared to conventional radiographs.

  15. Animal breeding strategies can improve meat quality attributes within entire populations.

    Science.gov (United States)

    Berry, D P; Conroy, S; Pabiou, T; Cromie, A R

    2017-10-01

    The contribution of animal breeding to changes in animal performance is well documented across a range of species. Once genetic variation in a trait exists, then breeding to improve the characteristics of that trait is possible, if so desired. Considerable genetic variation exists in a range of meat quality attributes across a range of species. The genetic variation that exists for meat quality is as large as observed for most performance traits; thus, within a well-structured breeding program, rapid genetic gain for meat quality could be possible. The rate of genetic gain can be augmented through the integration of DNA-based technologies into the breeding program; such DNA-based technologies should, however, be based on thousands of DNA markers dispersed across the entire genome. Genetic and genomic technologies can also have beneficial impact outside the farm gate as a tool to segregate carcasses or meat cuts based on expected meat quality features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Stimulation of postsynapse adrenergic α2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Kawaura, Kazuaki; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

    2014-08-15

    A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR) pups has been used as an animal model of attention deficit hyperactivity disorder (ADHD). However, the roles of noradrenergic systems, which are involved in the pathophysiology of ADHD, have not been investigated in this model. In the present study, the effects of adrenergic α2 receptor stimulation, which has been an effective treatment for ADHD, on attention/cognition performance were investigated in this model. Moreover, neuronal mechanisms mediated through adrenergic α2 receptors were investigated. We evaluated the effects of both clonidine, a non-selective adrenergic α2 receptor agonist, and guanfacine, a selective adrenergic α2A receptor agonist, using a 5-trial inhibitory avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency, compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine significantly prolonged the transfer latency of juvenile SHR. The effects of clonidine and guanfacine were significantly blocked by pretreatment with an adrenergic α2A receptor antagonist. In contrast, the effect of clonidine was not attenuated by pretreatment with an adrenergic α2B receptor antagonist, or an adrenergic α2C receptor antagonist, while it was attenuated by a non-selective adrenergic α2 receptor antagonist. Furthermore, the effects of neither clonidine nor guanfacine were blocked by pretreatment with a selective noradrenergic neurotoxin. These results suggest that the stimulation of the adrenergic α2A receptor improves the attention/cognition performance of juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic, rather than presynaptic, adrenergic α2A receptor is involved in this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Control of Groundwater Pollution from Animal Feeding Operations: A Farm-Level Dynamic Model for Policy Analysis

    Science.gov (United States)

    Wang, J.; Baerenklau, K.

    2012-12-01

    Consolidation in livestock production generates higher farm incomes due to economies of scale, but it also brings waste disposal problems. Over-application of animal waste on adjacent land produces adverse environmental and health effects, including groundwater nitrate pollution. The situation is particularly noticeable in California. In respond to this increasingly severe problem, EPA published a type of command-and-control regulation for concentrated animal feeding operations (CAFOs) in 2003. The key component of the regulation is its nutrient management plans (NMPs), which intend to limit the land application rates of animal waste. Although previous studies provide a full perspective on potential economic impacts for CAFOs to meet nutrient standards, their models are static and fail to reflect changes in management practices other than spreading manure on additional land and changing cropping patterns. We develop a dynamic environmental-economic modeling framework for representative CAFOs. The framework incorporates four models (i.e., animal model, crop model, hydrologic model, and economic model) that include various components such as herd management, manure handling system, crop rotation, water sources, irrigation system, waste disposal options, and pollutant emissions. We also include the dynamics of soil characteristics in the rootzone as well as the spatial heterogeneity of the irrigation system. The operator maximizes discounted total farm profit over multiple periods subject to environmental regulations. Decision rules from the dynamic optimization problem demonstrate best management practices for CAFOs to improve their economic and environmental performance. Results from policy simulations suggest that direct quantity restrictions of emission or incentive-based emission policies are much more cost-effective than the standard approach of limiting the amount of animal waste that may be applied to fields (as shown in the figure below); reason being

  18. Improving the Reliability of Tinnitus Screening in Laboratory Animals.

    Science.gov (United States)

    Jones, Aikeen; May, Bradford J

    2017-02-01

    Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal's natural tendency to respond to the "sound" of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display sound-conditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus "fills in the gap." Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal's tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

  19. Life sciences research in space: The requirement for animal models

    Science.gov (United States)

    Fuller, C. A.; Philips, R. W.; Ballard, R. W.

    1987-01-01

    Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.

  20. Sustainable improvement of animal health care by systematic quality risk management according to the HACCP concept.

    Science.gov (United States)

    Noordhuizen, J P; Welpelo, H J

    1996-12-01

    This paper addresses the principles of the Hazard Analysis Critical Control Point (HACCP) concept as applied to animal health management strategy. Characteristics of the concept were analysed and compared with those of current animal health care strategies for disease risk identification and herd health management, insurance, and certification. HACCP is a hybrid strategy of quality control at both production process and product level. Animal health is considered a particular quality feature. We show that process control (expressed in terms of controlling both general and specific disease risk factors) and product control (expressed in terms of testing animals or animal products for specific disease agents) could form the basis for improving animal health. We conclude that HACCP provides ample opportunity for preventive health action and risk management at a relatively low cost in terms of labour, finance and documentation expenditure, at both the farm and sector level. Epidemiological field studies are currently needed to identify critical control points and to design HACCP procedures for livestock producers. In the long run, HACCP based animal health care can be further developed into a quality control systems approach to cover all aspects that are related, either directly or indirectly, to animal health.

  1. Chronic stress impacts the cardiovascular system: animal models and clinical outcomes.

    Science.gov (United States)

    Golbidi, Saeid; Frisbee, Jefferson C; Laher, Ismail

    2015-06-15

    Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies. Copyright © 2015 the American Physiological Society.

  2. Polycystic ovarian disease: animal models.

    Science.gov (United States)

    Mahajan, D K

    1988-12-01

    The reproductive systems of human beings and other vertebrates are grossly similar. In the ovary particularly, the biochemical and physiologic processes are identical not only in the formation of germ cells, the development of primordial follicles and their subsequent growth to Graafian follicles, and eventual ovulation but also in anatomic structure. In a noncarcinogenic human ovary, hypersecretion of androgen causes PCOD. Such hypersecretion may result from a nonpulsatile, constant elevated level of circulating LH or a disturbance in the action of neurotransmitters in the hypothalamus. In studying the pathophysiology of PCOD in humans, one must be aware of the limitations for manipulating the hypothalamic-pituitary axis. Although the rat is a polytocous rodent, the female has a regular ovarian cyclicity of 4 or 5 days, with distinct proestrus, estrus, and diestrus phases. Inasmuch as PCOD can be experimentally produced in the rat, that species is a good model for studying the pathophysiology of human PCOD. These PCOD models and their validity have been described: (1) estradiol-valerate, (2) DHA, (3) constant-light (LL), and (4) neonatally androgenized. Among these, the LL model is noninvasive and seems superior to the others for study of the pathophysiology of PCOD. The production of the polycystic ovarian condition in the rat by the injection of estrogens or androgens in neonate animals, or estradiol or DHA in adult rats, or the administration of antigonadotropins to these animals all cause a sudden appearance of the persistent estrus state by disturbing the metabolic and physiologic processes, whereas exposure of the adult rat to LL causes polycystic ovaries gradually, similar to what is seen in human idiopathic PCOD. After about 50 days of LL, the rat becomes anovulatory and the ovaries contain thickened tunica albuginea and many atretic follicles, and the tertiary follicles are considerably distended and cystic. The granulosa and theca cells appear normal

  3. The influence of feeding GMO-peas on growth of animal models

    Directory of Open Access Journals (Sweden)

    Petr Mares

    2014-02-01

    Full Text Available Introduction of genetically modified (GM food or feed into the commercial sale represents a very complicated process. One of the most important steps in approval process is the evaluation of all risks on the health status of people and animal models. Within our project the genetically modified peas was breeded that showed significant resistance against Pea seed-borne mosaic virus and Pea enation mosaic virus. Preclinical studies have been conducted to found out the effect of GMO peas on animals - rats of outbreeding line Wistar. In a total, 24 male, specific pathogen free Wistar rats were used in the experiment. At the beginning of the experiment, the animals were 28 days old. The three experimental groups with 8 individuals were created. The first group of rats was fed with GMO peas, the second group of rats consumed mix of pea cultivar Raman and the third group was control without pea addition (wheat and soya were used instead of pea. In the present study we focused our attention on health, growth and utility features of rats fed with GM pea. All characteristic were observed during the experiment lasting 35 days. Consumed feed was weighted daily and the weight of the animals was measured every seven days. The average values were compared within the groups. The aim of the experiment was to verify if resistant lines of pea influence the weight growth of animal models. The results of our experiment showed that even a high concentration (30% of GM pea did not influence growth rate of rats to compare with both rats fed with pea of Raman cultivar and control group. We did not observe any health problems of animal models during the experiment.

  4. Experimental psychiatric illness and drug abuse models: from human to animal, an overview.

    Science.gov (United States)

    Edwards, Scott; Koob, George F

    2012-01-01

    Preclinical animal models have supported much of the recent rapid expansion of neuroscience research and have facilitated critical discoveries that undoubtedly benefit patients suffering from psychiatric disorders. This overview serves as an introduction for the following chapters describing both in vivo and in vitro preclinical models of psychiatric disease components and briefly describes models related to drug dependence and affective disorders. Although there are no perfect animal models of any psychiatric disorder, models do exist for many elements of each disease state or stage. In many cases, the development of certain models is essentially restricted to the human clinical laboratory domain for the purpose of maximizing validity, whereas the use of in vitro models may best represent an adjunctive, well-controlled means to model specific signaling mechanisms associated with psychiatric disease states. The data generated by preclinical models are only as valid as the model itself, and the development and refinement of animal models for human psychiatric disorders continues to be an important challenge. Collaborative relationships between basic neuroscience and clinical modeling could greatly benefit the development of new and better models, in addition to facilitating medications development.

  5. Recent Advances in Translational Magnetic Resonance Imaging in Animal Models of Stress and Depression.

    Science.gov (United States)

    McIntosh, Allison L; Gormley, Shane; Tozzi, Leonardo; Frodl, Thomas; Harkin, Andrew

    2017-01-01

    Magnetic resonance imaging (MRI) is a valuable translational tool that can be used to investigate alterations in brain structure and function in both patients and animal models of disease. Regional changes in brain structure, functional connectivity, and metabolite concentrations have been reported in depressed patients, giving insight into the networks and brain regions involved, however preclinical models are less well characterized. The development of more effective treatments depends upon animal models that best translate to the human condition and animal models may be exploited to assess the molecular and cellular alterations that accompany neuroimaging changes. Recent advances in preclinical imaging have facilitated significant developments within the field, particularly relating to high resolution structural imaging and resting-state functional imaging which are emerging techniques in clinical research. This review aims to bring together the current literature on preclinical neuroimaging in animal models of stress and depression, highlighting promising avenues of research toward understanding the pathological basis of this hugely prevalent disorder.

  6. Recent Advances in Translational Magnetic Resonance Imaging in Animal Models of Stress and Depression

    Directory of Open Access Journals (Sweden)

    Allison L. McIntosh

    2017-05-01

    Full Text Available Magnetic resonance imaging (MRI is a valuable translational tool that can be used to investigate alterations in brain structure and function in both patients and animal models of disease. Regional changes in brain structure, functional connectivity, and metabolite concentrations have been reported in depressed patients, giving insight into the networks and brain regions involved, however preclinical models are less well characterized. The development of more effective treatments depends upon animal models that best translate to the human condition and animal models may be exploited to assess the molecular and cellular alterations that accompany neuroimaging changes. Recent advances in preclinical imaging have facilitated significant developments within the field, particularly relating to high resolution structural imaging and resting-state functional imaging which are emerging techniques in clinical research. This review aims to bring together the current literature on preclinical neuroimaging in animal models of stress and depression, highlighting promising avenues of research toward understanding the pathological basis of this hugely prevalent disorder.

  7. Comparison between a sire model and an animal model for genetic evaluation of fertility traits in Danish Holstein population

    DEFF Research Database (Denmark)

    Sun, C; Madsen, P; Nielsen, U S

    2009-01-01

    Comparisons between a sire model, a sire-dam model, and an animal model were carried out to evaluate the ability of the models to predict breeding values of fertility traits, based on data including 471,742 records from the first lactation of Danish Holstein cows, covering insemination years from...... the results suggest that the animal model, rather than the sire model, should be used for genetic evaluation of fertility traits......Comparisons between a sire model, a sire-dam model, and an animal model were carried out to evaluate the ability of the models to predict breeding values of fertility traits, based on data including 471,742 records from the first lactation of Danish Holstein cows, covering insemination years from...... 1995 to 2004. The traits in the analysis were days from calving to first insemination, calving interval, days open, days from first to last insemination, number of inseminations per conception, and nonreturn rate within 56 d after first service. The correlations between sire estimated breeding value...

  8. Preparation of recombinant proteins in milk to improve human and animal health

    OpenAIRE

    Soler , Eric; Thépot , Dominique; Rival-Gervier , Sylvie; JOLIVET , Geneviève; Houdebine , Louis-Marie

    2006-01-01

    International audience; Milk is a very abundant source of proteins for animal and human consumption. Milk composition can be modified using transgenesis, including exogenous gene addition and endogenous gene inactivation. The study of milk protein genes has provided researchers with regulatory regions capable of efficiently and specifically driving the expression of foreign genes in milk. The projects underway are aimed at modifying milk composition, improving its nutritional value, reducing ...

  9. Gender Differences in Animal Models of Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Hagit Cohen

    2011-01-01

    Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.

  10. Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection.

    Science.gov (United States)

    Yun, Nadezhda E; Ronca, Shannon; Tamura, Atsushi; Koma, Takaaki; Seregin, Alexey V; Dineley, Kelly T; Miller, Milagros; Cook, Rebecca; Shimizu, Naoki; Walker, Aida G; Smith, Jeanon N; Fair, Joseph N; Wauquier, Nadia; Bockarie, Bayon; Khan, Sheik Humarr; Makishima, Tomoko; Paessler, Slobodan

    2015-12-30

    Approximately one-third of Lassa virus (LASV)-infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa fever (LF), LASV is a major cause of hearing loss in regions of West Africa where LF is endemic. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent, while the virus isolated from a nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss. Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment. Copyright © 2016, American Society for Microbiology. All Rights

  11. Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them.

    Science.gov (United States)

    Chavatte-Palmer, Pascale; Tarrade, Anne; Rousseau-Ralliard, Delphine

    2016-06-14

    This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition) plays a seminal role in determining the offspring's long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD). In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta) or physical (ovine maternal and lamb birth weight) resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA) balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to propose

  12. Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them

    Directory of Open Access Journals (Sweden)

    Pascale Chavatte-Palmer

    2016-06-01

    Full Text Available This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition plays a seminal role in determining the offspring’s long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD. In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta or physical (ovine maternal and lamb birth weight resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to

  13. Estrogen agonist genistein differentially influences the cognitive and motor disorders in an ovariectomized animal model of Parkinsonism

    Directory of Open Access Journals (Sweden)

    Elaheh Arbabi

    2016-12-01

    Full Text Available Objective(s: Parkinson's disease (PD is a progressive neurological disorder associated with motor disabilities and cognitive dysfunction as well. Evidence indicates that PD occurs less frequently in women than men, confirming a role for steroid hormones in protection of dopaminergic nigrostriatal neurons. It is reported that soy genistein, an estrogen agonist phytoestrogen, display neuroprotective effects against neuronal death. In this study we evaluated the effect of genistein in animal models of Parkinsonism (P and Parkinsonism + ovariectomized (OP. Materials and Methods: The experiments were carried out on the control, P and OP animals. Learning and memory abilities were evaluated using Morris water maze. The latency and speed of locating the platform were measured as cognitive indices. Motor behaviors were assessed by testing the animals in rota rod and the latency to fall from the rod was scored. Results: We found that Parkinsonism leads to the cognitive and motor disabilities; ovariectomy intensified these disorders. Whereas genistein treatment improved the maze performances in both P and OP animals it failed to influence the kinetic problems. Genistein displayed a neuroprotective effect on dopaminergic neurons. Conclusion: Positive impact of genistein on the spatial learning and memory may reflect its effects on the nigrostriatal pathway and striatum. Nevertheless, ineffectiveness of genistein on the motor disorders, despite its neuroprotective impacts, led us to conclude that the cognitive improvement by genistein may also contribute to its effects in other areas of brain.

  14. Criticizing animal experimentation, at my peril.

    Science.gov (United States)

    Eisenman, Stephen F

    2016-01-01

    Initiatives leading to even modest reduction in animal use at major U.S. universities are likely to continue to face strong opposition. At least, that's the conclusion the author draws from his efforts at Northwestern University. In fact, despite a growing body of evidence that animal-based research is flawed at best and misleading or un-scientific at worst its use is growing at Northwestern and elsewhere. Moreover, recent discoveries concerning animal consciousness and emotion have not led to notable improvements in the conditions in which AWA protected animals live at the Chicago vivarium. There, animals languish in featureless rooms or sterile cages without access to daylight and with little opportunity to express their natural behaviors and aptitudes. The writer's public exposure of these conditions led to a fierce backlash. Unless there is a significant change in laboratory and university culture, change will only come when the marketplace and funding agencies demand better and more reliable, non-animal models for the testing of drug toxicity and effectiveness.

  15. The establishment of animal model of acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

    2008-01-01

    Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

  16. Animal models as tools to study the pathophysiology of depression

    Directory of Open Access Journals (Sweden)

    Helena M. Abelaira

    2013-01-01

    Full Text Available The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

  17. Social Stress in Rats : An Animal Model of Depression?

    NARCIS (Netherlands)

    Koolhaas, J.M.; Meerlo, P.; De Boer, S..; Strubbe, J.H.; Bohus, B.

    1995-01-01

    Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches

  18. Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.

    Science.gov (United States)

    Offiah, Ifeoma; Didangelos, Athanasios; OʼReilly, Barry A; McMahon, Stephen B

    2017-01-01

    Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.

  19. Development an Automatic Speech to Facial Animation Conversion for Improve Deaf Lives

    Directory of Open Access Journals (Sweden)

    S. Hamidreza Kasaei

    2011-05-01

    Full Text Available In this paper, we propose design and initial implementation of a robust system which can automatically translates voice into text and text to sign language animations. Sign Language
    Translation Systems could significantly improve deaf lives especially in communications, exchange of information and employment of machine for translation conversations from one language to another has. Therefore, considering these points, it seems necessary to study the speech recognition. Usually, the voice recognition algorithms address three major challenges. The first is extracting feature form speech and the second is when limited sound gallery are available for recognition, and the final challenge is to improve speaker dependent to speaker independent voice recognition. Extracting feature form speech is an important stage in our method. Different procedures are available for extracting feature form speech. One of the commonest of which used in speech
    recognition systems is Mel-Frequency Cepstral Coefficients (MFCCs. The algorithm starts with preprocessing and signal conditioning. Next extracting feature form speech using Cepstral coefficients will be done. Then the result of this process sends to segmentation part. Finally recognition part recognizes the words and then converting word recognized to facial animation. The project is still in progress and some new interesting methods are described in the current report.

  20. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2016-09-01

    Full Text Available Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found. For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies was assessed and outcome data were collected for meta-analysis (151 studies. Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0–100% scale. Implantation of acellular

  1. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; van Kuppevelt, Toin H; de Vries, Rob B M; Daamen, Willeke F

    2016-01-01

    Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly

  2. Hepatoprotective activity of Musa paradisiaca on experimental animal models.

    Science.gov (United States)

    Nirmala, M; Girija, K; Lakshman, K; Divya, T

    2012-01-01

    To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

  3. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones.

    Science.gov (United States)

    Nuss, Katja M R; Auer, Joerg A; Boos, Alois; von Rechenberg, Brigitte

    2006-08-15

    The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

  4. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    Directory of Open Access Journals (Sweden)

    Boos Alois

    2006-08-01

    Full Text Available Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

  5. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    Science.gov (United States)

    Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

    2006-01-01

    Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials. PMID:16911787

  6. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

    Directory of Open Access Journals (Sweden)

    Chang RB

    2015-04-01

    Full Text Available Renbao Chang,1 Xudong Liu,1 Shihua Li,2 Xiao-Jiang Li1,2 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Abstract: Huntington’s disease (HD is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. Keywords: transgenic animal models, Huntington’s disease, pathogenesis, therapy

  7. Improving accuracy of genomic prediction in Brangus cattle by adding animals with imputed low-density SNP genotypes.

    Science.gov (United States)

    Lopes, F B; Wu, X-L; Li, H; Xu, J; Perkins, T; Genho, J; Ferretti, R; Tait, R G; Bauck, S; Rosa, G J M

    2018-02-01

    Reliable genomic prediction of breeding values for quantitative traits requires the availability of sufficient number of animals with genotypes and phenotypes in the training set. As of 31 October 2016, there were 3,797 Brangus animals with genotypes and phenotypes. These Brangus animals were genotyped using different commercial SNP chips. Of them, the largest group consisted of 1,535 animals genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to the SNP content of the GGP-LDV4 chip, so that the number of animals available for training the genomic prediction models was more than doubled. The present study showed that the pooling of animals with both original or imputed 40K SNP genotypes substantially increased genomic prediction accuracies on the ten traits. By supplementing imputed genotypes, the relative gains in genomic prediction accuracies on estimated breeding values (EBV) were from 12.60% to 31.27%, and the relative gain in genomic prediction accuracies on de-regressed EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the performance of five genomic prediction models and two cross-validation methods. The five genomic models predicted EBV and de-regressed EBV of the ten traits similarly well. Of the two cross-validation methods, leave-one-out cross-validation maximized the number of animals at the stage of training for genomic prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was validated in 1,106 newly genotyped Brangus animals based on the SNP effects estimated in the previous set of 3,797 Brangus animals, and they were slightly lower than GPA in the original data. The present study was the first to leverage currently available genotype and phenotype resources in order to harness genomic prediction in Brangus beef cattle. © 2018 Blackwell Verlag GmbH.

  8. Animal models of gene-environment interactions in schizophrenia.

    Science.gov (United States)

    Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V

    2009-12-07

    The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.

  9. Zebrafish: an animal model for research in veterinary medicine.

    Science.gov (United States)

    Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J

    2015-01-01

    The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic

  10. Animal Transports

    Directory of Open Access Journals (Sweden)

    Diana Ludrovcová

    2016-08-01

    Full Text Available Purpose and Originality: The research is aimed to the animal transports issue, from two points of view – first is the animal cruelty and second is the policy and economic consideration. The goal is to acquaint the readers with the transports risks and its cruelty and evaluation of the economic, political aspects for he involved countries. The study is oriented on more points of view, what is rare in works with a similar theme. Method: This paper examines many issues and examinations from different authors and subsequently summarized the findings with authors own knowledge to one expanded unit. Results: Results proves, that livestock transports have negative impact on animal´s health, environment. Number of transported animals is rising every year. Society: Research familiarize the society with the animal transports, cruelty against animals during them, and influence of transports on some countries, their economy, policy. People get better informed and can form their own opinion on this topic. They may start acting, undertaking some steps to improve the present situation, what could help a lot to animals and environment. Limitations / further research: Future research could show progress and improvement of transports, quality of food supply and economics.

  11. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    James G. McLarnon

    2014-01-01

    Full Text Available Animal models of Alzheimer’s disease (AD which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid-β (Aβ into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

  12. Animal rights, animal minds, and human mindreading.

    Science.gov (United States)

    Mameli, M; Bortolotti, L

    2006-02-01

    Do non-human animals have rights? The answer to this question depends on whether animals have morally relevant mental properties. Mindreading is the human activity of ascribing mental states to other organisms. Current knowledge about the evolution and cognitive structure of mindreading indicates that human ascriptions of mental states to non-human animals are very inaccurate. The accuracy of human mindreading can be improved with the help of scientific studies of animal minds. However, the scientific studies do not by themselves solve the problem of how to map psychological similarities (and differences) between humans and animals onto a distinction between morally relevant and morally irrelevant mental properties. The current limitations of human mindreading-whether scientifically aided or not-have practical consequences for the rational justification of claims about which rights (if any) non-human animals should be accorded.

  13. Genetic and non-genetic animal models for autism spectrum disorders (ASD).

    Science.gov (United States)

    Ergaz, Zivanit; Weinstein-Fudim, Liza; Ornoy, Asher

    2016-09-01

    Autism spectrum disorder (ASD) is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal and postnatal etiologies. We discuss the known animal models, mostly in mice and rats, of ASD that helps us to understand the etiology, pathogenesis and treatment of human ASD. We describe only models where behavioral testing has shown autistic like behaviors. Some genetic models mimic known human syndromes like fragile X where ASD is part of the clinical picture, and others are without defined human syndromes. Among the environmentally induced ASD models in rodents, the most common model is the one induced by valproic acid (VPA) either prenatally or early postnatally. VPA induces autism-like behaviors following single exposure during different phases of brain development, implying that the mechanism of action is via a general biological mechanism like epigenetic changes. Maternal infection and inflammation are also associated with ASD in man and animal models. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. A knowledge based approach to matching human neurodegenerative disease and animal models

    Directory of Open Access Journals (Sweden)

    Maryann E Martone

    2013-05-01

    Full Text Available Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have explored the use of ontologies to create formal descriptions of structural phenotypes across scales that are machine processable and amenable to logical inference. As proof of concept, we built a Neurodegenerative Disease Phenotype Ontology and an associated Phenotype Knowledge Base using an entity-quality model that incorporates descriptions for both human disease phenotypes and those of animal models. Entities are drawn from community ontologies made available through the Neuroscience Information Framework and qualities are drawn from the Phenotype and Trait Ontology. We generated ~1200 structured phenotype statements describing structural alterations at the subcellular, cellular and gross anatomical levels observed in 11 human neurodegenerative conditions and associated animal models. PhenoSim, an open source tool for comparing phenotypes, was used to issue a series of competency questions to compare individual phenotypes among organisms and to determine which animal models recapitulate phenotypic aspects of the human disease in aggregate. Overall, the system was able to use relationships within the ontology to bridge phenotypes across scales, returning non-trivial matches based on common subsumers that were meaningful to a neuroscientist with an advanced knowledge of neuroanatomy. The system can be used both to compare individual phenotypes and also phenotypes in aggregate. This proof of concept suggests that expressing complex phenotypes using formal

  15. Towards an animal model of callousness.

    Science.gov (United States)

    Hernandez-Lallement, Julen; van Wingerden, Marijn; Kalenscher, Tobias

    2016-12-28

    Callous-unemotional traits - the insensitivity to other's welfare and well-being - are characterized by a lack of empathy. They are characteristic of psychopathy and can be found in other anti-social disorders, such as conduct disorder. Because of the increasing prevalence of anti-social disorders and the rising societal costs of violence and aggression, it is of great importance to elucidate the psychological and physiological mechanisms underlying callousness in the search for pharmacological treatments. One promising avenue is to create a relevant animal model to explore the neural bases of callousness. Here, we review recent advances in rodent models of pro-social choice that could be applied to probe the absence of pro-sociality as a proxy of callous behavior, and provide future directions for the exploration of the neural substrates of callousness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Development of computational small animal models and their applications in preclinical imaging and therapy research.

    Science.gov (United States)

    Xie, Tianwu; Zaidi, Habib

    2016-01-01

    The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future.

  17. Development of computational small animal models and their applications in preclinical imaging and therapy research

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Tianwu [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva 4 CH-1211 (Switzerland); Zaidi, Habib, E-mail: habib.zaidi@hcuge.ch [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva 4 CH-1211 (Switzerland); Geneva Neuroscience Center, Geneva University, Geneva CH-1205 (Switzerland); Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9700 RB (Netherlands)

    2016-01-15

    The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future.

  18. Development of computational small animal models and their applications in preclinical imaging and therapy research

    International Nuclear Information System (INIS)

    Xie, Tianwu; Zaidi, Habib

    2016-01-01

    The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future

  19. Modelling nitrogen and carbon interactions in composting of animal manure in naturally aerated piles.

    Science.gov (United States)

    Oudart, D; Robin, P; Paillat, J M; Paul, E

    2015-12-01

    Composting animal manure with natural aeration is a low-cost and low-energy process that can improve nitrogen recycling in millions of farms world-wide. Modelling can decrease the cost of choosing the best options for solid manure management in order to decrease the risk of loss of fertilizer value and ammonia emission. Semi-empirical models are suitable, considering the scarce data available in farm situations. Eleven static piles of pig or poultry manure were monitored to identify the main processes governing nitrogen transformations and losses. A new model was implemented to represent these processes in a pile considered as homogeneous. The model is based on four modules: biodegradation, nitrogen transformations and volatilization, thermal exchanges, and free air space evolution. When necessary, the parameters were calibrated with the data set. The results showed that microbial growth could reduce ammonia volatilization. Greatest nitrogen conservation is achieved when microbial growth was limited by nitrogen availability. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. How does sex matter? Behavior, stress and animal models of neurobehavioral disorders.

    Science.gov (United States)

    Palanza, Paola; Parmigiani, Stefano

    2017-05-01

    Many aspects of brain functioning exhibit important sex differences that affect behavior, mental health and mental disorders. However, most translational neuroscience research related to animal models of neurobehavioral disorders are carried out in male animals only. Based on published data from our laboratory on the House mouse, we discuss the following issues: (1) sex differences in social behavior of wild-derived mice; (2) artificial selection of laboratory strains and its consequences on social and reproductive competition; (3) sex-dependent effects of common experimental procedures; (4) differential effects of developmental events: the case of endocrine disruption; (5) implications for female models of stress and neurobehavioral disorders. Altogether, this review of data outline the marked differences of male and female responses to different social challenges and evinces the current lack of a relevant female mouse model of social stress. Whilst animal modelling is an important approach towards understanding mechanisms of neurobehavioral disorders, it is evident that data obtained in males may be irrelevant for inferring psychopathology and efficacy of pharmacological treatments for females. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Animal models of social stress: the dark side of social interactions.

    Science.gov (United States)

    Masis-Calvo, Marianela; Schmidtner, Anna K; de Moura Oliveira, Vinícius E; Grossmann, Cindy P; de Jong, Trynke R; Neumann, Inga D

    2018-05-10

    Social stress occurs in all social species, including humans, and shape both mental health and future interactions with conspecifics. Animal models of social stress are used to unravel the precise role of the main stress system - the HPA axis - on the one hand, and the social behavior network on the other, as these are intricately interwoven. The present review aims to summarize the insights gained from three highly useful and clinically relevant animal models of psychosocial stress: the resident-intruder (RI) test, the chronic subordinate colony housing (CSC), and the social fear conditioning (SFC). Each model brings its own focus: the role of the HPA axis in shaping acute social confrontations (RI test), the physiological and behavioral impairments resulting from chronic exposure to negative social experiences (CSC), and the neurobiology underlying social fear and its effects on future social interactions (SFC). Moreover, these models are discussed with special attention to the HPA axis and the neuropeptides vasopressin and oxytocin, which are important messengers in the stress system, in emotion regulation, as well as in the social behavior network. It appears that both nonapeptides balance the relative strength of the stress response, and simultaneously predispose the animal to positive or negative social interactions.

  2. Contribution of nonprimate animal models in understanding the etiology of schizophrenia

    Science.gov (United States)

    Lazar, Noah L.; Neufeld, Richard W.J.; Cain, Donald P.

    2011-01-01

    Schizophrenia is a severe psychiatric disorder that is characterized by positive and negative symptoms and cognitive impairments. The etiology of the disorder is complex, and it is thought to follow a multifactorial threshold model of inheritance with genetic and neurodevelopmental contributions to risk. Human studies are particularly useful in capturing the richness of the phenotype, but they are often limited to the use of correlational approaches. By assessing behavioural abnormalities in both humans and rodents, nonprimate animal models of schizophrenia provide unique insight into the etiology and mechanisms of the disorder. This review discusses the phenomenology and etiology of schizophrenia and the contribution of current nonprimate animal models with an emphasis on how research with models of neurotransmitter dysregulation, environmental risk factors, neurodevelopmental disruption and genetic risk factors can complement the literature on schizophrenia in humans. PMID:21247514

  3. Gaps in US Animal Welfare Law for Laboratory Animals: Perspectives From an Animal Law Attorney.

    Science.gov (United States)

    Frasch, Pamela D

    2016-05-01

    The use of animals in biomedical, toxicological, and basic research has been common practice, and a tool for scientists and researchers, for many years. And yet, serious conflict continues to exist between those who believe that the use of animals in research will yield scientific results that benefit humans and those who believe such practices are unethical regardless of use or outcome. High-profile undercover cases have further raised public awareness and have put the entire industry under pressure to be transparent, accountable, and aggressive in its adoption of reduction, refinement, and replacement (3R) principles. Many animal law attorneys are deeply frustrated by what they see as weak US laws that are unevenly enforced, especially when compared with legal advances in other countries and regions. This article (1) explores those gaps in US animal welfare laws with an emphasis on the Animal Welfare Act, (2) argues in favor of stronger laws and rigorous enforcement, and (3) suggests steps to advance these goals. These steps include (1) expanding the definition of "animal" in the Animal Welfare Act (AWA), (2) improving and expanding minimum care requirements in USDA regulations, (3) instituting mandatory reporting requirements, improving Institutional Animal Care and Use Committees, and allowing easier accessibility to laboratory reports and plans, (4) adding a citizen suit provision to the AWA, and (5) continuing education about the emotional and social capacities of animals and a stronger commitment to 3R principles. © The Author 2017. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.