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Sample records for relevant animal model

  1. The relevance of animal models in osteoarthritis.

    PubMed

    Moskowitz, R W

    1990-01-01

    Studies of osteoarthritis (OA) in humans are restricted by the slow rate at which the disease progresses, and the limited opportunity for study of the tissue changes over time. A range of animal models of OA have been developed which demonstrate histopathological and gross features typical of OA in humans. Animal models can be used to study OA, and to investigate the effects of a variety of agents, including so-called chondroprotective agents, on the progression of the disease.

  2. Are animal models relevant to key aspects of human parturition?

    PubMed

    Mitchell, Bryan F; Taggart, Michael J

    2009-09-01

    Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are

  3. Animal models of alcoholic liver disease: Pathogenesis and clinical relevance.

    PubMed

    Gao, Bin; Xu, Ming-Jiang; Bertola, Adeline; Wang, Hua; Zhou, Zhou; Liangpunsakul, Suthat

    2017-04-14

    Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and test therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.

  4. Relevance of animal models to human tardive dyskinesia

    PubMed Central

    2012-01-01

    Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia. PMID:22404856

  5. Relevance of pharmacokinetic parameters in animal models of methamphetamine abuse.

    PubMed

    Cho, A K; Melega, W P; Kuczenski, R; Segal, D S

    2001-02-01

    Although the behavioral consequences of methamphetamine (METH) abuse have been extensively documented, a more precise and thorough understanding of underlying neurobiological mechanisms still requires the use of animal models. To study these biochemical processes in experimental animals requires consideration for the broad range of human METH abuse patterns and the many factors that have been identified to profoundly influence the behavioral and neurochemical effects of exposure to METH-like stimulants. One potentially critical issue relates to pharmacokinetic differences between the species. In this review, METH plasma pharmacokinetic profiles after single and multiple dose intravenous METH administration are compared for the rat and human. Significant differences in elimination half-life between the two species (t1/2: rat-70 min, human-12 h) result in markedly dissimilar profiles of METH exposure. However, the plasma profile of a human METH binge pattern can be approximated in the rat by increasing METH dose frequency. Consideration of METH pharmacokinetics in animal models should permit a closer simulation of the temporal profile of METH exposure in the human CNS and should provide further insight into the mechanisms contributing to the addiciton and psychopathology associated with METH abuse.

  6. Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges.

    PubMed

    Greenwood-Van Meerveld, Beverley; Prusator, Dawn K; Johnson, Anthony C

    2015-06-01

    Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal organs. In contrast to somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. Animal models have played a pivotal role in our understanding of the mechanisms underlying the pathophysiology of visceral pain. This review focuses on animal models of visceral pain and their translational relevance. In addition, the challenges of using animal models to develop novel therapeutic approaches to treat visceral pain will be discussed. Copyright © 2015 the American Physiological Society.

  7. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    PubMed

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  8. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges

    PubMed Central

    Ney, Denise M.; Sigalet, David L.; Vegge, Andreas; Burrin, Douglas

    2014-01-01

    Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing 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, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the

  9. Translational Relevance and Recent Advances of Animal Models of Abdominal Aortic Aneurysm.

    PubMed

    Sénémaud, Jean; Caligiuri, Giuseppina; Etienne, Harry; Delbosc, Sandrine; Michel, Jean-Baptiste; Coscas, Raphaël

    2017-03-01

    Human abdominal aortic aneurysm (AAA) pathophysiology is not yet completely understood. In conductance arteries, the insoluble extracellular matrix, synthesized by vascular smooth muscle cells, assumes the function of withstanding the intraluminal arterial blood pressure. Progressive loss of this function through extracellular matrix proteolysis is a main feature of AAAs. As most patients are now treated via endovascular approaches, surgical AAA specimens have become rare. Animal models provide valuable complementary insights into AAA pathophysiology. Current experimental AAA models involve induction of intraluminal dilation (nondissecting AAAs) or a contained intramural rupture (dissecting models). Although the ideal model should reproduce the histological characteristics and natural history of the human disease, none of the currently available animal models perfectly do so. Experimental models try to represent the main pathophysiological determinants of AAAs: genetic or acquired defects in extracellular matrix, loss of vascular smooth muscle cells, and innate or adaptive immune response. Nevertheless, most models are characterized by aneurysmal stabilization and healing after a few weeks because of cessation of the initial stimulus. Recent studies have focused on ways to optimize existing models to allow continuous aneurysmal growth. This review aims to discuss the relevance and recent advances of current animal AAA models. An online visual overview is available for this article. © 2017 American Heart Association, Inc.

  10. Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

    PubMed

    Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

    2013-01-01

    Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials.

  11. [Relevance of animal models in the study of human pathologies: a mouse model of Down syndrome].

    PubMed

    Morice, Elise

    2010-01-01

    Animal models provide a simplified representation of biological systems impossible to study directly in the human being. Regarding genetic pathologies, mouse models are the most studied since they enable to reproduce in animals the mutation of the gene or genes responsible for the disease and to study the phenotypic consequences. Down syndrome is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21) and is characterized by different degrees of phenotypic alterations including morphological, cardiac, muscular, cerebral, motor and intellectual changes. This high phenotypic heterogeneity involves genetic and environmental effects, which are impossible to dissect out in human beings. Various models in mice have been developed in order to identify the genetic and neurobiological mechanisms responsible for Down syndrome. The Tc1 mouse is the most complete genetic animal model currently available to study Down syndrome, since it carries an almost complete Hsa 21. The behavioural and electrophysiological studies of this model reveal a great similarity between the animal phenotype and the Down syndrome symptomatology, consequently this model represents a powerful genetic tool with a potential to unravel the mechanisms underlying the deficiencies array characteristic of this human condition. In the long term, Tc1 mice will contribute to the development and the screening of new therapeutics, with the goal of improving all the impairments reported in Down syndrome.

  12. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

    PubMed Central

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

  13. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges.

    PubMed

    Lu, Peng; Sodhi, Chhinder P; Jia, Hongpeng; Shaffiey, Shahab; Good, Misty; Branca, Maria F; Hackam, David J

    2014-06-01

    Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored.

  14. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges

    PubMed Central

    Lu, Peng; Sodhi, Chhinder P.; Jia, Hongpeng; Shaffiey, Shahab; Good, Misty; Branca, Maria F.

    2014-01-01

    Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored. PMID:24763555

  15. Opportunities and challenges in developing relevant animal models for Alzheimer's disease.

    PubMed

    De Felice, Fernanda G; Munoz, Douglas P

    2016-03-01

    A major impediment to the development of safe and effective therapeutics in Alzheimer's disease (AD) lies in difficulties in translating research findings across species: therapies that work in rodents often do not translate to humans. A route to bridge the gap between promising rodent research and the human clinical condition consists in using non-human primates (NHPs), which are phylogenetically much closer to humans. In this article, we discuss the importance of investigating disease mechanisms from cell culture, through different animal models of disease. We highlight that developing a viable, validated NHP AD model will likely be a key step toward understanding AD-relevant pathogenic mechanisms and for developing therapies that will effectively translate to the human disease condition. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

    PubMed

    Swerdlow, Neal R; Light, Gregory A

    Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct levels for schizophrenia therapeutics, neurophysiological endophenotypes, and potential causative insults for this group of disorders. However, with the growing recognition of the heterogeneity of the schizophrenias, and the less sanguine view of the clinical value of antipsychotic (AP) medications, our field must look beyond "validity," to assess the actual utility of these models. At a substantial cost in terms of research support and intellectual capital, what has come from these models, that we can say has actually helped schizophrenia patients? Such introspection is timely, as we are reassessing not only our view of the genetic and pathophysiological diversity of these disorders, but also the predominant strategies for SZ therapeutics; indeed, our field is gaining awareness that we must move away from a "find what's broke and fix it" approach, toward identifying spared neural and cognitive function in SZ patients, and matching these residual neural assets with learning-based therapies. Perhaps, construct-valid models that identify evidence of "spared function" in neural substrates might reveal opportunities for future therapeutics and allow us to study these substrates at a mechanistic level to maximize opportunities for neuroplasticity. Such an effort will require a retooling of our models, and more importantly, a re-evaluation of their utility. For animal models to remain relevant in the search for schizophrenia therapeutics, they will need to focus less on what is valid and focus more on what is useful.

  17. Multiple system organ response induced by hyperoxia in a clinically relevant animal model of sepsis.

    PubMed

    Rodríguez-González, Raquel; Martín-Barrasa, José Luis; Ramos-Nuez, Ángela; Cañas-Pedrosa, Ana María; Martínez-Saavedra, María Teresa; García-Bello, Miguel Ángel; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Slutsky, Arthur S; Villar, Jesús

    2014-08-01

    Oxygen therapy is currently used as a supportive treatment in septic patients to improve tissue oxygenation. However, oxygen can exert deleterious effects on the inflammatory response triggered by infection. We postulated that the use of high oxygen concentrations may be partially responsible for the worsening of sepsis-induced multiple system organ dysfunction in an experimental clinically relevant model of sepsis. We used Sprague-Dawley rats. Sepsis was induced by cecal ligation and puncture. Sham-septic controls (n = 16) and septic animals (n = 32) were randomly assigned to four groups and placed in a sealed Plexiglas cage continuously flushed for 24 h with medical air (group 1), 40% oxygen (group 2), 60% oxygen (group 3), or 100% oxygen (group 4). We examined the effects of these oxygen concentrations on the spread of infection in blood, urine, peritoneal fluid, bronchoalveolar lavage, and meninges; serum levels of inflammatory biomarkers and reactive oxygen species production; and hematological parameters in all experimental groups. In cecal ligation and puncture animals, the use of higher oxygen concentrations was associated with a greater number of infected biological samples (P < 0.0001), higher serum levels of interleukin-6 (P < 0.0001), interleukin-10 (P = 0.033), and tumor necrosis factor-α (P = 0.034), a marked decrease in platelet counts (P < 0.001), and a marked elevation of reactive oxygen species serum levels (P = 0.0006) after 24 h of oxygen exposure. Oxygen therapy greatly influences the progression and clinical manifestation of multiple system organ dysfunction in experimental sepsis. If these results are extrapolated to humans, they suggest that oxygen therapy should be carefully managed in septic patients to minimize its deleterious effects.

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

    PubMed

    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.

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

    PubMed Central

    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

  20. How Relevant Are Imaging Findings in Animal Models of Movement Disorders to Human Disease?

    PubMed

    Bannon, Darryl; Landau, Anne M; Doudet, Doris J

    2015-08-01

    The combination of novel imaging techniques with the use of small animal models of disease is often used in attempt to understand disease mechanisms, design potential clinical biomarkers and therapeutic interventions, and develop novel methods with translatability to human clinical conditions. However, it is clear that most animal models are deficient when compared to the complexity of human diseases: they cannot sufficiently replicate all the features of multisystem disorders. Furthermore, some practical differences may affect the use or interpretation of animal imaging to model human conditions such as the use of anesthesia, various species differences, and limitations of methodological tools. Nevertheless, imaging animal models allows us to dissect, in interpretable bits, the effects of one system upon another, the consequences of variable neuronal losses or overactive systems, the results of experimental treatments, and we can develop and validate new methods. In this review, we focus on imaging modalities that are easily used in both human subjects and animal models such as positron emission and magnetic resonance imaging and discuss aging and Parkinson's disease as prototypical examples of preclinical imaging studies.

  1. Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges.

    PubMed

    Mathews, Stephanie; Xu, Mingjiang; Wang, Hua; Bertola, Adeline; Gao, Bin

    2014-05-15

    Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

  2. A clinically relevant animal model of TMD and IBS co-morbidity

    PubMed Central

    Traub, Richard J.; Cao, Dong-Yuan; Karpowicz, Jane; Pandya, Sangeeta; Ji, Yaping; Dorsey, Susan G.; Dessem, Dean

    2014-01-01

    Temporomandibular disorders (TMD) and irritable bowel syndrome (IBS) are comorbid functional chronic pain disorders of unknown etiology that are triggered/exacerbated by stress. Here we present baseline phenotypic characterization of a novel animal model to gain insight into the underlying mechanisms that contribute to such comorbid pain conditions. In this model, chronic visceral hypersensitivity, a defining symptom of IBS, is dependent upon on three factors: estradiol, existing chronic somatic pain, and stress. In ovariectomized rats, estradiol replacement followed by craniofacial muscle injury and stress induced visceral hypersensitivity that persisted for months. Omission of any one factor resulted in a transient (1 week) visceral hypersensitivity from stress alone, or no hypersensitivity (no inflammation or estradiol). Maintenance of visceral hypersensitivity was estradiol dependent; resolving when estradiol replacement ceased. Referred cutaneous hypersensitivity was concurrent with visceral hypersensitivity. Increased spinal Fos expression suggests induction of central sensitization. These data demonstrate the development and maintenance of visceral hypersensitivity in estradiol-replaced animals following distal somatic injury and stress that mimics some characteristics reported in patients with TMD and comorbid IBS. This new animal model is a powerful experimental tool which can be employed to gain further mechanistic insight into overlapping pain conditions. PMID:24981128

  3. Congenital diaphragmatic hernia: comparison of animal models and relevance to the human situation.

    PubMed

    van Loenhout, Rhiannon B; Tibboel, Dick; Post, Martin; Keijzer, Richard

    2009-01-01

    Congenital diaphragmatic hernia (CDH) occurs in 1 in 3,000 newborns. Mortality and morbidity are due to the amount of pulmonary hypoplasia (PH), the response on artificial ventilation and the presence of therapy-resistant pulmonary hypertension. The pathogenesis and etiology of CDH and its associated anomalies are still largely unknown despite all research efforts over the past years. Several animal models have been proposed to study CDH. In this review we compare surgical, pharmacological and transgenic models, and discuss their strengths and limitations to study PH.

  4. Maintaining the clinical relevance of animal models in translational studies of post-traumatic stress disorder.

    PubMed

    Cohen, Hagit; Matar, Michael A; Zohar, Joseph

    2014-01-01

    The diagnosis of Post-Traumatic Stress Disorder (PTSD) is conditional on directly experiencing or witnessing a significantly threatening event and the presence of a certain minimal number of symptoms from each of four symptom clusters (re-experiencing, avoidance, negative cognition and mood, and hyperarousal) at least one month after the event (DSM 5) (American Psychiatric Association 2013). Only a proportion of the population exposed develops symptoms fulfilling the criteria. The individual heterogeneity in responses of stress-exposed animals suggested that adapting clearly defined and reliably reproducible "diagnostic", i.e. behavioral, criteria for animal responses would augment the clinical validity of the analysis of study data. We designed cut-off (inclusion/exclusion) behavioral criteria (CBC) which classify study subjects as being severely, minimally or partially affected by the stress paradigm, to be applied retrospectively in the analysis of behavioral data. Behavioral response classification enables the researcher to correlate (retrospectively) specific anatomic, bio-molecular and physiological parameters with the degree and pattern of the individual behavioral response, and also introduces "prevalence rates" as a valid study-parameter. The cumulative results of our studies indicate that, by classifying the data from individual subjects according to their response patterns, the animal study can more readily be translated into clinical "follow-up" studies and back again. This article will discuss the concept of the model and its background, and present a selection of studies employing and examining the model, alongside the underlying translational rationale of each. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. New insight into oseophageal injury and protection in physiologically relevant animal models.

    PubMed

    Zayachkivska, O; Pshyk-Titko, I; Hrycevych, N; Savytska, M

    2014-04-01

    Chronic diseases of lifestyle (CDL), the most common chronic group of non-infectious and non-transmissible diseases worldwide, which share the similar risk factors of unhealthy lifestyle, have become most recognized as a serious trigger in the genesis of oesophageal injury. Non-erosive oesophageal lesions (NEOL) are found more frequently than erosive or ulcer lesions in patients with reflux oesophagitis (RO) related to CDL. They also have restricted healing options, which often leads to carcinogenesis. Therefore, developing a physiologically relevant animal model of NEOL remains an urgent priority. One of triggers of CDL, postprandial hyperglycemia (PHG), which is characterized by hyperglycemic spikes, and overloading nitro-compounds leading to oxidative stress that may predispose to NEOL. The present study was designed to set up a model of RO related to CDL in rodents to understand mechanisms of oesophageal preulcerogenic injury under such conditions as food-associated long-term PHG, restrained water-immersion stress (WIS), and imbalance of entero-salivary nitrites recirculation (ESNR). Beneficial effects of L-tryptophan (L-Try) have already been described by many activities in kynurenine and melatonin (Mel) synthesis, redox reactions, which play a key role for cytoprotection and proliferation. Nevertheless, the effect of L-Try and Mel on NEOL under PHG is still unknown. An extract of Cucurbita maxim sweet seed (eCMS), which contains a high amount of antioxidants, also appear to play an important role in foregut cytoprotection. Thus, the second aim was to observe the effects of eCSE on oesophageal mucosa (OEM) in modification of ESNR (mESNR). Rats were used with without/with pre-treatment L-Try, Mel during WIS and PHG. In the second series of experiments rats were used with without/with CSE pre-treatment in mESNR; oral and OEM lesions were determined by histology; inflammation of OEM by lectin histochemistry; esophageal NO2(-), cNOS and iNOS via bioassays

  6. The relevance of individual genetic background and its role in animal models of epilepsy.

    PubMed

    Schauwecker, P Elyse

    2011-11-01

    Growing evidence has indicated that genetic factors contribute to the etiology of seizure disorders. Most epilepsies are multifactorial, involving a combination of additive and epistatic genetic variables. However, the genetic factors underlying epilepsy have remained unclear, partially due to epilepsy being a clinically and genetically heterogeneous syndrome. Similar to the human situation, genetic background also plays an important role in modulating both seizure susceptibility and its neuropathological consequences in animal models of epilepsy, which has too often been ignored or not been paid enough attention to in published studies. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. The purpose of this review is to discuss the effects of genetic background strain on epilepsy phenotypes of mice, to remind researchers that the background genetics of a knockout strain can have a profound influence on any observed phenotype, and outline the means by which to overcome potential genetic background effects in experimental models of epilepsy. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Genes and molecules that can potentiate or attenuate psychostimulant dependence: relevance of data from animal models to human addiction.

    PubMed

    Niwa, Minae; Yan, Yijin; Nabeshima, Toshitaka

    2008-10-01

    Recent evidence suggests that a variety of molecule products play critical roles in the transitions from recreational drug use to drug abuse, and then to drug dependence. Elucidation of the roles of specific molecules in the development of drug dependence can come from preclinical animal models and/or from clinical data. Among animal models, behavioral sensitization, conditioned place preference, drug discrimination, drug self-administration, and extensions of these basic procedures have been widely used to identify molecule products that might be involved in psychostimulant dependence. Repeated exposure to psychostimulants causes cellular adaptations in specific neuronal populations that are likely to contribute to dependence in some humans. In animal models, molecules that include shati, piccolo, tumor necrosis factor-alpha, and glial cell line-derived neurotrophic factor can act as antiaddictive factors. In some of these models, other molecules including matrix metalloproteinase and tissue plasminogen activator can act as proaddictive factors. We review evidence that the balance between levels of anti- and proaddictive factors induced by addictive drugs could play important roles in developing drug dependence. We focus on potential risk molecules in animal models for the development of methamphetamine dependence and their relevance to abusers. We propose that dynamic changes in the balance between levels of antiaddictive and proaddictive factors in the brain provide some of the determinants of susceptibility to drug dependence. Exploration of the roles that candidate molecules play in an appropriate repertoire of animal behavioral models, especially drug self-administration and extensions thereof, should thus help us to understand human stimulant dependence.

  8. Monitoring for potential adverse effects of prenatal gene therapy: use of large animal models with relevance to human application.

    PubMed

    Mehta, Vedanta; Abi-Nader, Khalil N; Carr, David; Wallace, Jacqueline; Coutelle, Charles; Waddington, Simon N; Peebles, Donald; David, Anna L

    2012-01-01

    Safety is an absolute prerequisite for introducing any new therapy, and the need to monitor the consequences of administration of both vector and transgene to the fetus is particularly important. The unique features of fetal development that make it an attractive target for gene therapy, such as its immature immune system and rapidly dividing populations of stem cells, also mean that small perturbations in pregnancy can have significant short- and long-term consequences. Certain features of the viral vectors used, the product of the delivered gene, and sometimes the invasive techniques necessary to deliver the construct to the fetus in utero have the potential to do harm. An important goal of prenatal gene therapy research is to develop clinically relevant techniques that could be applied to cure or ameliorate human disease in utero on large animal models such as sheep or nonhuman primates. Equally important is the use of these models to monitor for potential adverse effects of such interventions. These large animal models provide good representation of individual patient-based investigations. However, analyses that require defined genetic backgrounds, high throughput, defined variability and statistical analyses, e.g. for initial studies on teratogenic and oncogenic effects, are best performed on larger groups of small animals, in particular mice. This chapter gives an overview of the potential adverse effects in relation to prenatal gene therapy and describes the techniques that can be used experimentally in a large animal model to monitor the potential adverse consequences of prenatal gene therapy, with relevance to clinical application. The sheep model is particularly useful to allow serial monitoring of fetal growth and well-being after delivery of prenatal gene therapy. It is also amenable to serially sampling using minimally invasive and clinically relevant techniques such as ultrasound-guided blood sampling. For more invasive long-term monitoring, we

  9. The relevance to humans of animal models for inhalation studies of cancer in the nose and upper airways.

    PubMed

    DeSesso, J M

    1993-09-01

    While nasal cancer is relatively rare among the general population, workers in the nickel refining, leather manufacturing, and furniture building industries exhibit increased incidences of nasal cancer. To investigate the causes of nasal cancer and to design ameliorative strategies, an appropriate animal model for the human upper respiratory regions is required. The present report describes, compares, and assesses the anatomy and physiology of the nasal passages and upper airways of humans, rats, and monkeys for the purpose of determining a relevant animal model in which to investigate potential causes of nasal cancer. Based on the mode of breathing, overall geometry of the nasal passages, relative nasal surface areas, proportions of nasal surfaces lined by various epithelia, mucociliary clearance patterns, and inspiratory airflow routes, the rat, which is very different from humans, is a poor model. In contrast, the monkey exhibits many similarities to humans. Although the monkey does differ from humans in that it exhibits a more rapid respiratory rate, smaller minute and tidal volumes, larger medial turbinate, and a vestibular wing that creates an anterior vortex during inspiration, it offers a more appropriate model for studying the toxic effects of inhaled substances on the nasal passages and extrapolating the findings to humans.

  10. Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study

    PubMed Central

    Margulies, Susan S.; Kilbaugh, Todd; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Byro, Melissa; Saliga, Kristen; Costine, Beth A.; Duhaime, Ann-Christine

    2015-01-01

    We have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post-TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short-term treatment efficacy after 24 h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI. PMID:25904045

  11. Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study.

    PubMed

    Margulies, Susan S; Kilbaugh, Todd; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Byro, Melissa; Saliga, Kristen; Costine, Beth A; Duhaime, Ann-Christine

    2015-05-01

    We have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post-TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short-term treatment efficacy after 24 h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI.

  12. A canine model of septic shock: balancing animal welfare and scientific relevance.

    PubMed

    Minneci, Peter C; Deans, Katherine J; Hansen, Bernie; Parent, Chantal; Romines, Chris; Gonzales, Denise A; Ying, Sai-Xia; Munson, Peter; Suffredini, Anthony F; Feng, Jing; Solomon, Michael A; Banks, Steven M; Kern, Steven J; Danner, Robert L; Eichacker, Peter Q; Natanson, Charles; Solomon, Steven B

    2007-10-01

    A shock canine pneumonia model that permitted relief of discomfort with the use of objective criteria was developed and validated. After intrabronchial Staphylococcus aureus challenge, mechanical ventilation, antibiotics, fluids, vasopressors, sedatives, and analgesics were titrated based on algorithms for 96 h. Increasing S. aureus (1 to 8 x 10(9) colony-forming units/kg) produced decreasing survival rates (P = 0.04). From 4 to 96 h, changes in arterial-alveolar oxygen gradients, mean pulmonary artery pressure, IL-1, serum sodium levels, mechanical ventilation, and vasopressor support were ordered based on survival time [acute nonsurvivors (< or =24 h until death, n = 8) > or = subacute nonsurvivors (>24 to 96 h until death, n = 8) > or = survivors (> or =96 h until death, n = 22) (all P < 0.05)]. In the first 12 h, increases in lactate and renal abnormalities were greatest in acute nonsurvivors (all P < 0.05). Compared with survivors, subacute nonsurvivors had greater rises in cytokines and liver enzymes and greater falls in platelets, white cell counts, pH, and urine output from 24 to 96 h (all P < 0.05). Importantly, these changes were not attributable to dosages of sedation, which decreased in nonsurvivors [survivors vs. nonsurvivors: 5.0 +/- 1.0 vs. 3.8 +/- 0.7 ml x h(-1) x (fentanyl/midazolam/ medetomidine)(-1); P = 0.02]. In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis. The integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsis.

  13. Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

    PubMed Central

    Balmus, Ioana Miruna; Dobrin, Romeo; Timofte, Daniel

    2016-01-01

    The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID:27563374

  14. Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches.

    PubMed

    Balmus, Ioana Miruna; Ciobica, Alin; Antioch, Iulia; Dobrin, Romeo; Timofte, Daniel

    2016-01-01

    The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context.

  15. Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells

    PubMed Central

    Mimeault, Murielle; Batra, Surinder K.

    2012-01-01

    Recent development of animal models relevant to human prostate cancer (PC) etiopathogenesis has provided important information on the specific functions provided by key gene products altered during disease initiation and progression to locally invasive, metastatic and hormone-refractory stages. Especially, the characterization of transgenic mouse models has indicated that the inactivation of distinct tumor suppressor proteins such as phosphatase tensin homolog deleted on chromosome 10 (PTEN), Nkx3.1, p27KIP1 and p53 and retinoblastoma (pRb) may cooperate for the malignant transformation of prostatic stem/progenitor cells into PC stem/progenitor cells and tumor development and metastases. Moreover, the sustained activation of diverse oncogenic signaling elements, including epidermal growth factor receptor (EGFR), sonic hedgehog, Wnt/β-catenin, c-Myc, Akt and nuclear factor-kappaB (NF-κB) also may contribute to the acquisition of more aggressive and hormone-refractory phenotypes by PC stem/progenitor cells and their progenies during disease progression. Importantly, it has also been shown that an enrichment of PC stem/progenitor cells expressing stem cell-like markers may occur after androgen deprivation therapy and docetaxel treatment in the transgenic mouse models of PC suggesting the critical implication of these immature PC cells in treatment resistance, tumor re-growth and disease recurrence. Of clinical interest, the molecular targeting of distinct gene products altered in PC cells by using different dietary compounds has also been shown to counteract PC initiation and progression in animal models supporting their potential use as chemopreventive or chemotherapeutic agents for eradicating the total tumor cell mass, improving current anti-hormonal and chemotherapies and preventing disease relapse. PMID:21396984

  16. Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin.

    PubMed

    Bernal, Antonio; Mahía, Javier; Puerto, Amadeo

    2016-07-01

    The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

  17. Diaphragm Muscle Adaptation to Sustained Hypoxia: Lessons from Animal Models with Relevance to High Altitude and Chronic Respiratory Diseases

    PubMed Central

    Lewis, Philip; O'Halloran, Ken D.

    2016-01-01

    The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function. PMID:28018247

  18. Diaphragm Muscle Adaptation to Sustained Hypoxia: Lessons from Animal Models with Relevance to High Altitude and Chronic Respiratory Diseases.

    PubMed

    Lewis, Philip; O'Halloran, Ken D

    2016-01-01

    The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

  19. Animal Models of Nicotine Exposure: Relevance to Second-Hand Smoking, Electronic Cigarette Use, and Compulsive Smoking

    PubMed Central

    Cohen, Ami; George, Olivier

    2013-01-01

    Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake. PMID:23761766

  20. [Animal models of Charcot-Marie-Tooth disease and their relevance for understanding the disease in humans].

    PubMed

    Bouhy, D; Timmerman, V

    2013-12-01

    Charcot-Marie-Tooth neuropathies (CMT) are inherited neuromuscular disorders caused by length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are responsible for Charcot-Marie-Tooth neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity renders the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodents and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. The majority of these models concern the demyelinating form (type 1) of the disease. The axonal form (type 2) is less common. Both forms can further be divided into multiple subtypes reflecting the heterogeneity of the disease. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how some of them led to clinical trials. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Animal Models to Study Links between Cardiovascular Disease and Renal Failure and Their Relevance to Human Pathology

    PubMed Central

    Hewitson, Tim D.; Holt, Stephen G.; Smith, Edward R.

    2015-01-01

    The close association between cardiovascular pathology and renal dysfunction is well documented and significant. Patients with conventional risk factors for cardiovascular disease like diabetes and hypertension also suffer renal dysfunction. This is unsurprising if the kidney is simply regarded as a “modified blood vessel” and thus, traditional risk factors will affect both systems. Consistent with this, it is relatively easy to comprehend how patients with either sudden or gradual cardiac and or vascular compromise have changes in both renal hemodynamic and regulatory systems. However, patients with pure or primary renal dysfunction also have metabolic changes (e.g., oxidant stress, inflammation, nitric oxide, or endocrine changes) that affect the cardiovascular system. Thus, cardiovascular and renal systems are intimately, bidirectionally and inextricably linked. Whilst we understand several of these links, some of the mechanisms for these connections remain incompletely explained. Animal models of cardiovascular and renal disease allow us to explore such mechanisms, and more importantly, potential therapeutic strategies. In this article, we review various experimental models used, and examine critically how representative they are of the human condition. PMID:26441970

  2. Extinction of drug- and withdrawal-paired cues in animal models: Relevance to the treatment of addiction

    PubMed Central

    Myers, Karyn M.; Carlezon, William A.

    2010-01-01

    Conditioned drug craving and withdrawal elicited by cues paired with drug use or acute withdrawal are among the many factors contributing to compulsive drug taking. Understanding how to stop these cues from having these effects is a major goal of addiction research. Extinction is a form of learning in which associations between cues and the events they predict are weakened by exposure to the cues in the absence of those events. Evidence from animal models suggests that conditioned responses to drug cues can be extinguished, although the degree to which this occurs in humans is controversial. Investigations into the neurobiological substrates of extinction of conditioned drug craving and withdrawal may facilitate the successful use of drug cue extinction within clinical contexts. While this work is still in the early stages, there are indications that extinction of drug- and withdrawal-paired cues shares neural mechanisms with extinction of conditioned fear. Using the fear extinction literature as a template, it is possible to organize the observations on drug cue extinction into a cohesive framework. PMID:20109490

  3. Extinction of drug- and withdrawal-paired cues in animal models: relevance to the treatment of addiction.

    PubMed

    Myers, Karyn M; Carlezon, William A

    2010-11-01

    Conditioned drug craving and withdrawal elicited by cues paired with drug use or acute withdrawal are among the many factors contributing to compulsive drug taking. Understanding how to stop these cues from having these effects is a major goal of addiction research. Extinction is a form of learning in which associations between cues and the events they predict are weakened by exposure to the cues in the absence of those events. Evidence from animal models suggests that conditioned responses to drug cues can be extinguished, although the degree to which this occurs in humans is controversial. Investigations into the neurobiological substrates of extinction of conditioned drug craving and withdrawal may facilitate the successful use of drug cue extinction within clinical contexts. While this work is still in the early stages, there are indications that extinction of drug- and withdrawal-paired cues shares neural mechanisms with extinction of conditioned fear. Using the fear extinction literature as a template, it is possible to organize the observations on drug cue extinction into a cohesive framework. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. The clinical relevance of animal models in Sjögren's syndrome: the interferon signature from mouse to man.

    PubMed

    Maria, Naomi I; Vogelsang, Petra; Versnel, Marjan A

    2015-07-03

    Mouse models have been widely used to elucidate the pathogenic mechanisms of human diseases. The advantages of using these models include the ability to study different stages of the disease with particular respect to specific target organs, to focus on the role of specific pathogenic factors and to investigate the effect of possible therapeutic interventions. Sjögren's syndrome (SS) is a systemic autoimmune disease, characterised by lymphocytic infiltrates in the salivary and lacrimal glands. To date, effective therapy is not available and treatment has been mainly symptomatic. Ongoing studies in murine models are aimed at developing more effective and targeted therapies in SS. The heterogeneity of SS will most probably benefit from optimising therapies, tailored to specific subgroups of the disease. In this review, we provide our perspective on the importance of subdividing SS patients according to their interferon signature, and recommend choosing appropriate mouse models for interferon-positive and interferon-negative SS subtypes. Murine models better resembling human-disease phenotypes will be essential in this endeavour.

  5. Animal models of schizophrenia

    PubMed Central

    Jones, CA; Watson, DJG; Fone, KCF

    2011-01-01

    Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble ‘positive-like’ symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed. LINKED ARTICLES This article is part of a themed issue on

  6. Challenges and issues with streptozotocin-induced diabetes - A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics.

    PubMed

    Goyal, Sameer N; Reddy, Navya M; Patil, Kalpesh R; Nakhate, Kartik T; Ojha, Shreesh; Patil, Chandragouda R; Agrawal, Yogeeta O

    2016-01-25

    Streptozotocin (STZ) has been extensively used over the last three decades to induce diabetes in various animal species and to help screen for hypoglycemic drugs. STZ induces clinical features in animals that resemble those associated with diabetes in humans. For this reason STZ treated animals have been used to study diabetogenic mechanisms and for preclinical evaluation of novel antidiabetic therapies. However, the physiochemical characteristics and associated toxicities of STZ are still major obstacles for researchers using STZ treated animals to investigate diabetes. Another major challenges in STZ-induced diabetes are sustaining uniformity, suitability, reproducibility and induction of diabetes with minimal animal lethality. Lack of appropriate use of STZ was found to be associated with increased mortality and animal suffering. During STZ use in animals, attention should be paid to several factors such as method of preparation of STZ, stability, suitable dose, route of administration, diet regimen, animal species with respect to age, body weight, gender and the target blood glucose level used to represent hyperglycemia. Therefore, protocol for STZ-induced diabetes in experimental animals must be meticulously planned. This review highlights specific skills and strategies involved in the execution of STZ-induced diabetes model. The present review aims to provide insight into diabetogenic mechanisms of STZ, specific toxicity of STZ with its significance and factors responsible for variations in diabetogenic effects of STZ. Further this review also addresses ways to minimize STZ-induced mortality, suggests methods to improve STZ-based experimental models and best utilize them for experimental studies purported to understand diabetes pathogenesis and preclinical evaluation of drugs.

  7. Animal model of dermatophytosis.

    PubMed

    Shimamura, Tsuyoshi; Kubota, Nobuo; Shibuya, Kazutoshi

    2012-01-01

    Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects.

  8. Animal Model of Dermatophytosis

    PubMed Central

    Shimamura, Tsuyoshi; Kubota, Nobuo; Shibuya, Kazutoshi

    2012-01-01

    Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects. PMID:22619489

  9. Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals

    PubMed Central

    Amiot, Catherine E.; Bastian, Brock

    2017-01-01

    Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals. PMID:28045909

  10. Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals.

    PubMed

    Amiot, Catherine E; Bastian, Brock

    2017-01-01

    Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals.

  11. Modelling Farm Animal Welfare

    PubMed Central

    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. Inositol-deficient food augments a behavioral effect of long-term lithium treatment mediated by inositol monophosphatase inhibition: an animal model with relevance for bipolar disorder.

    PubMed

    Shtein, Liza; Agam, Galila; Belmaker, R H; Bersudsky, Yuly

    2015-04-01

    Lithium treatment in rodents markedly enhances cholinergic agonists such as pilocarpine. This effect can be reversed in a stereospecific manner by administration of inositol, suggesting that the effect of lithium is caused by inositol monophosphatase inhibition and consequent inositol depletion. If so, inositol-deficient food would be expected to enhance lithium effects. Inositol-deficient food was prepared from inositol-free ingredients. Mice with a homozygote knockout of the inositol monophosphatase 1 gene unable to synthesize inositol endogenously and mimicking lithium-treated animals were fed this diet or a control diet. Lithium-treated wild-type animals were also treated with the inositol-deficient diet or control diet. Pilocarpine was administered after 1 week of treatment, and behavior including seizures was assessed using rating scale. Inositol-deficient food-treated animals, both lithium treated and with inositol monophosphatase 1 knockout, had significantly elevated cholinergic behavior rating and significantly increased or earlier seizures compared with the controls. The effect of inositol-deficient food supports the role of inositol depletion in the effects of lithium on pilocarpine-induced behavior. However, the relevance of this behavior to other more mood-related effects of lithium is not clear.

  13. Animal models in burn research.

    PubMed

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

    2014-09-01

    Burn injury is a severe form of trauma affecting more than 2 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 to 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 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.

  14. Animal Models in Burn Research

    PubMed Central

    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

  15. Animal models of scoliosis.

    PubMed

    Bobyn, Justin D; Little, David G; Gray, Randolph; Schindeler, Aaron

    2015-04-01

    Multiple techniques designed to induce scoliotic deformity have been applied across many animal species. We have undertaken a review of the literature regarding experimental models of scoliosis in animals to discuss their utility in comprehending disease aetiology and treatment. Models of scoliosis in animals can be broadly divided into quadrupedal and bipedal experiments. Quadrupedal models, in the absence of axial gravitation force, depend upon development of a mechanical asymmetry along the spine to initiate a scoliotic deformity. Bipedal models more accurately mimic human posture and consequently are subject to similar forces due to gravity, which have been long appreciated to be a contributing factor to the development of scoliosis. Many effective models of scoliosis in smaller animals have not been successfully translated to primates and humans. Though these models may not clarify the aetiology of human scoliosis, by providing a reliable and reproducible deformity in the spine they are a useful means with which to test interventions designed to correct and prevent deformity.

  16. Animal Models of Bone Metastasis

    PubMed Central

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  17. Animal models of hepatotoxicity.

    PubMed

    Bhakuni, Ganesh Singh; Bedi, Onkar; Bariwal, Jitender; Deshmukh, Rahul; Kumar, Puneet

    2016-01-01

    Liver is the largest and important organ in the body, involved in the metabolism of food and drugs. Liver diseases are potentially life threatening for humans. The etiology of liver disorder varied due to different reasons like autoimmune disorder, viral infection, toxic chemical, and due to changing diet style. Liver injury produces pathological changes like increase level of SGOT, SGPT, TB and generation of free radical radicals. A better understanding of primary mechanisms is mandatory for designing of new therapeutic drugs. Therefore, animal models are being developed to mimic human liver diseases. Animal models are being used for several decades to study the pathogenesis of liver disorders and related toxicities. In this review, we revealed various animal models with their merits and demerits. Our main focus is to explore all new and traditional animal models under broad classification like non-invasive, invasive and genetic models which directly or indirectly produce hepatotoxicity.

  18. Animal models for osteoporosis

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.

    2001-01-01

    Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

  19. Animal models for osteoporosis

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.

    2001-01-01

    Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

  20. Animal models of tinnitus.

    PubMed

    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

  1. Animal models of sarcoidosis.

    PubMed

    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.

  2. Animal models for osteoporosis.

    PubMed

    Komori, Toshihisa

    2015-07-15

    The major types of osteoporosis in humans are postmenopausal osteoporosis, disuse osteoporosis, and glucocorticoid-induced osteoporosis. Animal models for postmenopausal osteoporosis are generated by ovariectomy. Bone loss occurs in estrogen deficiency due to enhanced bone resorption and impaired osteoblast function. Estrogen receptor α induces osteoclast apoptosis, but the mechanism for impaired osteoblast function remains to be clarified. Animal models for unloading are generated by tail suspension or hind limb immobilization by sciatic neurectomy, tenotomy, or using plaster cast. Unloading inhibits bone formation and enhances bone resorption, and the involvement of the sympathetic nervous system in it needs to be further investigated. The osteocyte network regulates bone mass by responding to mechanical stress. Osteoblast-specific BCL2 transgenic mice, in which the osteocyte network is completely disrupted, can be a mouse model for the evaluation of osteocyte functions. Glucocorticoid treatment inhibits bone formation and enhances bone resorption, and markedly reduces cancellous bone in humans and large animals, but not consistently in rodents.

  3. Cyclic Hematopoiesis: animal models

    SciTech Connect

    Jones, J.B.; Lange, R.D.

    1983-08-01

    The four existing animal models of cyclic hematopoiesis are briefly described. The unusual erythropoietin (Ep) responses of the W/Wv mouse, the Sl/Sld mouse, and cyclic hematopoietic dog are reviewed. The facts reviewed indicate that the bone marrow itself is capable of influencing regulatory events of hematopoiesis.

  4. [Law, guidelines and standards relevant to laboratory animals and animal experimentation].

    PubMed

    Takagaki, Y

    1982-04-01

    Presently available laws guidelines and standards relevant to laboratory animals and animal experimentation are reviewed. In Japan there exist Animal Protection and Management Act, and the Guideline for Animal Care and Management which was later prepared in accordance with the former act. These are comparable in quality to those seen in foreign countries such as the Cruelty to Animals Act of Great Britain or the Animal Welfare Act of U.S.A. As for laboratory animals, however, only basic matters appear there, and that is why the Japanese National Academy of Science in 1980 proposed legislation of a guideline for animal experimentation to the government. It is awaited to legislate sooner the one comparable to the Guidelines for the Regulation of Animal Experimentation prepared by ICLA in 1974. Other laws and regulations referred and discussed here are: *standards and guidelines for breeding, care and management of laboratory animals *veterinary laws and regulations which should be referred when domestic or wild animals are to be used for experiments *laws and regulations for general housing construction and environmental protection *regulations for particular experiments where radioisotopes, microbial infections or recombinant DNA are in use

  5. Animal Models of Atherosclerosis

    PubMed Central

    Getz, Godfrey S.; Reardon, Catherine A.

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

  6. Animal Models of Hemophilia

    PubMed Central

    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

  7. Animal Models of Sleep Disorders

    PubMed Central

    Toth, Linda A; Bhargava, Pavan

    2013-01-01

    Problems with sleep affect a large part of the general population, with more than half of all people in the United States reporting difficulties with sleep or insufficient sleep at various times and about 40 million affected chronically. Sleep is a complex physiologic process that is influenced by many internal and environmental factors, and problems with sleep are often related to specific personal circumstances or are based on subjective reports from the affected person. Although human subjects are used widely in the study of sleep and sleep disorders, the study of animals has been invaluable in developing our understanding about the physiology of sleep and the underlying mechanisms of sleep disorders. Historically, the use of animals for the study of sleep disorders has arguably been most fruitful for the condition of narcolepsy, in which studies of dogs and mice revealed previously unsuspected mechanisms for this condition. The current overview considers animal models that have been used to study 4 of the most common human sleep disorders—insomnia, narcolepsy, restless legs syndrome, and sleep apnea—and summarizes considerations relevant to the use of animals for the study of sleep and sleep disorders. Animal-based research has been vital to the elucidation of mechanisms that underlie sleep, its regulation, and its disorders and undoubtedly will remain crucial for discovering and validating sleep mechanisms and testing interventions for sleep disorders. PMID:23582416

  8. Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes.

    PubMed

    Bouderba, Saida; Sanchez-Martin, Carlos; Villanueva, Gloria R; Detaille, Dominique; Koceïr, E Ahmed

    2014-03-01

    Insulin resistance and oxidative stress are major pathogenic mechanisms leading to chronic liver diseases in diabetic subjects. The gerbil Psammomys obesus is a unique model of nutritional diabetes resembling the disease in humans. This study investigated whether the natural ingredient silibinin, known as hepatoprotective, could decrease oxidative stress and reduce liver damage in obese gerbils. Control animals were fed their vegetable-based low caloric diet while two other rat groups ingested a high calorie diet for 14 weeks. Silibinin, or its vehicle, was administrated by gastric intubation (100 mg/kg per day) from the 7th week of treatment, which corresponds to an established insulin resistance state. At the end of the experiments, the hepatic biochemical profile, markers of oxidative stress in either plasma or liver tissue, and histological alterations were examined. Diabetic P. obesus displayed many metabolic disturbances (hyperinsulinemia, hyperglycemia, dyslipidemia), which were aggravated for the last 8 weeks. These events were coupled with greater oxidative stress (decline in glutathione, rise in lipoperoxidation). In addition, glutathione peroxidase activity was reduced while the level of superoxide dismutase was elevated. Interestingly, treatment with silibinin alleviated most of the metabolic defects, especially high triglyceride levels, reduced insulin resistance and largely restored antioxidant status. Also, Masson's trichrome staining revealed distinct steatosis, yet silibinin partially reversed this manifestation. Silibinin affords substantial protection against the progression of insulin resistance in Type 2 diabetes mellitus for P. obesus by hampering the oxidative process and improving hepatic metabolism. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  9. The development of animal personality: relevance, concepts and perspectives.

    PubMed

    Stamps, Judy; Groothuis, Ton G G

    2010-05-01

    Recent studies of animal personality have focused on its proximate causation and its ecological and evolutionary significance, but have mostly ignored questions about its development, although an understanding of the latter is highly relevant to these other questions. One possible reason for this neglect is confusion about many of the concepts and terms that are necessary to study the development of animal personality. Here, we provide a framework for studying personality development that focuses on the properties of animal personality, and considers how and why these properties may change over time. We specifically focus on three dimensions of personality: (1) contextual generality at a given age or time, (2) temporal consistency in behavioural traits and in relationships between traits, and (3) the effects of genes and experience on the development of personality at a given age or life stage. We advocate using a new approach, contextual reaction norms, to study the contextual generality of personality traits at the level of groups, individuals and genotypes, show how concepts and terms borrowed from the literature on personality development in humans can be used to study temporal changes in personality at the level of groups and individuals, and demonstrate how classical developmental reaction norms can provide insights into the ways that genes and experiential factors interact across ontogeny to affect the expression of personality traits. In addition, we discuss how correlations between the effects of genes and experience on personality development can arise as a function of individuals' control over their own environment, via niche-picking or niche-construction. Using this framework, we discuss several widely held assumptions about animal personality development that still await validation, identify neglected methodological issues, and describe a number of promising new avenues for future research.

  10. Animal models of narcolepsy.

    PubMed

    Chen, Lichao; Brown, Ritchie E; McKenna, James T; McCarley, Robert W

    2009-08-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered mouse and rat models of narcolepsy. To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models.

  11. Animal models of atherosclerosis.

    PubMed

    Emini Veseli, Besa; Perrotta, Paola; De Meyer, Gregory R A; Roth, Lynn; Van der Donckt, Carole; Martinet, Wim; De Meyer, Guido R Y

    2017-05-05

    An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis. Mouse and rabbit models have been mostly used, followed by pigs and non-human primates. Each of these models has its advantages and limitations. The mouse has become the predominant species to study experimental atherosclerosis because of its rapid reproduction, ease of genetic manipulation and its ability to monitor atherogenesis in a reasonable time frame. Both Apolipoprotein E deficient (ApoE(-/-)) and LDL-receptor (LDLr) knockout mice have been frequently used, but also ApoE/LDLr double-knockout, ApoE3-Leiden and PCSK9-AAV mice are valuable tools in atherosclerosis research. However, a great challenge was the development of a model in which intra-plaque microvessels, haemorrhages, spontaneous atherosclerotic plaque ruptures, myocardial infarction and sudden death occur consistently. These features are present in ApoE(-/-)Fbn1(C1039G+/-) mice, which can be used as a validated model in pre-clinical studies to evaluate novel plaque-stabilizing drugs. Copyright © 2017. Published by Elsevier B.V.

  12. Animal models of adrenocortical tumorigenesis

    PubMed Central

    Beuschlein, Felix; Galac, Sara; Wilson, David B.

    2011-01-01

    Over the past decade, research on human adrenocortical neoplasia has been dominated by gene expression profiling of tumor specimens and by analysis of genetic disorders associated with a predisposition to these tumors. Although these studies have identified key genes and associated signaling pathways that are dysregulated in adrenocortical neoplasms, the molecular events accounting for the frequent occurrence of benign tumors and low rate of malignant transformation remain unknown. Moreover, the prognosis for patients with adrenocortical carcinoma remains poor, so new medical treatments are needed. Naturally occurring and genetically engineered animal models afford a means to investigate adrenocortical tumorigenesis and to develop novel therapeutics. This comparative review highlights adrenocortical tumor models useful for either mechanistic studies or preclinical testing. Three model species – mouse, ferret, and dog – are reviewed, and their relevance to adrenocortical tumors in humans is discussed. PMID:22100615

  13. Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans.

    PubMed

    Hatton, Grace B; Yadav, Vipul; Basit, Abdul W; Merchant, Hamid A

    2015-09-01

    "All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

  14. Relevance of experimental animal studies to the human experience

    SciTech Connect

    Fry, R.J.M.

    1982-01-01

    Animal experiments are being used to examine a number of physical and biological factors that influence risk estimations though not usually in coordination with epidemiologists. It is clear that the different mechanisms involved in different types of tumors are reflected in the diversity of dose-response relationships. The forms of the dose-response relationships are influenced by both the initial events and their expression. Evidence is accumulating that many initiated cells do not get expressed as overt cancers and host factors may play a major role in the expression of potential tumor cells. There is a need for information about the relationship of the natural incidence and susceptibility to radiation induction for more tumor types. Such experiments will help answer the question of which risk estimate models are appropriate for different tumor types and can be carried out on animals. Perhaps because of the importance of host factors risk estimates as a percentage of the natural incidence appear to be similar for human beings and mice for a small number of tumor types. The elucidation of the mechanisms involved in different tissues while a slow business remains an important role of animal experiments.

  15. Goal relevance as a quantitative model of human task relevance.

    PubMed

    Tanner, James; Itti, Laurent

    2017-03-01

    The concept of relevance is used ubiquitously in everyday life. However, a general quantitative definition of relevance has been lacking, especially as pertains to quantifying the relevance of sensory observations to one's goals. We propose a theoretical definition for the information value of data observations with respect to a goal, which we call "goal relevance." We consider the probability distribution of an agent's subjective beliefs over how a goal can be achieved. When new data are observed, its goal relevance is measured as the Kullback-Leibler divergence between belief distributions before and after the observation. Theoretical predictions about the relevance of different obstacles in simulated environments agreed with the majority response of 38 human participants in 83.5% of trials, beating multiple machine-learning models. Our new definition of goal relevance is general, quantitative, explicit, and allows one to put a number onto the previously elusive notion of relevance of observations to a goal. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Animal models of RLS phenotypes.

    PubMed

    Allen, Richard P; Donelson, Nathan C; Jones, Byron C; Li, Yuqing; Manconi, Mauro; Rye, David B; Sanyal, Subhabrata; Winkelmann, Juliane

    2017-03-01

    Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements.

  17. Optimization of high grade glioma cell culture from surgical specimens for use in clinically relevant animal models and 3D immunochemistry.

    PubMed

    Hasselbach, Laura A; Irtenkauf, Susan M; Lemke, Nancy W; Nelson, Kevin K; Berezovsky, Artem D; Carlton, Enoch T; Transou, Andrea D; Mikkelsen, Tom; deCarvalho, Ana C

    2014-01-07

    Glioblastomas, the most common and aggressive form of astrocytoma, are refractory to therapy, and molecularly heterogeneous. The ability to establish cell cultures that preserve the genomic profile of the parental tumors, for use in patient specific in vitro and in vivo models, has the potential to revolutionize the preclinical development of new treatments for glioblastoma tailored to the molecular characteristics of each tumor. Starting with fresh high grade astrocytoma tumors dissociated into single cells, we use the neurosphere assay as an enrichment method for cells presenting cancer stem cell phenotype, including expression of neural stem cell markers, long term self-renewal in vitro, and the ability to form orthotopic xenograft tumors. This method has been previously proposed, and is now in use by several investigators. Based on our experience of dissociating and culturing 125 glioblastoma specimens, we arrived at the detailed protocol we present here, suitable for routine neurosphere culturing of high grade astrocytomas and large scale expansion of tumorigenic cells for preclinical studies. We report on the efficiency of successful long term cultures using this protocol and suggest affordable alternatives for culturing dissociated glioblastoma cells that fail to grow as neurospheres. We also describe in detail a protocol for preserving the neurospheres 3D architecture for immunohistochemistry. Cell cultures enriched in CSCs, capable of generating orthotopic xenograft models that preserve the molecular signatures and heterogeneity of GBMs, are becoming increasingly popular for the study of the biology of GBMs and for the improved design of preclinical testing of potential therapies.

  18. Optimization of High Grade Glioma Cell Culture from Surgical Specimens for Use in Clinically Relevant Animal Models and 3D Immunochemistry

    PubMed Central

    Hasselbach, Laura A.; Irtenkauf, Susan M.; Lemke, Nancy W.; Nelson, Kevin K.; Berezovsky, Artem D.; Carlton, Enoch T.; Transou, Andrea D.; Mikkelsen, Tom; deCarvalho, Ana C.

    2014-01-01

    Glioblastomas, the most common and aggressive form of astrocytoma, are refractory to therapy, and molecularly heterogeneous. The ability to establish cell cultures that preserve the genomic profile of the parental tumors, for use in patient specific in vitro and in vivo models, has the potential to revolutionize the preclinical development of new treatments for glioblastoma tailored to the molecular characteristics of each tumor. Starting with fresh high grade astrocytoma tumors dissociated into single cells, we use the neurosphere assay as an enrichment method for cells presenting cancer stem cell phenotype, including expression of neural stem cell markers, long term self-renewal in vitro, and the ability to form orthotopic xenograft tumors. This method has been previously proposed, and is now in use by several investigators. Based on our experience of dissociating and culturing 125 glioblastoma specimens, we arrived at the detailed protocol we present here, suitable for routine neurosphere culturing of high grade astrocytomas and large scale expansion of tumorigenic cells for preclinical studies. We report on the efficiency of successful long term cultures using this protocol and suggest affordable alternatives for culturing dissociated glioblastoma cells that fail to grow as neurospheres. We also describe in detail a protocol for preserving the neurospheres 3D architecture for immunohistochemistry. Cell cultures enriched in CSCs, capable of generating orthotopic xenograft models that preserve the molecular signatures and heterogeneity of GBMs, are becoming increasingly popular for the study of the biology of GBMs and for the improved design of preclinical testing of potential therapies. PMID:24429465

  19. Animal models in gerontology research.

    PubMed

    Nadon, Nancy L

    2007-01-01

    Animal models have paved the way for the vast majority of advances in biomedical research. Studies on aged animals are essential for understanding the processes inherent in normal aging and the progression of age-related diseases. Animal models are used to identify physiological changes with age, to identify the genetic basis of normal aging and age-associated disease and degeneration, and to test potential therapeutic interventions. This chapter will focus on rodent models and will summarize important considerations for the use of animals in aging research in general and in modeling geriatric epilepsy.

  20. ANIMAL MODELS FOR IMMUNOTOXICITY

    EPA Science Inventory

    Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...

  1. ANIMAL MODELS FOR IMMUNOTOXICITY

    EPA Science Inventory

    Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...

  2. Animal Models of Colorectal Cancer

    PubMed Central

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  3. [Psoriasis in the animal model].

    PubMed

    Boehncke, W H

    1997-10-01

    Co-existing inflammation and epidermal hyperproliferation characteristic for psoriasis have been shown to be reproducible in several animal models utilizing a variety of different strategies. These models highlight some points of the multicausal pathogenesis of psoriasis. Based on observations made in the animal models, a hypothesis is proposed for the pathogenesis of psoriasis, the elements of which can be tested in a recently established xenogeneic transplantation model.

  4. [Animal models for vascular calcification].

    PubMed

    Ikeda, Koji; Nakagawa, Yusuke; Matsubara, Hiroaki

    2010-11-01

    Analysis of animal models is indispensable to elucidate the molecular mechanism in vascular calcification (VC) as well as to develop new therapies for VC. Various gene-modified mice that show VC have been reported, and considerable progress has been made through the analyses of these animals. Mice of which bone-calcification regulatory factors were modified are the representative animal models for VC, indicating that these factors certainly regulate VC as well as bone-calcification. Inducible VC in wild-type animals is also an important research tool for developing preventive and therapeutic approach for VC.

  5. Animal Models of Diabetic Retinopathy.

    PubMed

    Jiang, Xiaoyan; Yang, Lizhu; Luo, Yan

    2015-01-01

    Diabetic retinopathy (DR) is one of today's main causes of blindness in numerous developed countries worldwide. The underlying pathogenesis of DR is complex and not well understood, thus impeding development of specific, effective treatment modalities. Consequently, the use of animal models of DR is of critical importance for investigating the pathogenesis of and treatment for DR. While rats and mice are the most commonly used animal models of DR, the zebrafish now appears to be a promising model. Nonhuman primates and humans have similar eye structures, and both can develop spontaneous diabetes mellitus (DM). Although various traditionally used animal models of DR undergo a number of pathological changes similar to those of human DR, several human variations, e.g. retinal neovascularization, cannot yet be fully mimicked in any existing animal model of DM. Since both the animal models and the methods chosen for inducing DR have great influence on experimental results, a clear understanding of available animal models is vital for planning an experimental design. In this review, we summarize the mechanisms, methodologies and pros and cons of the most commonly used animal models of DR.

  6. Animal models of scleroderma: recent progress.

    PubMed

    Marangoni, Roberta G; Varga, John; Tourtellotte, Warren G

    2016-11-01

    We discuss recent advances in evaluating and optimizing animal models of systemic sclerosis (SSc). Such models could be of value for illuminating etiopathogenesis using hypothesis-testing experimental approaches, for developing effective disease-modifying therapies, and for uncovering clinically relevant biomarkers. We describe recent advances in previously reported and novel animal models of SSc. The limitations of each animal model and their ability to recapitulate the pathophysiology of recognized molecular subsets of SSc are discussed. We highlight attrition of dermal white adipose tissue as a consistent pathological feature of dermal fibrosis in mouse models, and its relevance to SSc-associated cutaneous fibrosis. Several animal models potentially useful for studying SSc pathogenesis have been described. Recent studies highlight particular strengths and weaknesses of selected models in recapitulating distinct features of the human disease. When used in the appropriate experimental setting, and in combination, these models singly and together provide a powerful set of in-vivo tools to define underlying mechanisms of disease and to develop and evaluate effective antifibrotic therapies.

  7. Research ethics in animal models.

    PubMed

    Miziara, Ivan Dieb; Magalhães, Ana Tereza de Matos; Santos, Maruska d'Aparecida; Gomes, Erika Ferreira; Oliveira, Reinaldo Ayer de

    2012-04-01

    The use of animals in scientific experiments has been described since the fifth century BC. A number of scientific advances in health are attributed to animal models. The issue of the moral status of animals has always been debated. This article aims to review and to present a historical summary of the current laws, to guide researchers who wish to use animal models in otolaryngology research. Research on the medline database. For many years there were no laws ruling the use of animals in scientific experimentation in Brazil. Standards set by national and international organizations were followed. Recently, Law No. 11.794/08 established procedures for the scientific use of animals. Studies in otolaryngology have used the larynxes of rabbits, pigs, dogs, guinea pigs (Cavia porcellus), and mice. There were also studies comparing rabbits, rats, and dogs, rhinoplasty on rabbits, and inner ear studies on rats and guinea pigs (albino). The researchers involved in scientific work with animals should know the principles of Law 11.794/08 and investigate what animals are appropriate for each area of study in their models. Otolaryngologists, especially those dedicated to research, need to be mindful of the ethical rules regarding the use of animals in their studies.

  8. Animal models of erectile dysfunction.

    PubMed

    Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H

    2015-01-01

    Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.

  9. Animal models of cerebral ischemia

    NASA Astrophysics Data System (ADS)

    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.

  10. The Semantic Distance Model of Relevance Assessment.

    ERIC Educational Resources Information Center

    Brooks, Terrence A.

    1998-01-01

    Presents the Semantic Distance Model (SDM) of Relevance Assessment, a cognitive model of the relationship between semantic distance and relevance assessment. Discusses premises of the model such as the subjective nature of information and the metaphor of semantic distance. Empirical results illustrate the effects of semantic distance and semantic…

  11. The Semantic Distance Model of Relevance Assessment.

    ERIC Educational Resources Information Center

    Brooks, Terrence A.

    1998-01-01

    Presents the Semantic Distance Model (SDM) of Relevance Assessment, a cognitive model of the relationship between semantic distance and relevance assessment. Discusses premises of the model such as the subjective nature of information and the metaphor of semantic distance. Empirical results illustrate the effects of semantic distance and semantic…

  12. Animal Models for Candidiasis

    PubMed Central

    Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L.

    2014-01-01

    Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described. PMID:24700323

  13. Animal Models of Bacterial Keratitis

    PubMed Central

    Marquart, Mary E.

    2011-01-01

    Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270

  14. Animal models in myopia research.

    PubMed

    Schaeffel, Frank; Feldkaemper, Marita

    2015-11-01

    Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. © 2015 Optometry

  15. Composite Mandibulectomy: A Novel Animal Model

    PubMed Central

    Sidell, Douglas R.; Aghaloo, Tara; Tetradis, Sotirios; Lee, Min; Bezouglaia, Olga; DeConde, Adam; St. John, Maie A.

    2012-01-01

    Objectives Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well-established small-animal model of the segmental mandibulectomy, including composite resection, does not exist. The objective of this study is the creation of a reliable animal model that can be used to study the reconstruction of en bloc mandibular defects. Surgical techniques and an array of reconstructive options are described. Study design Description of an animal model. Setting Animal laboratory at a quaternary care university medical center. Methods We present an Animal Research Oversight Committee–approved prospective analysis of survival operations in the rat model. A detailed, stepwise description of surgical technique and relevant intraoperative anatomy is presented. Postoperative management, early pitfalls, surgical complications, and future applications are discussed. Results A total of 72 operations were performed by a single individual between July and October 2010. Two intraoperative and 9 postoperative complications were recognized. There were 6 orocutaneous fistulas, 2 abscesses, and 1 seroma. There were 4 fatalities, which were attributed to anesthetic complications (2, intraoperative), hematoma formation (1, postoperative), and foreign-body aspiration (1, postoperative). Conclusion This novel animal model reliably replicates the en bloc segmental mandibular defects seen in our patient population and can be manipulated to achieve a wide variety of research objectives. PMID:22282867

  16. Factors relevant to adoption of cats in an animal shelter.

    PubMed

    Fantuzzi, Jacqueline M; Miller, Katherine A; Weiss, Emily

    2010-01-01

    This study performed a multifactor analysis of the effects of the provision of toys, cage location, and cat characteristics (activity level, age, sex, and coat color) on 111 cats available for adoption in a nonhuman animal shelter. The analysis revealed a greater adopter viewing of cats housed at eye level and of those with toys-even though the toys did not affect the cats' behavior. Adopters viewed cats who were active for longer periods of time. The active cats were more likely to be adopted during the 16-week study than cats who were less active.

  17. Animal models of chronic migraine.

    PubMed

    Storer, Robin James; Supronsinchai, Weera; Srikiatkhachorn, Anan

    2015-01-01

    Many animal models of migraine have been described. Some of them have been useful in the development of new therapies. All of them have their shortcomings. Animal models of chronic migraine have been relatively less frequently described. Whether a rigid distinction between episodic and chronic migraine is useful when their underlying pathophysiology is likely to be the same and that migraine frequency probably depends on complex polygenic influences remains to be determined. Any model of chronic migraine must reflect the chronicity of the disorder and be reliable and validated with pharmacological interventions. Future animal models of chronic migraine are likely to involve recurrent activation of the trigeminal nociceptive system. Valid models would provide a means for investigating pathophysiological mechanism of the transformation from episodic to chronic migraine and may also be used to test the efficacy of potential preventive medications.

  18. Animal and cellular models of Friedreich ataxia.

    PubMed

    Perdomini, Morgane; Hick, Aurore; Puccio, Hélène; Pook, Mark A

    2013-08-01

    The development and use of animal and cellular models of Friedreich ataxia (FRDA) are essential requirements for the understanding of FRDA disease mechanisms and the investigation of potential FRDA therapeutic strategies. Although animal and cellular models of lower organisms have provided valuable information on certain aspects of FRDA disease and therapy, it is intuitive that the most useful models are those of mammals and mammalian cells, which are the closest in physiological terms to FRDA patients. To date, there have been considerable efforts put into the development of several different FRDA mouse models and relevant FRDA mouse and human cell line systems. We summarize the principal mammalian FRDA models, discuss the pros and cons of each system, and describe the ways in which such models have been used to address two of the fundamental, as yet unanswered, questions regarding FRDA. Namely, what is the exact pathophysiology of FRDA and what is the detailed genetic and epigenetic basis of FRDA?

  19. Uncertainty in spatially explicit animal dispersal models

    USGS Publications Warehouse

    Mooij, Wolf M.; DeAngelis, Donald L.

    2003-01-01

    Uncertainty in estimates of survival of dispersing animals is a vexing difficulty in conservation biology. The current notion is that this uncertainty decreases the usefulness of spatially explicit population models in particular. We examined this problem by comparing dispersal models of three levels of complexity: (1) an event-based binomial model that considers only the occurrence of mortality or arrival, (2) a temporally explicit exponential model that employs mortality and arrival rates, and (3) a spatially explicit grid-walk model that simulates the movement of animals through an artificial landscape. Each model was fitted to the same set of field data. A first objective of the paper is to illustrate how the maximum-likelihood method can be used in all three cases to estimate the means and confidence limits for the relevant model parameters, given a particular set of data on dispersal survival. Using this framework we show that the structure of the uncertainty for all three models is strikingly similar. In fact, the results of our unified approach imply that spatially explicit dispersal models, which take advantage of information on landscape details, suffer less from uncertainly than do simpler models. Moreover, we show that the proposed strategy of model development safeguards one from error propagation in these more complex models. Finally, our approach shows that all models related to animal dispersal, ranging from simple to complex, can be related in a hierarchical fashion, so that the various approaches to modeling such dispersal can be viewed from a unified perspective.

  20. Behavioral animal models of depression.

    PubMed

    Yan, Hua-Cheng; Cao, Xiong; Das, Manas; Zhu, Xin-Hong; Gao, Tian-Ming

    2010-08-01

    Depression is a chronic, recurring and potentially life-threatening illness that affects up to 20% of the population across the world. Despite its prevalence and considerable impact on human, little is known about its pathogenesis. One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression. Besides, some core symptoms such as depressed mood, feeling of worthlessness, and recurring thoughts of death or suicide, are impossible to be modeled on laboratory animals. Currently, the criteria for identifying animal models of depression rely on either of the 2 principles: actions of known antidepressants and responses to stress. This review mainly focuses on the most widely used animal models of depression, including learned helplessness, chronic mild stress, and social defeat paradigms. Also, the behavioral tests for screening antidepressants, such as forced swimming test and tail suspension test, are also discussed. The advantages and major drawbacks of each model are evaluated. In prospective, new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.

  1. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    NASA Astrophysics Data System (ADS)

    Halloran, Siobhan; Wexler, Anthony; Ristenpart, William

    2014-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in modulating the pathogen transmission, to date the infectious disease community has paid little attention to the effect of airspeed or turbulence intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of a standard axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We demonstrate that the fan speed counterintuitively has no effect on the downstream plume width, a result replicated with a variety of different fan types and configurations. The results point toward a useful simplification in modeling of airborne disease transmission via fan-generated flows.

  2. Optogenetics in psychiatric animal models.

    PubMed

    Wentz, Christian T; Oettl, Lars-Lennart; Kelsch, Wolfgang

    2013-10-01

    Optogenetics is the optical control of neuronal excitability by genetically delivered light-activated channels and pumps and represents a promising tool to fuel the study of circuit function in psychiatric animal models. This review highlights three developments. First, we examine the application of optogenetics in one of the neuromodulators central to the pathophysiology of many psychiatric disorders, the dopaminergic system. We then discuss recent work in translating functional magnetic resonance imaging in small animals (in which optogenetics can be employed to reveal physiological mechanisms underlying disease-related alterations in brain circuits) to patients. Finally, we describe emerging technological developments for circuit manipulation in freely behaving animals.

  3. Animal models of trauma-induced coagulopathy.

    PubMed

    Frith, Daniel; Cohen, Mitchell J; Brohi, Karim

    2012-05-01

    Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. A literature review was performed. Structured search of the indexed online database MEDLINE/PubMed in July 2010 identified 43 relevant articles containing 23 distinct animal models of TIC. The main aim of 26 studies was to test a therapeutic and the other 17 were conducted to investigate pathophysiology. A preponderance of porcine models was identified. Three new models demonstrating an endogenous acute traumatic coagulopathy (ATC) have offered new insights into the pathophysiology of TIC. Independent or combined effects of induced hypothermia and metabolic acidosis have been extensively evaluated. Recently, a pig model of TIC has been developed that features all major etiologies of TIC, although not in correct chronological order. This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.

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

    PubMed

    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.

  5. Animal Models of Muscular Dystrophy

    PubMed Central

    Ng, Rainer; Banks, Glen B.; Hall, John K.; Muir, Lindsey A.; Ramos, Julian N.; Wicki, Jacqueline; Odom, Guy L.; Konieczny, Patryk; Seto, Jane; Chamberlain, Joel R.; Chamberlain, Jeffrey S.

    2016-01-01

    The muscular dystrophies (MDs) represent a diverse collection of inherited human disorders, which affect to varying degrees skeletal, cardiac, and sometimes smooth muscle (Emery, 20021). To date, more than 50 different genes have been implicated as causing one or more types of MD (Bansal et al., 20032). In many cases, invaluable insights into disease mechanisms, structure and function of gene products, and approaches for therapeutic interventions have benefited from the study of animal models of the different MDs (Arnett et al., 20093). The large number of genes that are associated with MD and the tremendous number of animal models that have been developed preclude a complete discussion of each in the context of this review. However, we summarize here a number of the more commonly used models together with a mixture of different types of gene and MD, which serves to give a general overview of the value of animal models of MD for research and therapeutic development. PMID:22137430

  6. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  7. Animal models of nephrotic syndrome.

    PubMed

    Simic, Ivana; Tabatabaeifar, Mansoureh; Schaefer, Franz

    2013-11-01

    Animal models of proteinuria and nephrotic syndrome are essential tools for studying the mechanisms of action of abnormalities in individual components of the podocyte and glomerular basement membrane. In recent years a variety of in vivo models have been developed to elucidate the function of specific podocyte proteins and their role in the pathogenesis of proteinuria and glomerulosclerosis. In this overview of the animal models currently available we discuss their contribution to our mechanistic understanding and their potential use in screening for novel targeted therapies of steroid-resistant nephrotic syndrome.

  8. Animal models of diabetes mellitus.

    PubMed

    Rees, D A; Alcolado, J C

    2005-04-01

    Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock-in, generalized knock-out and tissue-specific knockout mice.

  9. Pharmacokinetics of meloxicam in animals and the relevance to humans.

    PubMed

    Busch, U; Schmid, J; Heinzel, G; Schmaus, H; Baierl, J; Huber, C; Roth, W

    1998-06-01

    The pharmacokinetic profile of the new nonsteroidal anti-inflammatory drug meloxicam was investigated in a number of animal species, including mice, rats, dogs, mini-pigs, and baboons, after administration of [14C]meloxicam. The plasma concentration-time profiles for meloxicam in rats and dogs were comparable to that in humans, whereas there were marked differences between humans and mice, mini-pigs, and baboons. The highest tissue concentrations of meloxicam in rats and mini-pigs were seen in the liver and kidneys. In contrast, low concentrations of meloxicam were found in the central nervous system, compared with those in plasma. The excretion balance in mini-pigs resembled that in humans, with almost equal concentrations being eliminated in the urine and the feces. As in humans, meloxicam circulated mainly in the form of the parent compound in the plasma of mice, rats, dogs, mini-pigs, and baboons. The main metabolites in rats, mini-pigs, and humans were a 5'-hydroxymethyl derivative (AF-UH 1 SE) and a 5'-carboxy metabolite (UH-AC 110 SE). The percentage of meloxicam binding to protein was higher in rats and humans (>99%) than in other species. The pharmacokinetic profile of meloxicam in rats most closely resembles that in humans; therefore, reliable clinical predictions can be made from studies in this rodent species.

  10. Small animal models of xenotransplantation.

    PubMed

    Wang, Hao

    2012-01-01

    Organ transplantation has become a successful and acceptable treatment for end-stage organ failure. Such success has allowed transplant patients to resume a normal lifestyle. The demands for transplantation have been steadily increasing, as more patients and new diseases are being deemed eligible for treatment via transplantation. However, it is clear that human organs will never meet the increasing demand of transplantation. Therefore, scientists must continue to pursue alternative therapies and explore new treatments to meet the growing demand for the limited number of organs available. Transplanting organs from animals into humans (xenotransplantation) is one such therapy. The observed enthusiasm for xenotransplantation, irrespective of the severe shortage of human organs and tissues available for transplantation, can be said to stem from at least two factors. First, there is the possibility that animal organs and tissues might be less susceptible than those of humans to the recurrence of disease processes. Second, a xenograft might be used as a vehicle for introducing novel genes or biochemical processes which could be of therapeutic value for the transplant recipient.To date, millions of lives have been saved by organ transplantation. These remarkable achievements would have been impossible without experimental transplantation research in animal models. Presently, more than 95% of organ transplantation research projects are carried out using rodents, such as rats and mice. The key factor to ensure the success of these experiments lies in state-of-the art experimental surgery. Small animal models offer unique advantages for the mechanistic study of xenotransplantation rejection. Currently, multiple models have been developed for investigating the different stages of immunological barriers in xenotransplantation. In this chapter, we describe six valuable small animal models that have been used in xenotransplantation research. The methodology for the small animal

  11. Anhedonia, avolition, and anticipatory deficits: assessments in animals with relevance to the negative symptoms of schizophrenia.

    PubMed

    Barnes, Samuel A; Der-Avakian, Andre; Markou, Athina

    2014-05-01

    Schizophrenia represents a complex, heterogeneous disorder characterized by several symptomatic domains that include positive and negative symptoms and cognitive deficits. Negative symptoms reflect a cluster of symptoms that remains therapeutically unresponsive to currently available medications. Therefore, the development of animal models that may contribute to the discovery of novel and efficacious treatment strategies is essential. An animal model consists of both an inducing condition or manipulation (i.e., independent variable) and an observable measure(s) (i.e., dependent variables) that are used to assess the construct(s) under investigation. The objective of this review is to describe currently available experimental procedures that can be used to characterize constructs relevant to the negative symptoms of schizophrenia in experimental animals. While negative symptoms can encompass aspects of social withdrawal and emotional blunting, this review focuses on the assessment of reward deficits that result in anhedonia, avolition, and abnormal reward anticipation. The development and utilization of animal procedures that accurately assess reward-based constructs related to negative symptomatology in schizophrenia will provide an improved understanding of the neural substrates involved in these processes.

  12. Anhedonia, avolition, and anticipatory deficits: Assessments in animals with relevance to the negative symptoms of schizophrenia

    PubMed Central

    Barnes, Samuel A.; Der-Avakian, Andre; Markou, Athina

    2013-01-01

    Schizophrenia represents a complex, heterogeneous disorder characterized by several symptomatic domains that include positive and negative symptoms, and cognitive deficits. Negative symptoms reflect a cluster of symptoms that remains therapeutically unresponsive to currently available medications. Therefore, the development of animal models that may contribute to the discovery of novel and efficacious treatment strategies is essential. An animal model consists of both an inducing condition or manipulation (i.e., independent variable) and an observable measure(s) (i.e., dependent variables) that are used to assess the construct(s) under investigation. The objective of this review is to describe currently available experimental procedures that can be used to characterize constructs relevant to the negative symptoms of schizophrenia in experimental animals. While negative symptoms can encompass aspects of social withdrawal and emotional blunting, this review focuses on the assessment of reward deficits that result in anhedonia, avolition, and abnormal reward anticipation. The development and utilization of animal procedures that accurately assess reward-based constructs related to negative symptomatology in schizophrenia will provide an improved understanding of the neural substrates involved in these processes. PMID:24183826

  13. Animal models of soft-tissue sarcoma

    PubMed Central

    Dodd, Rebecca D.; Mito, Jeffery K.; Kirsch, David G.

    2010-01-01

    Soft-tissue sarcomas (STSs) are rare mesenchymal tumors that arise from muscle, fat and connective tissue. Currently, over 75 subtypes of STS are recognized. The rarity and heterogeneity of patient samples complicate clinical investigations into sarcoma biology. Model organisms might provide traction to our understanding and treatment of the disease. Over the past 10 years, many successful animal models of STS have been developed, primarily genetically engineered mice and zebrafish. These models are useful for studying the relevant oncogenes, signaling pathways and other cell changes involved in generating STSs. Recently, these model systems have become preclinical platforms in which to evaluate new drugs and treatment regimens. Thus, animal models are useful surrogates for understanding STS disease susceptibility and pathogenesis as well as for testing potential therapeutic strategies. PMID:20713645

  14. Stochastic modelling of animal movement

    PubMed Central

    Smouse, Peter E.; Focardi, Stefano; Moorcroft, Paul R.; Kie, John G.; Forester, James D.; Morales, Juan M.

    2010-01-01

    Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal ‘settling down’, accomplished by including one or more focal points that attract the animal's movements. (ii) Memory-based models are used to predict how accumulated experience translates into biased movement choices, employing reinforced random walk behaviour, with previous visitation increasing or decreasing the probability of repetition. (iii) Lévy movement involves a step-length distribution that is over-dispersed, relative to standard probability distributions, and adaptive in exploring new environments or searching for rare targets. Each of these modelling arenas implies more detail in the movement pattern than general models of movement can accommodate, but realistic empiric evaluation of their predictions requires dense locational data, both in time and space, only available with modern GPS telemetry. PMID:20566497

  15. Animal models of Alzheimer disease.

    PubMed

    LaFerla, Frank M; Green, Kim N

    2012-11-01

    Significant insights into the function of genes associated with Alzheimer disease and related dementias have occurred through studying genetically modified animals. Although none of the existing models fully reproduces the complete spectrum of this insidious human disease, critical aspects of Alzheimer pathology and disease processes can be experimentally recapitulated. Genetically modified animal models have helped advance our understanding of the underlying mechanisms of disease and have proven to be invaluable in the preclinical evaluation of potential therapeutic interventions. Continuing refinement and evolution to yield the next generation of animal models will facilitate successes in producing greater translational concordance between preclinical studies and human clinical trials and eventually lead to the introduction of novel therapies into clinical practice.

  16. Animal models of cardiovascular diseases.

    PubMed

    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.

  17. Animal models in virus research: their utility and limitations.

    PubMed

    Louz, Derrick; Bergmans, Hans E; Loos, Birgit P; Hoeben, Rob C

    2013-11-01

    Viral diseases are important threats to public health worldwide. With the number of emerging viral diseases increasing the last decades, there is a growing need for appropriate animal models for virus studies. The relevance of animal models can be limited in terms of mimicking human pathophysiology. In this review, we discuss the utility of animal models for studies of influenza A viruses, HIV and SARS-CoV in light of viral emergence, assessment of infection and transmission risks, and regulatory decision making. We address their relevance and limitations. The susceptibility, immune responses, pathogenesis, and pharmacokinetics may differ between the various animal models. These complexities may thwart translating results from animal experiments to the humans. Within these constraints, animal models are very informative for studying virus immunopathology and transmission modes and for translation of virus research into clinical benefit. Insight in the limitations of the various models may facilitate further improvements of the models.

  18. Small mammalian animal models of heart disease

    PubMed Central

    Camacho, Paula; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang

    2016-01-01

    There is an urgent clinical need to develop new therapeutic approaches for treating cardiovascular disease, but the biology of cardiovascular regeneration is complex. Model systems are required to advance our understanding of the pathogenesis, progression, and mechanisms underlying cardiovascular disease as well as to test therapeutic approaches to regenerate tissue and restore cardiac function following injury. An ideal model system should be inexpensive, easily manipulated, reproducible, physiologically representative of human disease, and ethically sound. The choice of animal model needs to be considered carefully since it affects experimental outcomes and whether findings of the study can be reasonably translated to humans. This review presents a guideline for the commonly used small animal models (mice, rats, rabbits, and cats) used in cardiac research as an effort to standardize the most relevant procedures and obtain translatable and reproducible results. PMID:27679742

  19. Bridging Animal and Human Models

    PubMed Central

    Barkley-Levenson, Amanda M.; Crabbe, John C.

    2012-01-01

    Genetics play an important role in the development and course of alcohol abuse, and understanding genetic contributions to this disorder may lead to improved preventative and therapeutic strategies in the future. Studies both in humans and in animal models are necessary to fully understand the neurobiology of alcoholism from the molecular to the cognitive level. By dissecting the complex facets of alcoholism into discrete, well-defined phenotypes that are measurable in both human populations and animal models of the disease, researchers will be better able to translate findings across species and integrate the knowledge obtained from various disciplines. Some of the key areas of alcoholism research where consilience between human and animal studies is possible are alcohol withdrawal severity, sensitivity to rewards, impulsivity, and dysregulated alcohol consumption. PMID:23134048

  20. Animal Models of Zika Virus.

    PubMed

    P Bradley And Claude M Nagamine, Michael

    2017-03-07

    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.

  1. An ecologist's guide to the animal model.

    PubMed

    Wilson, Alastair J; Réale, Denis; Clements, Michelle N; Morrissey, Michael M; Postma, Erik; Walling, Craig A; Kruuk, Loeske E B; Nussey, Daniel H

    2010-01-01

    1. Efforts to understand the links between evolutionary and ecological dynamics hinge on our ability to measure and understand how genes influence phenotypes, fitness and population dynamics. Quantitative genetics provides a range of theoretical and empirical tools with which to achieve this when the relatedness between individuals within a population is known. 2. A number of recent studies have used a type of mixed-effects model, known as the animal model, to estimate the genetic component of phenotypic variation using data collected in the field. Here, we provide a practical guide for ecologists interested in exploring the potential to apply this quantitative genetic method in their research. 3. We begin by outlining, in simple terms, key concepts in quantitative genetics and how an animal model estimates relevant quantitative genetic parameters, such as heritabilities or genetic correlations. 4. We then provide three detailed example tutorials, for implementation in a variety of software packages, for some basic applications of the animal model. We discuss several important statistical issues relating to best practice when fitting different kinds of mixed models. 5. We conclude by briefly summarizing more complex applications of the animal model, and by highlighting key pitfalls and dangers for the researcher wanting to begin using quantitative genetic tools to address ecological and evolutionary questions.

  2. Animal to human translational paradigms relevant for approach avoidance conflict decision making.

    PubMed

    Kirlic, Namik; Young, Jared; Aupperle, Robin L

    2017-09-01

    Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. [Relevance of mycotoxin contaminated feed for farm animals and carryover of mycotoxins to food of animal origin].

    PubMed

    Gareis, M; Wolff, J

    2000-01-01

    Contaminated feed is the main source for mycotoxin infestation of farm animals. The oral intake of fungal metabolites with feed results in a negative impact on all relevant parameters of animal production. Moreover, under experimental conditions mycotoxins and/or their metabolites can be traced in meat, edible tissues, milk and eggs. However due to the high concentrations of toxins involved, such findings are rare in the daily practice. In Germany today only aflatoxins (aflatoxin M1 in milk) and ochratoxin A (in blood, meat and edible tissues from swine) are of practical relevance from the view of food hygiene and food safety. Other mycotoxins at present discussed like toxins of Fusaria (trichothecenes, zearaleone, fumonisins) and ergot alkaloids are of no importance as possible contaminants in food from animal origin although they could have a negative impact on animal production.

  4. Animal models for auditory streaming.

    PubMed

    Itatani, Naoya; Klump, Georg M

    2017-02-19

    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'.

  5. Animal models of polymicrobial pneumonia

    PubMed Central

    Hraiech, Sami; Papazian, Laurent; Rolain, Jean-Marc; Bregeon, Fabienne

    2015-01-01

    Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although “two hits” animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information. PMID:26170617

  6. Large genetic animal models of Huntington's Disease.

    PubMed

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.

  7. Morally relevant differences between animals and human beings justifying the use of animals in biomedical research.

    PubMed

    Dennis, J U

    1997-03-01

    I have attempted to show that the differential qualities of animals and human beings indeed to have bearing on moral rules and the derivation of rights, including rights established on the basis of reason and utilitarianism. Special rights for members of our species are not simply a consequence of human domination and self-interest. I also have tried to show that rights arise from values and that the qualities we value most highly often are the ones that distinguish human beings from other species. I maintain that giving more value to human lives over animal lives achieves reflective balance with the commonsense notions that most of us have developed. Because utilitarianism, contractualism, and the classical philosophical methods of Kant and Aristotle all may allow favoring human interests over animal interests, it seems reasonable to suspect that animal rights activists embrace narrow, extremist views. There are many uniquely human experiences to which we ascribe high value-deep interpersonal relationships, achieving a life's goal, enjoying a complex cultural event such as a play or an opera, or authoring a manuscript. Therefore, it would seem improper that social and ethical considerations regarding animals be centered entirely on the notion of a biological continuum, because there are many kinds of human experience-moral, religious, aesthetic, and otherwise-that appear to be outside the realm of biology. Knowledge about the biology of animals is helpful for making moral decisions about our obligations to them. Why, then, is there a substantial population of animal rights activists in Europe, the United States, and throughout the world, who would not agree with my conclusions? Certain habitual ways of thinking may encourage anthropomorphism and equating animal interests with human interests. Certain metaphysical beliefs, such as a belief in reincarnation, also might favor animal rights. It also is possible that a number of people are being deceived and misled by

  8. Animal models of papillomavirus pathogenesis.

    PubMed

    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

  9. Comparative biology of cystic fibrosis animal models.

    PubMed

    Fisher, John T; Zhang, Yulong; Engelhardt, John F

    2011-01-01

    Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

  10. Animal models of source memory.

    PubMed

    Crystal, Jonathon D

    2016-01-01

    Source memory is the aspect of episodic memory that encodes the origin (i.e., source) of information acquired in the past. Episodic memory (i.e., our memories for unique personal past events) typically involves source memory because those memories focus on the origin of previous events. Source memory is at work when, for example, someone tells a favorite joke to a person while avoiding retelling the joke to the friend who originally shared the joke. Importantly, source memory permits differentiation of one episodic memory from another because source memory includes features that were present when the different memories were formed. This article reviews recent efforts to develop an animal model of source memory using rats. Experiments are reviewed which suggest that source memory is dissociated from other forms of memory. The review highlights strengths and weaknesses of a number of animal models of episodic memory. Animal models of source memory may be used to probe the biological bases of memory. Moreover, these models can be combined with genetic models of Alzheimer's disease to evaluate pharmacotherapies that ultimately have the potential to improve memory.

  11. Animal models of drug addiction.

    PubMed

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

    2017-01-12

    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.

  12. Overcrowding and Population Growth: The Nature and Relevance of Animal Behavior.

    ERIC Educational Resources Information Center

    Stettner, Laurence J.

    This paper provides a descriptive overview of research on the consequences of overcrowding and the development of high population densities in animals, and speculates on the relevance of these studies for similar human phenomena. Three major foci are distinguished: (1) the effect of high population densities on animal behavior; (2) the nature of…

  13. Henipavirus infections: lessons from animal models.

    PubMed

    Dhondt, Kévin P; Horvat, Branka

    2013-04-09

    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. Henipavirus Infections: Lessons from Animal Models

    PubMed Central

    Dhondt, Kévin P.; Horvat, Branka

    2013-01-01

    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. PMID:25437037

  15. Animal models of cognitive dysfunction.

    PubMed

    Tayebati, Seyed Khosrow

    2006-02-01

    The increased life expectancy in industrialised countries in the last half century has also brought to a greater incidence of neurological disorders, including neurodegenerative diseases and developing in a rather long time. In this respect, Alzheimer's disease (AD), for the large incidence, and the dramatic loss of autonomy caused by its cognitive and behavioural symptoms represents one of the main challenges of modern medicine. Although AD is a typical human disease and probably includes several nosographic entities, the use of animal models may contribute to understand specific aspects of pathophysiology of the disease. The most widely used animal models are rodents and non-human primates. In this review different animal models characterised by impaired cognitive functions are analysed. None of the models available mimics exactly cognitive, behavioural, biochemical and histopathological abnormalities observed in neurological disorders characterised by cognitive impairment. However, partial reproduction of neuropathology and/or cognitive deficits of Alzheimer's disease (AD), vascular dementia and dementia occurring in Huntington's and Parkinson's diseases, or in other neurodegenerative disorders may represent a basis for understanding pathophysiological traits of these diseases and for contributing to their treatments.

  16. Experimental animal models of osteonecrosis.

    PubMed

    Fan, Meng; Peng, Jiang; Qin, Ling; Lu, Shibi

    2011-08-01

    Osteonecrosis (ON) or avascular necrosis (AVN) is a common bone metabolic disorder, mostly affecting femoral head. Although many biological, biophysical, and surgical methods have been tested to preserve the femoral head with ON, none has been proven fully satisfactory. It lacks consensus on an optimal approach for treatment. This is due, at least in part, to the lack of ability to systematically compare treatment efficacy using an ideal animal model that mimics full-range osteonecrosis of femoral head (ONFH) in humans with high incidence of joint collapse accompanied by reparative reaction adjacent to the necrotic bone in a reproducible and accessible way. A number of preclinical animal ON models have been established for testing potential efficacy of various modalities developed for prevention and treatment of ON before introduction into clinics for potential applications. This paper describes a number of different methods for creating animal experimental ON models. Advantages and disadvantages of such models are also discussed as reference for future research in battle against this important medical condition.

  17. Evaluation of Surrogate Animal Models of Melioidosis

    PubMed Central

    Warawa, Jonathan Mark

    2010-01-01

    Burkholderia pseudomallei is the Gram-negative bacterial pathogen responsible for the disease melioidosis. B. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. B. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant models including mammalian and invertebrate hosts. This review seeks to summarize published findings related to established animal models of melioidosis, with an aim to compare and contrast the virulence of B. pseudomallei in these models. The effect of the route of delivery on disease is also discussed for intravenous, intraperitoneal, subcutaneous, intranasal, aerosol, oral, and intratracheal infection methodologies, with a particular focus on how they relate to modeling clinical melioidosis. The importance of the translational validity of the animal models used in B. pseudomallei research is highlighted as these studies have become increasingly therapeutic in nature. PMID:21772830

  18. Phenotypic variation in metabolism and morphology correlating with animal swimming activity in the wild: relevance for the OCLTT (oxygen- and capacity-limitation of thermal tolerance), allocation and performance models

    PubMed Central

    Baktoft, Henrik; Jacobsen, Lene; Skov, Christian; Koed, Anders; Jepsen, Niels; Berg, Søren; Boel, Mikkel; Aarestrup, Kim; Svendsen, Jon C.

    2016-01-01

    Ongoing climate change is affecting animal physiology in many parts of the world. Using metabolism, the oxygen- and capacity-limitation of thermal tolerance (OCLTT) hypothesis provides a tool to predict the responses of ectothermic animals to variation in temperature, oxygen availability and pH in the aquatic environment. The hypothesis remains controversial, however, and has been questioned in several studies. A positive relationship between aerobic metabolic scope and animal activity would be consistent with the OCLTT but has rarely been tested. Moreover, the performance model and the allocation model predict positive and negative relationships, respectively, between standard metabolic rate and activity. Finally, animal activity could be affected by individual morphology because of covariation with cost of transport. Therefore, we hypothesized that individual variation in activity is correlated with variation in metabolism and morphology. To test this prediction, we captured 23 wild European perch (Perca fluviatilis) in a lake, tagged them with telemetry transmitters, measured standard and maximal metabolic rates, aerobic metabolic scope and fineness ratio and returned the fish to the lake to quantify individual in situ activity levels. Metabolic rates were measured using intermittent flow respirometry, whereas the activity assay involved high-resolution telemetry providing positions every 30 s over 12 days. We found no correlation between individual metabolic traits and activity, whereas individual fineness ratio correlated with activity. Independent of body length, and consistent with physics theory, slender fish maintained faster mean and maximal swimming speeds, but this variation did not result in a larger area (in square metres) explored per 24 h. Testing assumptions and predictions of recent conceptual models, our study indicates that individual metabolism is not a strong determinant of animal activity, in contrast to individual morphology, which is

  19. Animal models of serotonergic psychedelics.

    PubMed

    Hanks, James B; González-Maeso, Javier

    2013-01-16

    The serotonin 5-HT(2A) receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest behavioral abnormalities elicited by psychedelics in rodents that predict such effects in humans. Here we review the behavioral effects induced by psychedelic drugs in rodent models, discuss the translational potential of these findings, and define areas where further research is needed to better understand the molecular mechanisms and neuronal circuits underlying their neuropsychological effects.

  20. Animal Models of Serotonergic Psychedelics

    PubMed Central

    2012-01-01

    The serotonin 5-HT2A receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest behavioral abnormalities elicited by psychedelics in rodents that predict such effects in humans. Here we review the behavioral effects induced by psychedelic drugs in rodent models, discuss the translational potential of these findings, and define areas where further research is needed to better understand the molecular mechanisms and neuronal circuits underlying their neuropsychological effects. PMID:23336043

  1. Software Validation via Model Animation

    NASA Technical Reports Server (NTRS)

    Dutle, Aaron M.; Munoz, Cesar A.; Narkawicz, Anthony J.; Butler, Ricky W.

    2015-01-01

    This paper explores a new approach to validating software implementations that have been produced from formally-verified algorithms. Although visual inspection gives some confidence that the implementations faithfully reflect the formal models, it does not provide complete assurance that the software is correct. The proposed approach, which is based on animation of formal specifications, compares the outputs computed by the software implementations on a given suite of input values to the outputs computed by the formal models on the same inputs, and determines if they are equal up to a given tolerance. The approach is illustrated on a prototype air traffic management system that computes simple kinematic trajectories for aircraft. Proofs for the mathematical models of the system's algorithms are carried out in the Prototype Verification System (PVS). The animation tool PVSio is used to evaluate the formal models on a set of randomly generated test cases. Output values computed by PVSio are compared against output values computed by the actual software. This comparison improves the assurance that the translation from formal models to code is faithful and that, for example, floating point errors do not greatly affect correctness and safety properties.

  2. Animal models of Wilson disease.

    PubMed

    Medici, Valentina; Huster, Dominik

    2017-01-01

    Wilson disease (WD) is caused by ATPase copper-transporting beta (ATP7B) mutations and results in copper toxicity in liver and brain. Although the defective gene was identified in 1993, the specific mechanisms underlying copper toxicity and the remarkable phenotypic diversity of the disease are still poorly understood. Animal models harboring defects in the ATP7B homolog have helped to reveal new insights into pathomechanisms of WD. Four rodent models with ATP7B gene defects have been described - the Long-Evans Cinnamon (LEC) rat, inbred mouse models (toxic milk (tx), the Jackson Laboratory toxic milk (tx-j)), and the genetically engineered ATP7B(-/-) (knockout) mouse - all of which develop liver disease to different extents. Copper accumulation in parts of the brain accompanied by some neurologic involvement was revealed in LEC rats and tx/tx-j mice, but the pathology is less severe than human neurologic WD. Several dogs show hepatic copper toxicity resembling WD; however, brain involvement has not been observed and the underlying genetic defect is different. These models are of great value for examination of copper distribution and metabolism, gene expression, and investigation of liver and brain pathology. The availability of disease models is essential for therapeutic interventions such as drug, gene, and cell therapy. Findings made by animal studies may facilitate the development of specific therapies to ameliorate WD progression. © 2017 Elsevier B.V. All rights reserved.

  3. Animal Models in Pressure Ulcer Research

    PubMed Central

    Salcido, Richard; Popescu, Adrian; Ahn, Chulhyun

    2007-01-01

    Background/Objective: Research targeting the pathophysiology, prevention, and treatment of pressure ulcers (PrUs) continue to be a significant priority for clinical and basic science research. Spinal cord injury patients particularly benefit from PrU research, because the prevalence of chronic wounds in this category is increasing despite standardized medical care. Because of practical, ethical, and safety considerations, PrUs in the human environment are limited to studies involving patients with pre-existing ulcers. Therefore, we are limited in our basic knowledge pertaining to the development, progression, and healing environment in this devastating disease. Methods: This review provides a synopsis of literature and a discussion of techniques used to induce PrUs in animal models. The question of what animal model best mimics the human PrU environment has been a subject of debate by investigators, peer review panels, and editors. The similarities in wound development and healing in mammalian tissue make murine models a relevant model for understanding the causal factors as well as the wound healing elements. Although we are beginning to understand some of the mechanisms of PrU development, a key dilemma of what makes an apparently healthy tissue develop a PrU waits to be solved. Results and Conclusions: No single method of induction and exploring PrUs in animals can address all the aspects of the pathology of chronic wounds. Each model has its particular strengths and weaknesses. Certain types of models can selectively identify specific aspects of wound development, quantify the extent of lesions, and assess outcomes from interventions. The appropriate interpretation of these methods is significant for proper study design, an understanding of the results, and extrapolation to clinical relevance. PMID:17591222

  4. [Animal models of cardiovascular disease].

    PubMed

    Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente

    2009-01-01

    The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.

  5. Animal models of rheumatoid arthritis: How informative are they?

    PubMed

    McNamee, Kay; Williams, Richard; Seed, Michael

    2015-07-15

    Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.

  6. Translational Relevance of Swine Models of Spinal Cord Injury.

    PubMed

    Schomberg, Dominic T; Miranpuri, Gurwattan S; Chopra, Abhishek; Patel, Kush; Meudt, Jennifer J; Tellez, Armando; Resnick, Daniel K; Shanmuganayagam, Dhanansayan

    2017-02-01

    Spinal cord injury (SCI) is a physically and psychologically devastating clinical condition. The typical treatment regimens of decompressive surgery and rehabilitation therapy still leave many patients with permanent disability. The development of new therapies and devices can be accelerated if relevant translational animal models are more effectively used in pre-clinical stages. Swine is a highly relevant model for SCI research, especially with respect to spine and spinal cord anatomy, spine vasculature, immune responses to injury, and functional assessments. Several spine injury models have recently been developed for swine and are beginning to be used to evaluate new therapies. Swine models of SCI offer tremendous advantages for efficient translation of pre-clinical discoveries and the development of new therapies and devices. Future swine models will also be enhanced by advances in gene-editing technology to further elucidate the complex pathophysiology associated with SCI and provide a means to engineer specific spinal pathologies.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:28298815

  9. Towards increased policy relevance in energy modeling

    SciTech Connect

    Worrell, Ernst; Ramesohl, Stephan; Boyd, Gale

    2003-07-29

    Historically, most energy models were reasonably equipped to assess the impact of a subsidy or change in taxation, but are often insufficient to assess the impact of more innovative policy instruments. We evaluate the models used to assess future energy use, focusing on industrial energy use. We explore approaches to engineering-economic analysis that could help improve the realism and policy relevance of engineering-economic modeling frameworks. We also explore solutions to strengthen the policy usefulness of engineering-economic analysis that can be built from a framework of multi-disciplinary cooperation. We focus on the so-called ''engineering-economic'' (or ''bottom-up'') models, as they include the amount of detail that is commonly needed to model policy scenarios. We identify research priorities for the modeling framework, technology representation in models, policy evaluation and modeling of decision-making behavior.

  10. A step-by-step guide to systematically identify all relevant animal studies

    PubMed Central

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

  11. An animal model of fetishism.

    PubMed

    Köksal, Falih; Domjan, Michael; Kurt, Adnan; Sertel, Ozlem; Orüng, Sabiha; Bowers, Rob; Kumru, Gulsen

    2004-12-01

    An animal model of sexual fetishism was developed with male Japanese quail based on persistence of conditioned sexual responding during extinction to an inanimate object made of terrycloth (Experiments 1 and 3). This persistent responding occurred only in subjects that came to copulate with the terrycloth object, suggesting that the copulatory behavior served to maintain the fetishistic behavior. Sexual conditioning was carried out by pairing a conditioned stimulus (CS) with the opportunity to copulate with a female (the unconditioned stimulus or US). Copulation with the CS object and persistent responding did not develop if the CS was a light (Experiment 1) or if conditioning was carried out with a food US (Experiment 2). In addition, subjects that showed persistence in responding to the terrycloth CS did not persist in their responding to a light CS (Experiment 3). The results are consistent with the hypothesis that conditioned copulatory behavior creates a form of self-maintenance that leads to persistent responding to an inanimate object. The development of an animal model of such fetishistic behavior should facilitate experimental analysis of the phenomenon.

  12. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  13. Animal models and conserved processes

    PubMed Central

    2012-01-01

    Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is insufficient for inter

  14. Autism spectrum disorder: neuropathology and animal models.

    PubMed

    Varghese, Merina; Keshav, Neha; Jacot-Descombes, Sarah; Warda, Tahia; Wicinski, Bridget; Dickstein, Dara L; Harony-Nicolas, Hala; De Rubeis, Silvia; Drapeau, Elodie; Buxbaum, Joseph D; Hof, Patrick R

    2017-06-05

    Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each. Postmortem examination of ASD brains has revealed global changes including disorganized gray and white matter, increased number of neurons, decreased volume of neuronal soma, and increased neuropil, the last reflecting changes in densities of dendritic spines, cerebral vasculature and glia. Both cortical and non-cortical areas show region-specific abnormalities in neuronal morphology and cytoarchitectural organization, with consistent findings reported from the prefrontal cortex, fusiform gyrus, frontoinsular cortex, cingulate cortex, hippocampus, amygdala, cerebellum and brainstem. The paucity of postmortem human studies linking neuropathology to the underlying etiology has been partly addressed using animal models to explore the impact of genetic and non-genetic factors clinically relevant for the ASD phenotype. Genetically modified models include those based on well-studied monogenic ASD genes (NLGN3, NLGN4, NRXN1, CNTNAP2, SHANK3, MECP2, FMR1, TSC1/2), emerging risk genes (CHD8, SCN2A, SYNGAP1, ARID1B, GRIN2B, DSCAM, TBR1), and copy number variants (15q11-q13 deletion, 15q13.3 microdeletion, 15q11-13 duplication, 16p11.2 deletion and duplication, 22q11.2 deletion). Models of idiopathic ASD include inbred rodent strains that mimic ASD behaviors as well as models developed by environmental interventions such as prenatal exposure to sodium valproate, maternal autoantibodies, and maternal immune activation. In addition to replicating some of the

  15. Animal Models of Diabetic Retinopathy.

    PubMed

    Olivares, Ana Maria; Althoff, Kristen; Chen, Gloria Fanghua; Wu, Siqi; Morrisson, Margaux A; DeAngelis, Margaret M; Haider, Neena

    2017-08-24

    Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.

  16. Systematic Review of Traumatic Brain Injury Animal Models.

    PubMed

    Phipps, Helen W

    2016-01-01

    The goals of this chapter are to provide an introduction into the variety of animal models available for studying traumatic brain injury (TBI) and to provide a concise systematic review of the general materials and methods involved in each model. Materials and methods were obtained from a literature search of relevant peer-reviewed articles. Strengths and weaknesses of each animal choice were presented to include relative cost, anatomical and physiological features, and mechanism of injury desired. Further, a variety of homologous, isomorphic/induced, and predictive animal models were defined, described, and compared with respect to their relative ease of use, characteristics, range, adjustability (e.g., amplitude, duration, mass/size, velocity, and pressure), and rough order of magnitude cost. Just as the primary mechanism of action of TBI is limitless, so are the animal models available to study TBI. With such a wide variety of available animals, types of injury models, along with the research needs, there exists no single "gold standard" model of TBI rendering cross-comparison of data extremely difficult. Therefore, this chapter reflects a representative sampling of the TBI animal models available and is not an exhaustive comparison of every possible model and associated parameters. Throughout this chapter, special considerations for animal choice and TBI animal model classification are discussed. Criteria central to choosing appropriate animal models of TBI include ethics, funding, complexity (ease of use, safety, and controlled access requirements), type of model, model characteristics, and range of control (scope).

  17. Decompression models: review, relevance and validation capabilities.

    PubMed

    Hugon, J

    2014-01-01

    For more than a century, several types of mathematical models have been proposed to describe tissue desaturation mechanisms in order to limit decompression sickness. These models are statistically assessed by DCS cases, and, over time, have gradually included bubble formation biophysics. This paper proposes to review this evolution and discuss its limitations. This review is organized around the comparison of decompression model biophysical criteria and theoretical foundations. Then, the DCS-predictive capability was analyzed to assess whether it could be improved by combining different approaches. Most of the operational decompression models have a neo-Haldanian form. Nevertheless, bubble modeling has been gaining popularity, and the circulating bubble amount has become a major output. By merging both views, it seems possible to build a relevant global decompression model that intends to simulate bubble production while predicting DCS risks for all types of exposures and decompression profiles. A statistical approach combining both DCS and bubble detection databases has to be developed to calibrate a global decompression model. Doppler ultrasound and DCS data are essential: i. to make correlation and validation phases reliable; ii. to adjust biophysical criteria to fit at best the observed bubble kinetics; and iii. to build a relevant risk function.

  18. Parathyroid diseases and animal models.

    PubMed

    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.

  19. Animal models of recurrent or bipolar depression.

    PubMed

    Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K

    2016-05-03

    Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques.

  20. Modeling autistic features in animals.

    PubMed

    Patterson, Paul H

    2011-05-01

    A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASDs) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, and alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis, and early progress toward clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than to primary articles.

  1. Animal Models of Williams Syndrome

    PubMed Central

    OSBORNE, LUCY R.

    2010-01-01

    In recent years, researchers have generated a variety of mouse models in an attempt to dissect the contribution of individual genes to the complex phenotype associated with Williams syndrome (WS). The mouse genome is easily manipulated to produce animals that are copies of humans with genetic conditions, be it with null mutations, hypomorphic mutations, point mutations, or even large deletions encompassing many genes. The existing mouse models certainly seem to implicate hemizygosity for ELN, BAZ1B, CLIP2, and GTF2IRD1 in WS, and new mice with large deletions of the WS region are helping us to understand both the additive and potential combinatorial effects of hemizygosity for specific genes. However, not all genes that are haploinsufficient in humans prove to be so in mice and the effect of genetic background can also have a significant effect on the penetrance of many phenotypes. Thus although mouse models are powerful tools, the information garnered from their study must be carefully interpreted. Nevertheless, mouse models look set to provide a wealth of information about the neuroanatomy, neurophysiology and molecular pathways that underlie WS and in the future will act as essential tools for the development and testing of therapeutics. PMID:20425782

  2. Animal models of Williams syndrome.

    PubMed

    Osborne, Lucy R

    2010-05-15

    In recent years, researchers have generated a variety of mouse models in an attempt to dissect the contribution of individual genes to the complex phenotype associated with Williams syndrome (WS). The mouse genome is easily manipulated to produce animals that are copies of humans with genetic conditions, be it with null mutations, hypomorphic mutations, point mutations, or even large deletions encompassing many genes. The existing mouse models certainly seem to implicate hemizygosity for ELN, BAZ1B, CLIP2, and GTF2IRD1 in WS, and new mice with large deletions of the WS region are helping us to understand both the additive and potential combinatorial effects of hemizygosity for specific genes. However, not all genes that are haploinsufficient in humans prove to be so in mice and the effect of genetic background can also have a significant effect on the penetrance of many phenotypes. Thus although mouse models are powerful tools, the information garnered from their study must be carefully interpreted. Nevertheless, mouse models look set to provide a wealth of information about the neuroanatomy, neurophysiology and molecular pathways that underlie WS and in the future will act as essential tools for the development and testing of therapeutics.

  3. Modeling Autistic Features in Animals

    PubMed Central

    Patterson, Paul H.

    2011-01-01

    A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASD) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, as well as alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis and early progress towards clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than primary articles. PMID:21289542

  4. Animal model of neuropathic tachycardia syndrome

    NASA Technical Reports Server (NTRS)

    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.

  5. Companion animals symposium: humanized animal models of the microbiome.

    PubMed

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

    Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

  6. Large animal models of traumatic brain injury.

    PubMed

    Dai, Jun-Xi; Ma, Yan-Bin; Le, Nan-Yang; Cao, Jun; Wang, Yang

    2017-10-03

    Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. Mixed published articles and books associated with large animal models of TBI were researched and summarized. We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

  7. Ethological concepts enhance the translational value of animal models.

    PubMed

    Peters, Suzanne M; Pothuizen, Helen H J; Spruijt, Berry M

    2015-07-15

    The translational value of animal models is an issue of ongoing discussion. We argue that 'Refinement' of animal experiments is needed and this can be achieved by exploiting an ethological approach when setting up and conducting experiments. Ethology aims to assess the functional meaning of behavioral changes, due to experimental manipulation or treatment, in animal models. Although the use of ethological concepts is particularly important for studies involving the measurement of animal behavior (as is the case for most studies on neuro-psychiatric conditions), it will also substantially benefit other disciplines, such as those investigating the immune system or inflammatory response. Using an ethological approach also involves using more optimal testing conditions are employed that have a biological relevance to the animal. Moreover, using a more biological relevant analysis of the data will help to clarify the functional meaning of the modeled readout (e.g. whether it is psychopathological or adaptive in nature). We advocate for instance that more behavioral studies should use animals in group-housed conditions, including the recording of their ultrasonic vocalizations, because (1) social behavior is an essential feature of animal models for human 'social' psychopathologies, such as autism and schizophrenia, and (2) social conditions are indispensable conditions for appropriate behavioral studies in social species, such as the rat. Only when taking these elements into account, the validity of animal experiments and, thus, the translation value of animal models can be enhanced.

  8. Serotonergic Hallucinogens as Translational Models Relevant to Schizophrenia

    PubMed Central

    Halberstadt, Adam L.; Geyer, Mark A.

    2014-01-01

    One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT2A receptor. These compounds produce a “model psychosis” in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioral effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects, and their translational relevance. Despite the difficulty of modeling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents. PMID:23942028

  9. Serotonergic hallucinogens as translational models relevant to schizophrenia.

    PubMed

    Halberstadt, Adam L; Geyer, Mark A

    2013-11-01

    One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT(2A) receptor. These compounds produce a 'model psychosis' in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioural effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects and their translational relevance. Despite the difficulty of modelling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents.

  10. Animal Models of Stress Urinary Incontinence

    PubMed Central

    Jiang, Hai-Hong

    2011-01-01

    Stress urinary incontinence (SUI) is a common health problem significantly affecting the quality of life of women worldwide. Animal models that simulate SUI enable the assessment of the mechanism of risk factors for SUI in a controlled fashion, including childbirth injuries, and enable preclinical testing of new treatments and therapies for SUI. Animal models that simulate childbirth are presently being utilized to determine the mechanisms of the maternal injuries of childbirth that lead to SUI with the goal of developing prophylactic treatments. Methods of assessing SUI in animals that mimic diagnostic methods used clinically have been developed to evaluate the animal models. Use of these animal models to test innovative treatment strategies has the potential to improve clinical management of SUI. This chapter provides a review of the available animal models of SUI, as well as a review of the methods of assessing SUI in animal models, and potential treatments that have been tested on these models. PMID:21290221

  11. [Research advances in animal models of intervertebral disc degeneration].

    PubMed

    Zhang, Wenli; Liu, Hao; Li, Tanzhu

    2007-11-01

    To review the research advances in animal models of human disc degeneration. The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.

  12. Mathematical modeling relevant to closed artificial ecosystems

    USGS Publications Warehouse

    DeAngelis, D.L.

    2003-01-01

    The mathematical modeling of ecosystems has contributed much to the understanding of the dynamics of such systems. Ecosystems can include not only the natural variety, but also artificial systems designed and controlled by humans. These can range from agricultural systems and activated sludge plants, down to mesocosms, microcosms, and aquaria, which may have practical or research applications. Some purposes may require the design of systems that are completely closed, as far as material cycling is concerned. In all cases, mathematical modeling can help not only to understand the dynamics of the system, but also to design methods of control to keep the system operating in desired ranges. This paper reviews mathematical modeling relevant to the simulation and control of closed or semi-closed artificial ecosystems designed for biological production and recycling in applications in space. Published by Elsevier Science Ltd on behalf of COSPAR.

  13. Mathematical modeling relevant to closed artificial ecosystems.

    PubMed

    DeAngelis, Donald L

    2003-01-01

    The mathematical modeling of ecosystems has contributed much to the understanding of the dynamics of such systems. Ecosystems can include not only the natural variety, but also artificial systems designed and controlled by humans. These can range from agricultural systems and activated sludge plants, down to mesocosms, microcosms, and aquaria, which may have practical or research applications. Some purposes may require the design of systems that are completely closed, as far as material cycling is concerned. In all cases, mathematical modeling can help not only to understand the dynamics of the system, but also to design methods of control to keep the system operating in desired ranges. This paper reviews mathematical modeling relevant to the simulation and control of closed or semi-closed artificial ecosystems designed for biological production and recycling in applications in space.

  14. Potency of Animal Models in KANSEI Engineering

    NASA Astrophysics Data System (ADS)

    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.

  15. Chronobiology of ethanol: animal models.

    PubMed

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders.

  16. Logical fallacies in animal model research.

    PubMed

    Sjoberg, Espen A

    2017-02-15

    Animal models of human behavioural deficits involve conducting experiments on animals with the hope of gaining new knowledge that can be applied to humans. This paper aims to address risks, biases, and fallacies associated with drawing conclusions when conducting experiments on animals, with focus on animal models of mental illness. Researchers using animal models are susceptible to a fallacy known as false analogy, where inferences based on assumptions of similarities between animals and humans can potentially lead to an incorrect conclusion. There is also a risk of false positive results when evaluating the validity of a putative animal model, particularly if the experiment is not conducted double-blind. It is further argued that animal model experiments are reconstructions of human experiments, and not replications per se, because the animals cannot follow instructions. This leads to an experimental setup that is altered to accommodate the animals, and typically involves a smaller sample size than a human experiment. Researchers on animal models of human behaviour should increase focus on mechanistic validity in order to ensure that the underlying causal mechanisms driving the behaviour are the same, as relying on face validity makes the model susceptible to logical fallacies and a higher risk of Type 1 errors. We discuss measures to reduce bias and risk of making logical fallacies in animal research, and provide a guideline that researchers can follow to increase the rigour of their experiments.

  17. Small Animal In Vivo X-Ray Tomosynthesis: Anatomical Relevance of the Reconstructed Images.

    PubMed

    Barquero, H; Brasse, D

    2016-02-01

    Whole body X-ray micro-Digital Tomosynthesis (micro-DT) for small animal imaging is introduced in this work. Such a system allows to deal with geometrical constraints that do not allow to use a micro-CT system as well as to reduce the radiological dose compared to a micro-CT scan. Data was simulated using the Digimouse anatomical model of the mouse with the designed system. An algebraic reconstruction algorithm regularized by Total Variation norm (TV) minimization was used to reconstruct images. Parameters for the reconstruction were optimized and the algorithm performance was evaluated quantitatively. High contrast tissues were subsequently segmented by thresholding the image. Quantitative analysis of the segmented domains indicates that a relevant anatomical information can possibly be extracted from micro-DT images. Indeed the Dice's coefficient values are greater than 0.8 for the segmented High Contrast Tissues compared to the phantom, which indicates an important overlap between the domains. The volume of the segmented tissues is over-estimated for the bones and skin-with 1.313 and 1.113 ratios of the estimated over reference volumes, respectively-and under-estimated in the case of the lungs with a 0.762 ratio. The mean point to surface distance is inferior to the voxel size of 400 μm, for the three segmented tissues. These results are very encouraging and let us consider micro-DT as an alternative to micro-CT to deal with geometrical constraints.

  18. A Review of Translational Animal Models for Knee Osteoarthritis

    PubMed Central

    Gregory, Martin H.; Capito, Nicholas; Kuroki, Keiichi; Stoker, Aaron M.; Cook, James L.; Sherman, Seth L.

    2012-01-01

    Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are important considerations for choosing an appropriate animal model. Smaller animals are useful because of their ease of use and cost, while larger animals are advantageous because of their anatomical similarity to humans. This evidence-based review will compare and contrast several different animal models for knee osteoarthritis. Our goal is to inform the clinician about current research models, in order to facilitate the transfer of knowledge from the “bench” to the “bedside.” PMID:23326663

  19. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    NASA Astrophysics Data System (ADS)

    Halloran, Siobhan; Ristenpart, William

    2013-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in pathogen transmission between the animals, to date the infectious disease community has paid little attention to the effect of airspeed or turbulent intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of an axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We show that for fan-generated turbulence the plume width is invariant with the mean airspeed and, close to the point source, increases linearly with downstream position. Importantly, the turbulent dispersivity is insensitive to the presence of meshes placed downstream from the point source, indicating that the fan length scale dictates the turbulent intensity and corresponding dispersivity.

  20. Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations.

    PubMed

    Stei, Marta M; Loeffler, Karin U; Holz, Frank G; Herwig, Martina C

    2016-01-01

    Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field.

  1. Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

    PubMed Central

    Stei, Marta M.; Loeffler, Karin U.; Holz, Frank G.; Herwig, Martina C.

    2016-01-01

    Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field. PMID:27366747

  2. Reproducibility Issues: Avoiding Pitfalls in Animal Inflammation Models.

    PubMed

    Laman, Jon D; Kooistra, Susanne M; Clausen, Björn E

    2017-01-01

    In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives, that is, replacing, reducing, and refining animal experiments-the three R's of Russel and Burch (1959)-understanding the complex interactions of the cells of the immune system, the nervous system and the affected tissue/organ during inflammation critically relies on in vivo models. Consequently, scientific advancement and ultimately novel therapeutic interventions depend on improving the reproducibility of animal inflammation models. As a prelude to the remaining hands-on protocols described in this volume, here, we summarize potential pitfalls of preclinical animal research and provide resources and background reading on how to avoid them.

  3. Pain assessment in animal models of osteoarthritis.

    PubMed

    Piel, Margaret J; Kroin, Jeffrey S; van Wijnen, Andre J; Kc, Ranjan; Im, Hee-Jeong

    2014-03-10

    Assessment of pain in animal models of osteoarthritis is integral to interpretation of a model's utility in representing the clinical condition, and enabling accurate translational medicine. Here we describe behavioral pain assessments available for small and large experimental osteoarthritic pain animal models.

  4. Animal Models of Psychosis: Current State and Future Directions

    PubMed Central

    Forrest, Alexandra D.; Coto, Carlos A.; Siegel, Steven J.

    2014-01-01

    Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability. PMID:25215267

  5. Animal models of respiratory syncytial virus infection.

    PubMed

    Taylor, Geraldine

    2017-01-11

    , interpretation of findings from many rodent and NHP models of vaccine-enhanced hRSV disease has been confounded by sensitisation to non-viral antigens present in the vaccine and challenge virus. Studies of non-human pneumoviruses in their native hosts are more likely to reflect the pathogenesis of natural hRSV infection, and experimental infection of calves with bRSV and of mice with PVM result in clinical disease and extensive pulmonary pathology. These animal models have not only been of value in studies on mechanisms of immunity to and the pathogenesis of pneumovirus infections but have also been used to evaluate hRSV vaccine concepts. Furthermore, the similarities between the epidemiology of bRSV in calves and hRSV in infants and the high level of genetic and antigenic similarity between bRSV and hRSV, make the calf model of bRSV infection a relevant model for preclinical evaluation of hRSV vaccine candidates which contain proteins that are conserved between hRSV and bRSV.

  6. Exploring the Validity of Valproic Acid Animal Model of Autism

    PubMed Central

    Mabunga, Darine Froy N.; Gonzales, Edson Luck T.; Kim, Ji-woon; Kim, Ki Chan

    2015-01-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD. PMID:26713077

  7. Evaluation of spinal cord injury animal models

    PubMed Central

    Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784

  8. PAIN ASSESSMENT IN ANIMAL MODELS OF OSTEOARTHRITIS

    PubMed Central

    Piel, Margaret J; Kroin, Jeffrey S; van Wijnen, Andre J; Kc, Ranjan; Im, Hee-Jeong

    2014-01-01

    Assessment of pain in animal models of osteoarthritis is integral to interpretation of a model’s utility in representing the clinical condition, and enabling accurate translational medicine. Here we describe behavioral pain assessments available for small and large experimental osteoarthritic pain animal models. PMID:24333346

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

    PubMed

    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.

  10. Animal model and neurobiology of suicide.

    PubMed

    Preti, Antonio

    2011-06-01

    Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk.

  11. Experimental animal models in periodontology: a review.

    PubMed

    Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre

    2010-04-29

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and primates have been used for modeling human periodontal diseases and treatments. However, both the anatomy and physiopathology of animals are different from those of humans, making difficult the evaluation of new therapies. Experimental models have been developed in order to reproduce major periodontal diseases (gingivitis, periodontitis), their pathogenesis and to investigate new surgical techniques. The aim of this review is to define the most pertinent animal models for periodontal research depending on the hypothesis and expected results.

  12. The National Research Initiative Competitive Grants Program in animal reproduction: changes in priorities and scope relevant to United States animal agriculture.

    PubMed

    Mirando, M A

    2007-03-01

    The National Research Initiative (NRI) Competitive Grants Program is the USDA's major competitive grants program and is administered by the Cooperative State Research, Education, and Extension Service. The NRI was authorized by the US Congress in the 1990 Farm Bill at a funding level of $500 million; however, the maximal NRI appropriation was $181.17 million in fiscal year (FY) 2006. Across all programs, the NRI is mandated to use 40% of its funding to support mission-linked research. Since its inception in 1991, the NRI has funded competitive grants in the discipline of animal reproduction. Before 2004, the Animal Reproduction Program funded a broad range of projects encompassing almost every subdiscipline in reproductive biology of farm animals, including aquatic species important to the aquaculture industry and laboratory animals. During FY 2004, the NRI Animal Reproduction Program narrowed the focus of its funding priorities to 5 issue-based topics in an effort to make greater measurable improvements in a few high-impact areas over the next 10 years. Funding priorities were narrowed further in FY 2006 to 3 subdisciplines based, in part, on recommendations that emerged from a stakeholder workshop conducted by Cooperative State Research, Education, and Extension Service in August 2004. In FY 2003, Congress authorized expenditure of up to 20% of the funds appropriated to the NRI to support projects that integrate at least 2 of the 3 functions of research, education, and extension. In FY 2004, the Animal Reproduction Program included a funding priority for integrated projects focused primarily on infertility in dairy cattle. The program funded its first integrated project in FY 2005. During FY 2002, increased emphasis on justification for the use of model systems (e.g., laboratory animals and in vitro systems) was included in the NRI request for applications. In FY 2006, applications proposing to primarily utilize nonagricultural animal models were excluded from

  13. Campylobacter species in animal, food, and environmental sources, and relevant testing programs in Canada.

    PubMed

    Huang, Hongsheng; Brooks, Brian W; Lowman, Ruff; Carrillo, Catherine D

    2015-10-01

    Campylobacter species, particularly thermophilic campylobacters, have emerged as a leading cause of human foodborne gastroenteritis worldwide, with Campylobacter jejuni, Campylobacter coli, and Campylobacter lari responsible for the majority of human infections. Although most cases of campylobacteriosis are self-limiting, campylobacteriosis represents a significant public health burden. Human illness caused by infection with campylobacters has been reported across Canada since the early 1970s. Many studies have shown that dietary sources, including food, particularly raw poultry and other meat products, raw milk, and contaminated water, have contributed to outbreaks of campylobacteriosis in Canada. Campylobacter spp. have also been detected in a wide range of animal and environmental sources, including water, in Canada. The purpose of this article is to review (i) the prevalence of Campylobacter spp. in animals, food, and the environment, and (ii) the relevant testing programs in Canada with a focus on the potential links between campylobacters and human health in Canada.

  14. Animal models for the study of tendinopathy.

    PubMed

    Warden, S J

    2007-04-01

    Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.

  15. Animal models for the study of tendinopathy

    PubMed Central

    Warden, S J

    2007-01-01

    Tendinopathy is a common and significant clinical problem characterised by activity‐related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated. PMID:17127722

  16. A systematic review of animal models for Staphylococcus aureus osteomyelitis

    PubMed Central

    Reizner, W.; Hunter, J.G.; O’Malley, N.T.; Southgate, R.D.; Schwarz, E.M.; Kates, S.L.

    2015-01-01

    Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed & Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorized by animal species and are further classified by the setting of the infection. Study methods are summarized and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model’s strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting. PMID:24668594

  17. Animal Models in Studying Cerebral Arteriovenous Malformation.

    PubMed

    Xu, Ming; Xu, Hongzhi; Qin, Zhiyong

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term "arteriovenous malformation," limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected.

  18. Animal Models in Studying Cerebral Arteriovenous Malformation

    PubMed Central

    Xu, Ming; Xu, Hongzhi; Qin, Zhiyong

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected. PMID:26649296

  19. Overview of Animal Models of Obesity

    PubMed Central

    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

  20. Animal models of external traumatic wound infections

    PubMed Central

    Dai, Tianhong; Kharkwal, Gitika B; Tanaka, Masamitsu; Huang, Ying-Ying; Bil de Arce, Vida J

    2011-01-01

    Background: Despite advances in traumatic wound care and management, infections remain a leading cause of mortality, morbidity and economic disruption in millions of wound patients around the world. Animal models have become standard tools for studying a wide array of external traumatic wound infections and testing new antimicrobial strategies. Results: Animal models of external traumatic wound infections reported by different investigators vary in animal species used, microorganism strains, the number of microorganisms applied, the size of the wounds and for burn infections, the length of time the heated object or liquid is in contact with the skin. Methods: This review covers experimental infections in animal models of surgical wounds, skin abrasions, burns, lacerations, excisional wounds and open fractures. Conclusions: As antibiotic resistance continues to increase, more new antimicrobial approaches are urgently needed. These should be tested using standard protocols for infections in external traumatic wounds in animal models. PMID:21701256

  1. Engineering large animal models of human disease.

    PubMed

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  2. Animal models for testing anti-prion drugs.

    PubMed

    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.

  3. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Animal models for simulating weightlessness

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E.; Wronski, T. J.

    1982-01-01

    NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.

  5. Animal models for simulating weightlessness

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E.; Wronski, T. J.

    1982-01-01

    NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.

  6. Animal Models for Cartilage Regeneration and Repair

    PubMed Central

    Szczodry, Michal; Bruno, Stephen

    2010-01-01

    Articular cartilage injury and degeneration are leading causes of disability. Animal studies are critically important to developing effective treatments for cartilage injuries. This review focuses on the use of animal models for the study of the repair and regeneration of focal cartilage defects. Animals commonly used in cartilage repair studies include murine, lapine, canine, caprine, porcine, and equine models. There are advantages and disadvantages to each model. Small animal rodent and lapine models are cost effective, easy to house, and useful for pilot and proof-of-concept studies. The availability of transgenic and knockout mice provide opportunities for mechanistic in vivo study. Athymic mice and rats are additionally useful for evaluating the cartilage repair potential of human cells and tissues. Their small joint size, thin cartilage, and greater potential for intrinsic healing than humans, however, limit the translational value of small animal models. Large animal models with thicker articular cartilage permit study of both partial thickness and full thickness chondral repair, as well as osteochondral repair. Joint size and cartilage thickness for canine, caprine, and mini-pig models remain significantly smaller than that of humans. The repair and regeneration of chondral and osteochondral defects of size and volume comparable to that of clinically significant human lesions can be reliably studied primarily in equine models. While larger animals may more closely approximate the human clinical situation, they carry greater logistical, financial, and ethical considerations. A multifactorial analysis of each animal model should be carried out when planning in vivo studies. Ultimately, the scientific goals of the study will be critical in determining the appropriate animal model. PMID:19831641

  7. Evaluating animal models: some taxonomic worries.

    PubMed

    Degeling, Chris; Johnson, Jane

    2013-04-01

    The seminal 1993 article by LaFollette and Shanks "Animal Models in Biomedical Research: Some Epistemological Worries" introduced an influential taxonomy into the debate about the value of animal experimentation. The distinction they made between hypothetical and causal analog models served to highlight a concern regarding extrapolating results obtained in animal models to human subjects, which endures today. Although their taxonomy has made a significant contribution to the field, we maintain that it is flawed, and instead, we offer a new practice-oriented taxonomy of animal models as a means to allow philosophers, modelers, and other interested parties to discuss the epistemic merits and shortcomings, purpose, and predictive capacities of specific modeling practices.

  8. Animal Models for Progressive Multifocal Leukoencephalopathy.

    PubMed

    White, Martyn K; Gordon, Jennifer; Berger, Joseph R; Khalili, Kamel

    2015-12-01

    Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the CNS caused by the human polyomavirus JC (JCV). JCV replication occurs only in human cells and investigation of PML has been severely hampered by the lack of an animal model. The common feature of PML is impairment of the immune system. The key to understanding PML is working out the complex mechanisms that underlie viral entry and replication within the CNS and the immunosurveillance that suppresses the virus or allows it to reactivate. Early models involved the simple inoculation of JCV into animals such as monkeys, hamsters, and mice. More recently, mouse models transgenic for the gene encoding the JCV early protein, T-antigen, a protein thought to be involved in the disruption of myelin seen in PML, have been employed. These animal models resulted in tumorigenesis rather than demyelination. Another approach is to use animal polyomaviruses that are closely related to JCV but able to replicate in the animal such as mouse polyomavirus and SV40. More recently, novel models have been developed that involve the engraftment of human cells into the animal. Here, we review progress that has been made to establish an animal model for PML, the advances and limitations of different models and weigh future prospects. © 2015 Wiley Periodicals, Inc.

  9. Intestinal Microbiota in Animal Models of Inflammatory Diseases.

    PubMed

    Hörmannsperger, G; Schaubeck, M; Haller, D

    2015-01-01

    The intestinal microbiota has long been known to play an important role in the maintenance of health. In addition, alterations of the intestinal microbiota have recently been associated with a range of immune-mediated and metabolic disorders. Characterizing the composition and functionality of the intestinal microbiota, unravelling relevant microbe-host interactions, and identifying disease-relevant microbes are therefore currently of major interest in scientific and medical communities. Experimental animal models for the respective diseases of interest are pivotal in order to address functional questions on microbe-host interaction and to clarify the clinical relevance of microbiome alterations associated with disease initiation and development. This review presents an overview of the outcomes of highly sophisticated experimental studies on microbe-host interaction in animal models of inflammatory diseases, with a focus on inflammatory bowel disease (IBD). We will address the advantages and drawbacks of analyzing microbe-host interaction in complex colonized animal models compared with gnotobiotic animal models using monoassociation, simplified microbial consortia (SMC), or microbial humanization.

  10. Animal models of suicide-trait-related behaviors.

    PubMed

    Malkesman, Oz; Pine, Daniel S; Tragon, Tyson; Austin, Daniel R; Henter, Ioline D; Chen, Guang; Manji, Husseini K

    2009-04-01

    Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.

  11. Animal models of organic heart valve disease.

    PubMed

    Roosens, Bram; Bala, Gezim; Droogmans, Steven; Van Camp, Guy; Breyne, Joke; Cosyns, Bernard

    2013-05-25

    Heart valve disease is a frequently encountered pathology, related to high morbidity and mortality rates in industrialized and developing countries. Animal models are interesting to investigate the causality, but also underlying mechanisms and potential treatments of human valvular diseases. Recently, animal models of heart valve disease have been developed, which allow to investigate the pathophysiology, and to follow the progression and the potential regression of disease with therapeutics over time. The present review provides an overview of animal models of primary, organic heart valve disease: myxoid age-related, infectious, drug-induced, degenerative calcified, and mechanically induced valvular heart disease. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Comparative juvenile safety testing of new therapeutic candidates: relevance of laboratory animal data to children.

    PubMed

    Anderson, Tim; Khan, Nasir K; Tassinari, Melissa S; Hurtt, Mark E

    2009-01-01

    Differences in drug response in patients of various ages including children and the elderly are common, often leading to challenges in optimizing dosages and duration of use. For example, developmental changes in renal function can dramatically alter the plasma clearance of compounds with extensive renal elimination and thus can enhance renal and systemic toxicity of these drugs. Preclinical and clinical research of new therapeutics is initially focused on adults, and provides little relevant information for children especially those who are still going through skeletal and organ development. The organ systems in the pediatric population that can be most susceptible are lungs, brain, kidneys, immune, skeletal, and reproductive systems. Considering that significant differences can exist between adult and juvenile populations that may affect drug safety, major regulatory agencies around the world are encouraging and sometimes requiring companies to generate preclinical juvenile animal data to predict for potential drug toxicity in children. However, data generated from such studies are useful only if obtained using the most appropriate species at the most relevant age considering comparability of specific organ system development in question. Other factors in the design of juvenile safety studies should include the indication, existing toxicological data and likely route of human exposure. This report will discuss these factors with a focus on reviewing species-specific developmental schedules for specific target organs and relevance of preclinical data in the design and conduct of clinical pediatric studies. Specific examples will be used to discuss the relationship of preclinical juvenile toxicity observations to risk assessment in humans.

  13. Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

    PubMed

    Rollin, Michael D H; Rollin, Bernard E

    2014-04-01

    Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

  14. Animal models: an important tool in mycology.

    PubMed

    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.

  15. Proteomics in farm animals models of human diseases.

    PubMed

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques.

  16. Animal Models of Tuberculosis: Zebrafish

    PubMed Central

    van Leeuwen, Lisanne M.; van der Sar, Astrid M.; Bitter, Wilbert

    2015-01-01

    Over the past decade the zebrafish (Danio rerio) has become an attractive new vertebrate model organism for studying mycobacterial pathogenesis. The combination of medium-throughput screening and real-time in vivo visualization has allowed new ways to dissect host pathogenic interaction in a vertebrate host. Furthermore, genetic screens on the host and bacterial sides have elucidated new mechanisms involved in the initiation of granuloma formation and the importance of a balanced immune response for control of mycobacterial pathogens. This article will highlight the unique features of the zebrafish–Mycobacterium marinum infection model and its added value for tuberculosis research. PMID:25414379

  17. Using animal models to develop therapeutics for Tourette Syndrome.

    PubMed

    Swerdlow, Neal R; Sutherland, Ashley N

    2005-12-01

    The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis and will be enhanced through the use of animal models. Particular challenges in the development of TS animal models reflect complex features of this disorder, including its waxing and waning course and its "invisible" sensory and psychic symptoms. Animal models can achieve face, predictive, or construct validity based on their particular features. Predictive validity, of most direct relevance to drug development for TS, is achieved to some degree by a several animal models, although the reliance of most of these models on measures of motor suppression may ultimately limit their utility. Other models achieve construct validity with proposed pathophysiological mechanisms related to the immune and neural circuit etiologies of TS. One model-deficient sensorimotor gating of the startle reflex-is discussed in terms of its present and future applications towards advancing our understanding of the pathophysiology and treatment of TS. In addition to models that will advance the pharmacotherapy of TS, other animal models may enhance the utility of nonpharmacologic TS treatments, ranging from behavior therapy to deep brain stimulation (DBS).

  18. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    EPA Science Inventory

    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.

  19. A Relevant Model for Preparing Aspiring Superintendents

    ERIC Educational Resources Information Center

    Robicheau, Jerry; Haar, Jean

    2008-01-01

    The relevance of administrative preparation programs has been questioned. The questions center around how well programs are preparing school leaders to deal with the myriad of requirements placed in front of them (i.e. demands relate to issues of accountability, changing demographics, aging professionals, demanding publics, and school…

  20. Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis

    PubMed Central

    Fang, Longhou; Liu, Chao; Miller, Yury I.

    2013-01-01

    Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease. PMID:24095954

  1. Animal models of monogenic migraine.

    PubMed

    Chen, Shih-Pin; Tolner, Else A; Eikermann-Haerter, Katharina

    2016-06-01

    Migraine is a highly prevalent and disabling neurological disorder with a strong genetic component. Rare monogenic forms of migraine, or syndromes in which migraine frequently occurs, help scientists to unravel pathogenetic mechanisms of migraine and its comorbidities. Transgenic mouse models for rare monogenic mutations causing familial hemiplegic migraine (FHM), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and familial advanced sleep-phase syndrome (FASPS), have been created. Here, we review the current state of research using these mutant mice. We also discuss how currently available experimental approaches, including epigenetic studies, biomolecular analysis and optogenetic technologies, can be used for characterization of migraine genes to further unravel the functional and molecular pathways involved in migraine.

  2. Animal models of orthopedic implant infection.

    PubMed

    An, Y H; Friedman, R J

    1998-01-01

    Prosthetic infection following total joint replacement can have catastrophic results both physically and psychologically for patients, leading to complete failure of the arthroplasty, possible amputation, prolonged hospitalization, and even death. Although with the use of prophylactic antibiotics and greatly improved operating room techniques the infection rate has decreased markedly during the years, challenges still remain for better preventive and therapeutic measures. In this review the in vivo experimental methods for studies of prosthetic infection are discussed, concentrating on (1) the animal models that have been established and the use of these animal models for studies of pathogenesis of bacteria, behavior of biofilm, effect of biomaterials on prosthetic infection rate, and the effect of infection on biomaterial surfaces, and (2) how to design and conduct an animal model of orthopedic prosthetic infection including animal selection, implant fabrication, bacterial inoculation, surgical technique, and the methods for evaluating the results.

  3. Animal models for SARS and MERS coronaviruses.

    PubMed

    Gretebeck, Lisa M; Subbarao, Kanta

    2015-08-01

    The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV.

  4. Animal models for SARS and MERS coronaviruses

    PubMed Central

    Gretebeck, Lisa M; Subbarao, Kanta

    2015-01-01

    The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV. PMID:26184451

  5. Building models of animals from video.

    PubMed

    Ramanan, Deva; Forsyth, David A; Barnard, Kobus

    2006-08-01

    This paper argues that tracking, object detection, and model building are all similar activities. We describe a fully automatic system that builds 2D articulated models known as pictorial structures from videos of animals. The learned model can be used to detect the animal in the original video--in this sense, the system can be viewed as a generalized tracker (one that is capable of modeling objects while tracking them). The learned model can be matched to a visual library; here, the system can be viewed as a video recognition algorithm. The learned model can also be used to detect the animal in novel images--in this case, the system can be seen as a method for learning models for object recognition. We find that we can significantly improve the pictorial structures by augmenting them with a discriminative texture model learned from a texture library. We develop a novel texture descriptor that outperforms the state-of-the-art for animal textures. We demonstrate the entire system on real video sequences of three different animals. We show that we can automatically track and identify the given animal. We use the learned models to recognize animals from two data sets; images taken by professional photographers from the Corel collection, and assorted images from the Web returned by Google. We demonstrate quite good performance on both data sets. Comparing our results with simple baselines, we show that, for the Google set, we can detect, localize, and recover part articulations from a collection demonstrably hard for object recognition.

  6. Progress With Nonhuman Animal Models of Addiction.

    PubMed

    Crabbe, John C

    2016-09-01

    Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten.

  7. Animal models of Parkinson's disease: a gateway to therapeutics?

    PubMed

    Le, Weidong; Sayana, Pavani; Jankovic, Joseph

    2014-01-01

    Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.

  8. Animal models in motion sickness research

    NASA Technical Reports Server (NTRS)

    Daunton, Nancy G.

    1990-01-01

    Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

  9. Animal models in motion sickness research

    NASA Technical Reports Server (NTRS)

    Daunton, Nancy G.

    1990-01-01

    Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

  10. OVERVIEW: USING MODE OF ACTION AND LIFE STAGE INFORMATION TO EVALUATE THE HUMAN RELEVANCE OF ANIMAL TOXICITY DATA.

    EPA Science Inventory

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...

  11. OVERVIEW: USING MODE OF ACTION AND LIFE STAGE INFORMATION TO EVALUATE THE HUMAN RELEVANCE OF ANIMAL TOXICITY DATA.

    EPA Science Inventory

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...

  12. Implementing Relevance Feedback in the Bayesian Network Retrieval Model.

    ERIC Educational Resources Information Center

    de Campos, Luis M.; Fernandez-Luna, Juan M.; Huete, Juan F.

    2003-01-01

    Discussion of relevance feedback in information retrieval focuses on a proposal for the Bayesian Network Retrieval Model. Bases the proposal on the propagation of partial evidences in the Bayesian network, representing new information obtained from the user's relevance judgments to compute the posterior relevance probabilities of the documents…

  13. Animal models of human response to dioxins.

    PubMed Central

    Grassman, J A; Masten, S A; Walker, N J; Lucier, G W

    1998-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. PMID:9599728

  14. Animal models for rotator cuff repair.

    PubMed

    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.

  15. Animal models of idiosyncratic drug reactions.

    PubMed

    Ng, Winnie; Lobach, Alexandra R M; Zhu, Xu; Chen, Xin; Liu, Feng; Metushi, Imir G; Sharma, Amy; Li, Jinze; Cai, Ping; Ip, Julia; Novalen, Maria; Popovic, Marija; Zhang, Xiaochu; Tanino, Tadatoshi; Nakagawa, Tetsuya; Li, Yan; Uetrecht, Jack

    2012-01-01

    If we could predict and prevent idiosyncratic drug reactions (IDRs) it would have a profound effect on drug development and therapy. Given our present lack of mechanistic understanding, this goal remains elusive. Hypothesis testing requires valid animal models with characteristics similar to the idiosyncratic reactions that occur in patients. Although it has not been conclusively demonstrated, it appears that almost all IDRs are immune-mediated, and a dominant characteristic is a delay between starting the drug and the onset of the adverse reaction. In contrast, most animal models are acute and therefore involve a different mechanism than idiosyncratic reactions. There are, however, a few animal models such as the nevirapine-induced skin rash in rats that have characteristics very similar to the idiosyncratic reaction that occurs in humans and presumably have a very similar mechanism. These models have allowed testing hypotheses that would be impossible to test in any other way. In addition there are models in which there is a delayed onset of mild hepatic injury that resolves despite continued treatment similar to the "adaptation" reactions that are more common than severe idiosyncratic hepatotoxicity in humans. This probably represents the development of immune tolerance. However, most attempts to develop animal models by stimulating the immune system have been failures. A specific combination of MHC and T cell receptor may be required, but it is likely more complex. Animal studies that determine the requirements for an immune response would provide vital clues about risk factors for IDRs in patients.

  16. Large Animal Models of Huntington's Disease.

    PubMed

    Li, Xiao-Jiang; Li, Shihua

    2015-01-01

    Huntington's disease is caused by the expansion of a polyglutamine repeat (>37 glutamines) in the disease protein huntingtin, which results in preferential neuronal loss in distinct brain regions. Mutant huntingtin causes late-onset neurological symptoms in patients in middle life, though the expression of mutant huntingtin is ubiquitous from early life. Thus, it is important to understand why mutant huntingtin selectively causes neuronal loss in an age-dependent manner. Transgenic animal models have been essential tools for uncovering the pathogenesis and therapeutic targets of neurodegenerative diseases. Genetic mouse models have been investigated extensively and have revealed the common pathological hallmark of age-dependent formation of aggregates or inclusions consisting of misfolded proteins. However, most genetic mouse models lack striking neurodegeneration that has been found in patient brains. Since there are considerable species differences between small and large animals, large animal models of Huntington's disease may allow one to identify the pathological features that are more similar to those in patients and also help uncover more effective therapeutic targets. This chapter will focus on the important findings from large animal models of Huntington's disease and discusses the use of large animal models to investigate the pathogenesis of Huntington's disease and develop new therapeutic strategies.

  17. Importance of animal models in schizophrenia research.

    PubMed

    van den Buuse, M; Garner, B; Gogos, A; Kusljic, S

    2005-07-01

    This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.

  18. Sex differences in animal models of psychiatric disorders

    PubMed Central

    Kokras, N; Dalla, C

    2014-01-01

    Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive–compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24697577

  19. Current status: Animal models of nausea

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.

    1991-01-01

    The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

  20. Animal models of hepatitis A and E.

    PubMed

    Purcell, R H; Emerson, S U

    2001-01-01

    Several useful animal models for both hepatitis A and E have been identified, characterized, and refined. At present, all of the best models utilize nonhuman primates: chimpanzees, tamarin species, and owl monkeys for hepatitis A; and macaque species, chimpanzees, and owl monkeys for hepatitis E. Pigs may prove useful for some studies of hepatitis E, and it is hoped that serological evidence of widespread infection of rats with an HEV-like agent may lead to the development of an animal model based on laboratory rats. As has been the case for each of the hepatitis viruses as they have been discovered, the development of useful and reproducible animal model systems has been critical for moving the field forward as expeditiously as possible.

  1. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    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. PMID:26784179

  2. Optogenetics in animal model of alcohol addiction

    NASA Astrophysics Data System (ADS)

    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.

  3. Animal Models of Maternal Immune Activation in Depression Research

    PubMed Central

    Ronovsky, Marianne; Berger, Stefanie; Molz, Barbara; Berger, Angelika; Pollak, Daniela D.

    2016-01-01

    Abstract: Background Depression and schizophrenia are debilitating mental illnesses with significant socio-economic impact. The high degree of comorbidity between the two disorders, and shared symptoms and risk factors, suggest partly common pathogenic mechanisms. Supported by human and animal studies, maternal immune activation (MIA) has been intimately associated with the development of schizophrenia. However, the link between MIA and depression has remained less clear, in part due to the lack of appropriate animal models. Objective Here we aim to summarize findings obtained from studies using MIA animal models and discuss their relevance for preclinical depression research. Methods Results on molecular, cellular and behavioral phenotypes in MIA animal models were collected by literature search (PubMed) and evaluated for their significance for depression. Results Several reports on offspring depression-related behavioral alterations indicate an involvement of MIA in the development of depression later in life. Depression-related behavioral phenotypes were frequently paralleled by neurogenic and neurotrophic deficits and modulated by several genetic and environmental factors. Conclusion Literature evidence analyzed in this review supports a relevance of MIA as animal model for a specific early life adversity, which may prime an individual for the development of distinct psychopathologies later life. MIA animal models may present a unique tool for the identification of additional exogenous and endogenous factors, which are required for the manifestation of a specific neuropsychiatric disorder, such as depression, later in life. Hereby, novel insights into the molecular mechanisms involved in the pathophysiology of depression may be obtained, supporting the identification of alternative therapeutic strategies. PMID:26666733

  4. Role of Animal Models in Coronary Stenting.

    PubMed

    Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

    2016-02-01

    Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

  5. Animal models for lysosomal storage disorders.

    PubMed

    Pastores, G M; Torres, P A; Zeng, B-J

    2013-07-01

    The lysosomal storage disorders (LSD) represent a heterogeneous group of inherited diseases characterized by the accumulation of non-metabolized macromolecules (by-products of cellular turnover) in different tissues and organs. LSDs primarily develop as a consequence of a deficiency in a lysosomal hydrolase or its co-factor. The majority of these enzymes are glycosidases and sulfatases, which in normal conditions participate in degradation of glycoconjugates: glycoproteins, glycosaminoproteoglycans, and glycolipids. Significant insights have been gained from studies of animal models, both in understanding mechanisms of disease and in establishing proof of therapeutic concept. These studies have led to the introduction of therapy for certain LSD subtypes, primarily by enzyme replacement or substrate reduction therapy. Animal models have been useful in elucidating molecular changes, particularly prior to onset of symptoms. On the other hand, it should be noted certain animal (mouse) models may have the underlying biochemical defect, but not show the course of disease observed in human patients. There is interest in examining therapeutic options in the larger spontaneous animal models that may more closely mimic the brain size and pathology of humans. This review will highlight lessons learned from studies of animal models of disease, drawing primarily from publications in 2011-2012.

  6. Animal models of gastrointestinal inflammation and cancer.

    PubMed

    Lu, L; Chan, Ruby L Y; Luo, X M; Wu, William K K; Shin, Vivian Y; Cho, C H

    2014-07-11

    Inflammation and cancer are the two major disorders in the gastrointestinal tract. They are causally related in their pathogenesis. It is important to study animal models' causal relationship and, in particular, to discover new therapeutic agents for such diseases. There are several criteria for these models in order to make them useful in better understanding the etiology and treatment of the said diseases in humans. In this regard, animal models should be similar as possible to human diseases and also be easy to produce and reproducible and also economic to allow a continuous replication in different laboratories. In this review, we summarize the various animal models for inflammatory and cancerous disorders in the upper and lower gastrointestinal tract. Experimental approaches are as simple as by giving a single oral dose of alcohol or other noxious agents or by injections of multiple dosages of ulcer inducing agents or by parenteral administration or in drinking water of carcinogens or by modifying the genetic makeups of animals to produce relatively long-term pathological changes in particular organs. With these methods they could induce consistent inflammatory responses or tumorigenesis in the gastrointestinal mucosa. These animal models are widely used in laboratories in understanding the pathogenesis as well as the mechanisms of action for therapeutic agents in the treatment of gastrointestinal inflammation and cancer.

  7. Animal Models for HIV Cure Research.

    PubMed

    Policicchio, Benjamin B; Pandrea, Ivona; Apetrei, Cristian

    2016-01-01

    The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.

  8. Pharmacokinetic modeling in aquatic animals. 1. Models and concepts

    USGS Publications Warehouse

    Barron, M.G.; Stehly, Guy R.; Hayton, W.L.

    1990-01-01

    While clinical and toxicological applications of pharmacokinetics have continued to evolve both conceptually and experimentally, pharmacokinetics modeling in aquatic animals has not progressed accordingly. In this paper we present methods and concepts of pharmacokinetic modeling in aquatic animals using multicompartmental, clearance-based, non-compartmental and physiologically-based pharmacokinetic models. These models should be considered as alternatives to traditional approaches, which assume that the animal acts as a single homogeneous compartment based on apparent monoexponential elimination.

  9. Animal models of transcranial direct current stimulation: Methods and mechanisms.

    PubMed

    Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

    2016-11-01

    The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the

  10. Large animal models for stem cell therapy.

    PubMed

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  11. Large animal models for stem cell therapy

    PubMed Central

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  12. Engel's biopsychosocial model is still relevant today.

    PubMed

    Adler, Rolf H

    2009-12-01

    In 1977, Engel published the seminal paper, "The Need for a New Medical Model: A Challenge for Biomedicine" [Science 196 (1977) 129-136]. He featured a biopsychosocial (BPS) model based on systems theory and on the hierarchical organization of organisms. In this essay, the model is extended by the introduction of semiotics and constructivism. Semiotics provides the language which allows to describe the relationships between the individual and his environment. Constructivism explains how an organism perceives his environment. The impact of the BPS model on research, medical education, and application in the practice of medicine is discussed.

  13. Food allergy animal models: an overview.

    PubMed

    Helm, Ricki M

    2002-05-01

    Specific food allergy is characterized by sensitization to innocuous food proteins with production of allergen-specific IgE that binds to receptors on basophils and mast cells. Upon recurrent exposure to the same allergen, an allergic response is induced by mediator release following cross-linking of cell-bound allergen-specific IgE. The determination of what makes an innocuous food protein an allergen in predisposed individuals is unknown; however, mechanistic and protein allergen predictive models are being actively investigated in a number of animal models. Currently, there is no animal model that will actively profile known food allergens, predict the allergic potential of novel food proteins, or demonstrate clinically the human food allergic sensitization/allergic response. Animal models under investigation include mice, rats, the guinea pig, atopic dog, and neonatal swine. These models are being assessed for production of IgE, clinical responses to re-exposure, and a ranking of food allergens (based on potency) including a nonfood allergen protein source. A selection of animal models actively being investigated that will contribute to our understanding of what makes a protein an allergen and future predictive models for assessing the allergenicity of novel proteins is presented in this review.

  14. Review of Nonprimate, Large Animal Models for Osteoporosis Research

    PubMed Central

    Reinwald, Susan; Burr, David

    2008-01-01

    Large animal models are required for preclinical prevention and intervention studies related to osteoporosis research. The challenging aspect of this requirement is that no single animal model exactly mimics the progression of this human-specific chronic condition. There are pros and cons associated with the skeletal, hormonal, and metabolic conditions of each species that influence their relevance and applicability to human physiology. Of all larger mammalian species, nonhuman primates (NHPs) are preeminent in terms of replicating important aspects of human physiology. However, NHPs are very expensive, putting them out of reach of the vast majority of researchers. Practical, cost-effective alternatives to NHPs are sought after among ungulate (porcine, caprine, and ovine) and canine species that are the focus of this review. The overriding caveat to using large lower-order species is to take the time in advance to understand and appreciate the limitations and strengths of each animal model. Under these circumstances, experiments can be strategically designed to optimize the potential of an animal to develop the cardinal features of postmenopausal bone loss and/or yield information of relevance to treatment. PMID:18505374

  15. Alternative Animal and Non-Animal Models for Drug Discovery and Development: Bonus or Burden?

    PubMed

    Freires, Irlan Almeida; Sardi, Janaina de Cássia Orlandi; de Castro, Ricardo Dias; Rosalen, Pedro Luiz

    2017-04-01

    Mammalian models have served as a basis for R&D over the past decades. Nevertheless, these models are expensive, laborious, may yield results that cannot always be translated into the human in vivo situation and, more recently, have reverberated great social and ethical dilemmas. Hence, the prospect of changes in the global scientific scenario and the Three Rs principle (Reduction, Replacement and Refinement) have encouraged the development of alternative methods to the use of mammals. Despite the efforts, suitable alternative tests are not available in all areas of biomedical research, as regulatory acceptance requires time, prior validation and robust financial and scientific investment. In this perspective, we aim to shed light on the concepts, challenges and perspectives for implementation of innovative alternative animal and non-animal methods in scientific research. The applicability and meaningfulness of invertebrate animal models, in silico analysis and reverse pharmacology are discussed, among other aspects of relevance in today's scenario. Overall, the use of alternative models, including Artemia salina (brine shrimp), Caenorhabditis elegans (roundworm), Danio rerio (zebra fish), Drosophila melanogaster (fruit fly), Galleria mellonella (greater waxmoth) and in silico modelling, increased 909% from 1990 to 2015, as compared to 154% of conventional mammals in the same period. Thus, technological and scientific advancements in the fields of toxicology and drug development seem to have diminished the need for mammalian models. Today, however, mammals still remain critically indispensable to provide - in most cases -reliable data subsidizing and validating translation into the clinical setting.

  16. Standardization of A Physiologic Hypoparathyroidism Animal Model

    PubMed Central

    Jung, Soo Yeon; Kim, Ha Yeong; Park, Hae Sang; Yin, Xiang Yun; Chung, Sung Min; Kim, Han Su

    2016-01-01

    Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX—FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies. PMID:27695051

  17. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

  18. Measuring reinforcement learning and motivation constructs in experimental animals: relevance to the negative symptoms of schizophrenia

    PubMed Central

    Markou, Athina; Salamone, John D.; Bussey, Timothy; Mar, Adam; Brunner, Daniela; Gilmour, Gary; Balsam, Peter

    2013-01-01

    The present review article summarizes and expands upon the discussions that were initiated during a meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS; http://cntrics.ucdavis.edu). A major goal of the CNTRICS meeting was to identify experimental procedures and measures that can be used in laboratory animals to assess psychological constructs that are related to the psychopathology of schizophrenia. The issues discussed in this review reflect the deliberations of the Motivation Working Group of the CNTRICS meeting, which included most of the authors of this article as well as additional participants. After receiving task nominations from the general research community, this working group was asked to identify experimental procedures in laboratory animals that can assess aspects of reinforcement learning and motivation that may be relevant for research on the negative symptoms of schizophrenia, as well as other disorders characterized by deficits in reinforcement learning and motivation. The tasks described here that assess reinforcement learning are the Autoshaping Task, Probabilistic Reward Learning Tasks, and the Response Bias Probabilistic Reward Task. The tasks described here that assess motivation are Outcome Devaluation and Contingency Degradation Tasks and Effort-Based Tasks. In addition to describing such methods and procedures, the present article provides a working vocabulary for research and theory in this field, as well as an industry perspective about how such tasks may be used in drug discovery. It is hoped that this review can aid investigators who are conducting research in this complex area, promote translational studies by highlighting shared research goals and fostering a common vocabulary across basic and clinical fields, and facilitate the development of medications for the treatment of symptoms mediated by reinforcement learning and motivational deficits. PMID:23994273

  19. Measuring reinforcement learning and motivation constructs in experimental animals: relevance to the negative symptoms of schizophrenia.

    PubMed

    Markou, Athina; Salamone, John D; Bussey, Timothy J; Mar, Adam C; Brunner, Daniela; Gilmour, Gary; Balsam, Peter

    2013-11-01

    The present review article summarizes and expands upon the discussions that were initiated during a meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS; http://cntrics.ucdavis.edu) meeting. A major goal of the CNTRICS meeting was to identify experimental procedures and measures that can be used in laboratory animals to assess psychological constructs that are related to the psychopathology of schizophrenia. The issues discussed in this review reflect the deliberations of the Motivation Working Group of the CNTRICS meeting, which included most of the authors of this article as well as additional participants. After receiving task nominations from the general research community, this working group was asked to identify experimental procedures in laboratory animals that can assess aspects of reinforcement learning and motivation that may be relevant for research on the negative symptoms of schizophrenia, as well as other disorders characterized by deficits in reinforcement learning and motivation. The tasks described here that assess reinforcement learning are the Autoshaping Task, Probabilistic Reward Learning Tasks, and the Response Bias Probabilistic Reward Task. The tasks described here that assess motivation are Outcome Devaluation and Contingency Degradation Tasks and Effort-Based Tasks. In addition to describing such methods and procedures, the present article provides a working vocabulary for research and theory in this field, as well as an industry perspective about how such tasks may be used in drug discovery. It is hoped that this review can aid investigators who are conducting research in this complex area, promote translational studies by highlighting shared research goals and fostering a common vocabulary across basic and clinical fields, and facilitate the development of medications for the treatment of symptoms mediated by reinforcement learning and motivational deficits.

  20. Hierarchical models of animal abundance and occurrence

    USGS Publications Warehouse

    Royle, J. Andrew; Dorazio, R.M.

    2006-01-01

    Much of animal ecology is devoted to studies of abundance and occurrence of species, based on surveys of spatially referenced sample units. These surveys frequently yield sparse counts that are contaminated by imperfect detection, making direct inference about abundance or occurrence based on observational data infeasible. This article describes a flexible hierarchical modeling framework for estimation and inference about animal abundance and occurrence from survey data that are subject to imperfect detection. Within this framework, we specify models of abundance and detectability of animals at the level of the local populations defined by the sample units. Information at the level of the local population is aggregated by specifying models that describe variation in abundance and detection among sites. We describe likelihood-based and Bayesian methods for estimation and inference under the resulting hierarchical model. We provide two examples of the application of hierarchical models to animal survey data, the first based on removal counts of stream fish and the second based on avian quadrat counts. For both examples, we provide a Bayesian analysis of the models using the software WinBUGS.

  1. Pathophysiology and animal modeling of underactive bladder

    PubMed Central

    Tyagi, Pradeep; Smith, Phillip P.; Kuchel, George A.; de Groat, William C.; Birder, Lori A.; Chermansky, Christopher J.; Adam, Rosalyn M.; Tse, Vincent; Chancellor, Michael B.; Yoshimura, Naoki

    2015-01-01

    While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB. PMID:25238890

  2. Animal models of mucositis: implications for therapy.

    PubMed

    Bowen, Joanne M; Gibson, Rachel J; Keefe, Dorothy M K

    2011-01-01

    Alimentary mucositis is a major acute complication in the clinical setting, occurring in a large percentage of patients undergoing cytotoxic therapy. One of the major problems with alimentary mucositis is that the underlying mechanisms behind its development are not entirely understood, which makes it extremely difficult to develop effective interventions. Animal models provide a critical source of knowledge when sampling from patients is unavailable or interventions are yet to be fully tested. This review focuses on the animal models used to increase our understanding of the mechanisms of mucositis and translate new antimucotoxic agents into clinical trials.

  3. Pathophysiology and animal modeling of underactive bladder.

    PubMed

    Tyagi, Pradeep; Smith, Phillip P; Kuchel, George A; de Groat, William C; Birder, Lori A; Chermansky, Christopher J; Adam, Rosalyn M; Tse, Vincent; Chancellor, Michael B; Yoshimura, Naoki

    2014-09-01

    While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.

  4. Laboratory animal models for esophageal cancer

    PubMed Central

    Nair, Dhanya Venugopalan; Reddy, A. Gopala

    2016-01-01

    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. PMID:27956773

  5. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance

    PubMed Central

    Wang, Xin; Lu, Gang; Picinich, Sonia C.

    2010-01-01

    Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable evidence that tea polyphenols, in particular (−)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion, angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention. PMID:19472429

  6. Animal models of focal brain ischemia

    PubMed Central

    2009-01-01

    Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. PMID:20150985

  7. Diabetic cardiac autonomic neuropathy: insights from animal models.

    PubMed

    Stables, Catherine L; Glasser, Rebecca L; Feldman, Eva L

    2013-10-01

    Cardiac autonomic neuropathy (CAN) is a relatively common and often devastating complication of diabetes. The major clinical signs are tachycardia, exercise intolerance, and orthostatic hypotension, but the most severe aspects of this complication are high rates of cardiac events and mortality. One of the earliest manifestations of CAN is reduced heart rate variability, and detection of this, along with abnormal results in postural blood pressure testing and/or the Valsalva maneuver, are central to diagnosis of the disease. The treatment options for CAN, beyond glycemic control, are extremely limited and lack evidence of efficacy. The underlying molecular mechanisms are also poorly understood. Thus, CAN is associated with a poor prognosis and there is a compelling need for research to understand, prevent, and reverse CAN. In this review of the literature we examine the use and usefulness of animal models of CAN in diabetes. Compared to other diabetic complications, the number of animal studies of CAN is very low. The published studies range across a variety of species, methods of inducing diabetes, and timescales examined, leading to high variability in study outcomes. The lack of well-characterized animal models makes it difficult to judge the relevance of these models to the human disease. One major advantage of animal studies is the ability to probe underlying molecular mechanisms, and the limited numbers of mechanistic studies conducted to date are outlined. Thus, while animal models of CAN in diabetes are crucial to better understanding and development of therapies, they are currently under-used.

  8. Review of Soluble Biomarkers of Osteoarthritis: Lessons From Animal Models.

    PubMed

    Legrand, Catherine B; Lambert, Cécile J; Comblain, Fanny V; Sanchez, Christelle; Henrotin, Yves E

    2017-07-01

    Objective Osteoarthritis (OA) is one of the leading causes of disability within the adult population. Currently, its diagnosis is mainly based on clinical examination and standard radiography. To date, there is no way to detect the disease at a molecular level, before the appearance of structural changes and symptoms. So an attractive alternative for monitoring OA is the measurement of biochemical markers in blood, urine, or synovial fluid, which could reflect metabolic changes in joint tissue and therefore disease onset and progression. Animal models are relevant to investigate the early stage of OA and metabolic changes occurring in joint tissues. The goal of this narrative review is to summarize the scientific data available in the literature on soluble biomarkers in animal models of OA. Design A literature search was conducted using the PubMed/Medline and Scopus databases between February 1995 and December 2015. All original articles, systematic and narrative reviews published in French or in English were considered. Results We summarized the data of 69 studies and proposed a classification scheme for OA biomarkers in animal studies, largely inspired by the BIPEDS classification. Conclusions Studies about biomarkers and animal models indicate that some markers could be valuable to monitor OA progression and assess therapeutic response in some animal models.

  9. Lessons Learned from Animal Models of Inherited Bleeding Disorders

    PubMed Central

    Nichols, Timothy C.

    2014-01-01

    Advances in treatment of hemophilia and von Willebrand disease (VWD) depend heavily on the availability of well-characterized animal models. These animals faithfully recapitulate the severe bleeding phenotype that occurs in humans with these inherited bleeding disorders. Research in these animal models represents important early and intermediate steps of translational research aimed at addressing current limitations in treatment such as the development of inhibitory antibodies to coagulation factors VIII and IX (FVIII, FIX) or von Willebrand factor (VWF), the life-long need for frequent venous access, the expense of therapy, and the ongoing need for improved ex vivo coagulation assays and in vivo methods for assessing hemostasis. The primary strengths of research that utilizes these highly relevant animal models include the development of better and safer treatments for hemophilia and VWD. Careful consideration of the strengths and limitations of the specific models is essential for optimizing chances for successful translation of advances to clinical medicine that benefits humans and animals. PMID:26052366

  10. [Laboratory animal infection in modeling intestinal schistosomiasis].

    PubMed

    Zelia, O P

    1984-01-01

    A comparative efficiency of different regimes for infecting laboratory animals has been determined in order to find out optimal conditions under which an experimental model of intestinal schistosomiasis (infection with Schistosoma mansoni) can be maintained. When evaluating the results of laboratory definitive hosts infection we took into account the character of Schistosoma distribution in animals, which with high probability rate was modelled by means of negative binomial distribution. The main parameters of this distribution were used for determination of effective doses and methods of animals infection alongside with generally accepted indices of infection rate and intensiveness. Analysis of the data obtained has shown that the infection of 150 cercarians per mouse and 200 cercarians per golden and striped hairy-footed hamster by their subcutaneous administration creates optimal density of parasites in the host. Results of investigations have shown that striped hairy-footed hamsters can be used as definitive hosts of Schistosoma.

  11. Are animal models predictive for humans?

    PubMed Central

    2009-01-01

    It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. PMID:19146696

  12. Towards policy relevant environmental modeling: contextual validity and pragmatic models

    USGS Publications Warehouse

    Miles, Scott B.

    2000-01-01

    "What makes for a good model?" In various forms, this question is a question that, undoubtedly, many people, businesses, and institutions ponder with regards to their particular domain of modeling. One particular domain that is wrestling with this question is the multidisciplinary field of environmental modeling. Examples of environmental models range from models of contaminated ground water flow to the economic impact of natural disasters, such as earthquakes. One of the distinguishing claims of the field is the relevancy of environmental modeling to policy and environment-related decision-making in general. A pervasive view by both scientists and decision-makers is that a "good" model is one that is an accurate predictor. Thus, determining whether a model is "accurate" or "correct" is done by comparing model output to empirical observations. The expected outcome of this process, usually referred to as "validation" or "ground truthing," is a stamp on the model in question of "valid" or "not valid" that serves to indicate whether or not the model will be reliable before it is put into service in a decision-making context. In this paper, I begin by elaborating on the prevailing view of model validation and why this view must change. Drawing from concepts coming out of the studies of science and technology, I go on to propose a contextual view of validity that can overcome the problems associated with "ground truthing" models as an indicator of model goodness. The problem of how we talk about and determine model validity has much to do about how we perceive the utility of environmental models. In the remainder of the paper, I argue that we should adopt ideas of pragmatism in judging what makes for a good model and, in turn, developing good models. From such a perspective of model goodness, good environmental models should facilitate communication, convey—not bury or "eliminate"—uncertainties, and, thus, afford the active building of consensus decisions, instead

  13. An animated model of reticulorumen motility.

    PubMed

    Gookin, Jody L; Foster, Derek M; Harvey, Alice M; McWhorter, Dan

    2009-01-01

    Understanding reticulorumen motility is important to the assessment of ruminant health and optimal production, and in the recognition, diagnosis, and treatment of disease. Accordingly, the teaching of reticulorumen motility is a staple of all veterinary curricula. This teaching has historically been based on written descriptions, line drawings, or pressure tracings obtained during contraction sequences. We developed an animated model of reticulorumen motility and hypothesized that veterinary students would prefer use of the model over traditional instructional methods. First-year veterinary students were randomly allocated to one of two online learning exercises: with the animated model (Group A) or with text and line drawings (Group B) depicting reticulorumen motility. Learning was assessed with a multiple-choice quiz and feedback on the learning alternatives was obtained by survey. Seventy-four students participated in the study, including 38/42 in Group A and 36/36 in Group B. Sixty-four out of 72 students (89%) responded that they would prefer use of the animated model if only one of the two learning methods was available. A majority of students agreed or strongly agreed that the animated model was easy to understand and improved their knowledge and appreciation of the importance of reticulorumen motility, and would recommend the model to other veterinary students. Interestingly, students in Group B achieved higher scores on examination than students in Group A. This could be speculatively attributed to the inclusion of an itemized list of contraction sequences in the text provided to Group B and failure of Group A students to read the text associated with the animations.

  14. Animal models for photodynamic therapy (PDT)

    PubMed Central

    Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.

    2015-01-01

    Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. PMID:26415497

  15. Transgenic Animal Models of Huntington's Disease.

    PubMed

    Yang, Shang-Hsun; Chan, Anthony W S

    2011-01-01

    Huntington's disease (HD) is a devastating neurodegenerative disorder that currently has no cure. In order to develop effective treatment, an understanding of HD pathogenesis and the evaluation of therapeutic efficacy of novel medications with the aid of animal models are critical steps. Transgenic animals sharing similar genetic defects that lead to HD have provided important discoveries in HD mechanisms that cell models are not able to replicate, which include psychiatric impairment, cognitive behavioral impact, and motor functions. Although transgenic HD rodent models have been widely used in HD research, it is clear that an animal model with comparable physiology to man, similar genetic defects that lead to HD, and the ability to develop similar cognitive and behavioral impairments is critical for explaining HD pathogenesis and the development of cures. Compared to HD rodents, HD transgenic nonhuman primates have not only developed comparable neuropathology but also present HD clinical features such as rigidity, seizure, dystonia, bradykinesia, and chorea that no other animal model has been able to replicate. Distinctive degenerating neurons and the accumulation of neuropil aggregates observed in HD monkey brain strongly support the hypothesis that the unique neuropathogenic events seen in HD monkey brain recapitulate HD in man. The latest development of transgenic HD primates has opened a new era of animal modeling that better represents human genetic disorders such as HD, which will accelerate the development of diagnostic tools and identifying novel biomarkers through longitudinal studies including gene expression and metabolite profiling, and noninvasive imaging. Furthermore, novel treatments with predictable efficacy in human patients can be developed using HD monkeys because of comparable neuropathology and clinical features.

  16. Animal models for genetic neuromuscular diseases.

    PubMed

    Vainzof, Mariz; Ayub-Guerrieri, Danielle; Onofre, Paula C G; Martins, Poliana C M; Lopes, Vanessa F; Zilberztajn, Dinorah; Maia, Lucas S; Sell, Karen; Yamamoto, Lydia U

    2008-03-01

    The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse

  17. Neonatal animal models of opiate withdrawal.

    PubMed

    Richardson, Kimberlei A; Yohay, Anne-Lise J; Gauda, Estelle B; McLemore, Gabrielle L

    2006-01-01

    The symptoms of opiate withdrawal in infants are defined as neonatal abstinence syndrome (NAS). NAS is a significant cause of morbidity in term and preterm infants. Factors, such as polysubstance abuse, inadequate prenatal care, nutritional deprivation, and the biology of the developing central nervous system contribute to the challenge of evaluating and treating opiate-induced alterations in the newborn. Although research on the effects of opiates in neonatal animal models is limited, the data from adult animal models have greatly contributed to understanding and treating opiate tolerance, addiction, and withdrawal in adult humans. Yet the limited neonatal data that are available indicate that the mechanisms involved in these processes in the newborn differ from those in adult animals, and that neonatal models of opiate withdrawal are needed to understand and develop effective treatment regimens for NAS. In this review, the behavioral and neurochemical evidence from the literature is presented and suggests that mechanisms responsible for opiate tolerance, dependence, and withdrawal differ between adult and neonatal models. Also reviewed are studies that have used neonatal rodent models, the authors' preliminary data based on the use of neonatal rat and mouse models of opiate withdrawal, and other neonatal models that have been proposed for the study of neonatal opiate withdrawal.

  18. Animal models of chronic obstructive pulmonary disease.

    PubMed

    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.

  19. Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

    PubMed Central

    Tashiro, Jun; Rubio, Gustavo A.; Limper, Andrew H.; Williams, Kurt; Elliot, Sharon J.; Ninou, Ioanna; Aidinis, Vassilis; Tzouvelekis, Argyrios; Glassberg, Marilyn K.

    2017-01-01

    Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans. PMID:28804709

  20. The modelling cycle for collective animal behaviour.

    PubMed

    Sumpter, David J T; Mann, Richard P; Perna, Andrea

    2012-12-06

    Collective animal behaviour is the study of how interactions between individuals produce group level patterns, and why these interactions have evolved. This study has proved itself uniquely interdisciplinary, involving physicists, mathematicians, engineers as well as biologists. Almost all experimental work in this area is related directly or indirectly to mathematical models, with regular movement back and forth between models, experimental data and statistical fitting. In this paper, we describe how the modelling cycle works in the study of collective animal behaviour. We classify studies as addressing questions at different levels or linking different levels, i.e. as local, local to global, global to local or global. We also describe three distinct approaches-theory-driven, data-driven and model selection-to these questions. We show, with reference to our own research on species across different taxa, how we move between these different levels of description and how these various approaches can be applied to link levels together.

  1. The modelling cycle for collective animal behaviour

    PubMed Central

    Sumpter, David J. T.; Mann, Richard P.; Perna, Andrea

    2012-01-01

    Collective animal behaviour is the study of how interactions between individuals produce group level patterns, and why these interactions have evolved. This study has proved itself uniquely interdisciplinary, involving physicists, mathematicians, engineers as well as biologists. Almost all experimental work in this area is related directly or indirectly to mathematical models, with regular movement back and forth between models, experimental data and statistical fitting. In this paper, we describe how the modelling cycle works in the study of collective animal behaviour. We classify studies as addressing questions at different levels or linking different levels, i.e. as local, local to global, global to local or global. We also describe three distinct approaches—theory-driven, data-driven and model selection—to these questions. We show, with reference to our own research on species across different taxa, how we move between these different levels of description and how these various approaches can be applied to link levels together. PMID:23173077

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

    PubMed

    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.

  3. Cholestasis: human disease and experimental animal models.

    PubMed

    Rodríguez-Garay, Emilio Alberto

    2003-01-01

    Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common. Other types of cholestasis seen in humans are a group of familial cholestatic disorders, obstructive cholestasis, primary biliary cirrhosis, extrahepatic biliary atresia, primary sclerosing cholangitis, cholestasis of pregnancy, oral contraceptive-induced cholestasis, and sepsis-induced cholestasis. Experimental animal models allow the understanding of pathophysiological mechanisms involved and their clinical correlates. The most common experimental models of intrahepatic cholestasis are estrogen-induced, endotoxin-induced and drug-induced cholestasis. A well known model of extrahepatic biliary obstruction is common bile duct ligation. Drug-induced cholestasis were described using different drugs. On this regard, alpha naphthylisothiocyanate treatment has been extensively used, permitting to describe not only cholestatic alterations but also compensatory mechanisms. Congenital defficiency of transport proteins also were studied in natural rat models of cholestasis. The experimental animal models allow to define down-regulated alterations of hepatocyte transport proteins, and up-regulated ones acting as compensatory mechanisms. In conclusion, animal model and transport protein studies are necessary for the progressive understanding of congenital and acquired human cholestasis, and regulatory mechanisms that operate on liver cells.

  4. Animal models of psoriasis and pustular psoriasis.

    PubMed

    Mizutani, Hitoshi; Yamanaka, Keiichi; Konishi, Hiroshi; Murakami, Takaaki

    2003-04-01

    Investigation of psoriasis and pustular psoriasis is presently hampered by the lack of appropriate animal models. So far, more than ten models have been developed in mice by spontaneous gene mutations and by gene manipulation. However, none of them has satisfactorily reproduced the clinicopathological and immunopathological phenotypes of these diseases. Xenotransplantation techniques have been used for designing models of psoriasis vulgaris, in which CD4(+) T cells have been shown to play an important role. An ideal model for pustular psoriasis should have an immunological background and fulfill the diagnostic criteria of psoriasis.

  5. Potential animal models of seasonal affective disorder.

    PubMed

    Workman, Joanna L; Nelson, Randy J

    2011-01-01

    Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.

  6. Nonmurine animal models of food allergy.

    PubMed

    Helm, Ricki M; Ermel, Richard W; Frick, Oscar L

    2003-02-01

    Food allergy can present as immediate hypersensitivity [manifestations mediated by immunoglobulin (Ig)E], delayed-type hypersensitivity (reactions associated with specific T lymphocytes), and inflammatory reactions caused by immune complexes. For reasons of ethics and efficacy, investigations in humans to determine sensitization and allergic responses of IgE production to innocuous food proteins are not feasible. Therefore, animal models are used a) to bypass the innate tendency to develop tolerance to food proteins and induce specific IgE antibody of sufficient avidity/affinity to cause sensitization and upon reexposure to induce an allergic response, b) to predict allergenicity of novel proteins using characteristics of known food allergens, and c) to treat food allergy by using immunotherapeutic strategies to alleviate life-threatening reactions. The predominant hypothesis for IgE-mediated food allergy is that there is an adverse reaction to exogenous food proteins or food protein fragments, which escape lumen hydrolysis, and in a polarized helper T cell subset 2 (Th2) environment, immunoglobulin class switching to allergen-specific IgE is generated in the immune system of the gastrointestinal-associated lymphoid tissues. Traditionally, the immunologic characterization and toxicologic studies of small laboratory animals have provided the basis for development of animal models of food allergy; however, the natural allergic response in large animals, which closely mimic allergic diseases in humans, can also be useful as models for investigations involving food allergy.

  7. Animal model of reversible, right ventricular failure.

    PubMed

    McKellar, Stephen H; Javan, Hadi; Bowen, Megan E; Liu, Xiaoquing; Schaaf, Christin L; Briggs, Casey M; Zou, Huashan; Gomez, Arnold David; Abdullah, Osama M; Hsu, Ed W; Selzman, Craig H

    2015-04-01

    Heart failure is a leading cause of death but very little is known about right ventricular (RV) failure (RVF) and right ventricular recovery (RVR). A robust animal model of reversible, RVF does not exist, which currently limits research opportunities and clinical progress. We sought to develop an animal model of reversible, pressure-overload RVF to study RVF and RVR. Fifteen New Zealand rabbits underwent implantation of a fully implantable, adjustable, pulmonary artery band. Animals were assigned to the control, RVF, and RVR groups (n = 5 for each). For the RVF and RVR groups, the pulmonary artery bands were serially tightened to create RVF and released for RVR. Echocardiographic, cardiac magnetic resonance imaging, and histologic analysis were performed. RV chamber size and wall thickness increased during RVF and regressed during RVR. RV volumes were 1023 μL ± 123 for control, 2381 μL ± 637 for RVF, and 635 μL ± 549 for RVR, and RV wall thicknesses were 0.98 mm ± 0.12 for controls (P = 0.05), 1.72 mm ± 0.60 for RVF, and 1.16 mm ± 0.03 for RVR animals (P = 0.04), respectively. Similarly, heart weight, liver weight, cardiomyocyte size, and the degree of cardiac and hepatic fibrosis increased with RVF and decreased during RVR. We report an animal model of chronic, reversible, pressure-overload RVF to study RVF and RVR. This model will be used for preclinical studies that improve our understanding of the mechanisms of RVF and that develop and test RV protective and RVR strategies to be studied later in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Vestibular animal models: contributions to understanding physiology and disease.

    PubMed

    Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

    2016-04-01

    Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

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

    PubMed Central

    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

  10. Pathogenesis of Epilepsy: Challenges in Animal Models

    PubMed Central

    Hui Yin, Yow; Ahmad, Nurulumi; Makmor-Bakry, Mohd

    2013-01-01

    Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models. PMID:24494063

  11. Animal models of coronary heart disease.

    PubMed

    Liao, Jiawei; Huang, Wei; Liu, George

    2015-08-20

    Cardiovascular disease, predominantly coronary heart disease and stroke, leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions. The dominant pathologic foundation for cardiovascular disease is atherosclerosis and as to coronary heart disease, coronary atherosclerosis and resulting lumen stenosis, even total occlusions. In translational research, several animals, such as mice, rabbits and pigs, have been used as disease models of human atherosclerosis and related cardiovascular disorders. However, coronary lesions are either naturally rare or hard to be fast induced in these models, hence, coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions, thus unrepresentative of human coronary heart disease progression and pathology. In this review, we will describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

  12. Animal models of enteroaggregative Escherichia coli infection

    PubMed Central

    Philipson, Casandra W.; Bassaganya-Riera, Josep; Hontecillas, Raquel

    2013-01-01

    Enteroaggregative Escherichia coli (EAEC) has been acknowledged as an emerging cause of gastroenteritis worldwide for over two decades. Epidemiologists are revealing the role of EAEC in diarrheal outbreaks as a more common occurrence than ever suggested before. EAEC induced diarrhea is most commonly associated with travelers, children and immunocompromised individuals however its afflictions are not limited to any particular demographic. Many attributes have been discovered and characterized surrounding the capability of EAEC to provoke a potent pro-inflammatory immune response, however cellular and molecular mechanisms underlying initiation, progression and outcomes are largely unknown. This limited understanding can be attributed to heterogeneity in strains and the lack of adequate animal models. This review aims to summarize current knowledge about EAEC etiology, pathogenesis and clinical manifestation. Additionally, current animal models and their limitations will be discussed along with the value of applying systems-wide approaches such as computational modeling to study host-EAEC interactions. PMID:23680797

  13. Animal models of insulin resistance: A review.

    PubMed

    Sah, Sangeeta Pilkhwal; Singh, Barinder; Choudhary, Supriti; Kumar, Anil

    2016-12-01

    Insulin resistance can be seen as a molecular and genetic mystery, with a role in the pathophysiology of type 2 diabetes mellitus. It is a basis for a number of chronic diseases like hypertension, dyslipidemia, glucose intolerance, coronary heart disease, cerebral vascular disease along with T2DM, thus the key is to cure and prevent insulin resistance. Critical perspicacity into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by various transgenic and non-transgenic models which is not possible in human studies. The following review comprises the pathophysiology involved in insulin resistance, various factors causing insulin resistance, their screening and various genetic and non-genetic animal models highlighting the pathological and metabolic characteristics of each.

  14. Animal models of acute renal failure.

    PubMed

    Singh, Amrit Pal; Junemann, Anselm; Muthuraman, Arunachalam; Jaggi, Amteshwar Singh; Singh, Nirmal; Grover, Kuldeep; Dhawan, Ravi

    2012-01-01

    The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.

  15. Animal models of anxiety disorders and stress.

    PubMed

    Campos, Alline C; Fogaça, Manoela V; Aguiar, Daniele C; Guimarães, Francisco S

    2013-01-01

    Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents). The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as "ethological" the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field), whereas models that involve learned/punished responses are referred to as "conditioned operant conflict tests" (such as the Vogel conflict test). We also discussed models that involve mainly classical conditioning tests (fear conditioning). Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress), physical (restraint stress), and chronic unpredictable stress.

  16. Service and Emotional Support Animals on Campus: The Relevance and Controversy

    ERIC Educational Resources Information Center

    Phillips, Melinda

    2016-01-01

    Service and emotional support animals (ESA) have recently been a topic of conversation on college campuses, despite decades of controversy related to the interpretation of federal law. The distinction between an Emotional Support Animal and Service Animals, and the rights of the student regarding accommodations under FHA and ADA have been debated…

  17. Cardiovascular imaging: what have we learned from animal models?

    PubMed Central

    Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A.; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús

    2015-01-01

    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 non-destructive 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. PMID:26539113

  18. Cardiovascular imaging: what have we learned from animal models?

    PubMed

    Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús

    2015-01-01

    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 non-destructive 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.

  19. Animal Models of Depression: Molecular Perspectives

    PubMed Central

    Krishnan, Vaishnav; Nestler, Eric J.

    2012-01-01

    Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression. PMID:21225412

  20. Animal model validation studies. Final report

    SciTech Connect

    Frazer, D.G.

    1989-01-01

    The project objectives were the development of a system to be used for exposing small laboratory animals to the respirable fraction of cotton dust found in a cotton mill, and testing an animal model of byssinosis which could be used to study the development of the disease in humans. This final report contains 10 published papers of the research at various stages of completion. A description of the cotton dust exposure system optimization techniques and measurements of the resulting improvements are noted in these articles. The final system developed used a large, modified, Pitt-3 cotton generator to expose up to 10 animals simultaneously to cotton dust in a Wahman stainless steel chamber. The acoustical powered generator, which was developed for the project to resuspend cotton dust has been very useful in resuspending other agricultural dusts. The development of an animal model for byssinosis involved verifying results of other investigators, developing and testing several new methods to evaluate pulmonary function in guinea pigs following acute cotton dust exposures, and modification of the cotton dust response using drug mediators.

  1. Animal models of viral hemorrhagic fever.

    PubMed

    Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

    2014-12-01

    The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures.

  2. Towards an animal model of food addiction.

    PubMed

    de Jong, Johannes W; Vanderschuren, Louk J M J; Adan, Roger A H

    2012-01-01

    The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes, poses an enormous public health problem. It has been proposed that the obesity epidemic can be explained by the concept of 'food addiction'. In this review we focus on possible similarities between binge eating disorder (BED), which is highly prevalent in the obese population, and drug addiction. Indeed, both behavioral and neural similarities between addiction and BED have been demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV criteria for drug addiction with the (suggested) criteria for BED and by food addiction-like behavior in animals after prolonged intermittent access to palatable food. Neural similarities include the overlap in brain regions involved in food and drug craving. Decreased dopamine D2 receptor availability in the striatum has been found in animal models of binge eating, after cocaine self-administration in animals as well as in drug addiction and obesity in humans. To further explore the neurobiological basis of food addiction, it is essential to have an animal model to test the addictive potential of palatable food. A recently developed animal model for drug addiction involves three behavioral characteristics that are based on the DSM-IV criteria: i) extremely high motivation to obtain the drug, ii) difficulty in limiting drug seeking even in periods of explicit non-availability, iii) continuation of drug-seeking despite negative consequences. Indeed, it has been shown that a subgroup of rats, after prolonged cocaine self-administration, scores positive on these three criteria. If food possesses addictive properties, then food-addicted rats should also meet these criteria while searching for and consuming food. In this review we discuss evidence from literature regarding food addiction-like behavior. We also suggest future experiments that could

  3. Incorporating Relevance and Psuedo-Relevance Feedback in the Markov Random Field Model

    DTIC Science & Technology

    2008-11-01

    i.e. relevant) feedback documents: Θ̂F = 1 |F| ∑ D∈F ΘD (4) While the classic Rocchio method ( Rocchio & others 1971) also incorporates negative...participating systems that em- ployed one or the other. Use of negative feedback (e.g. via Rocchio ) generally provided little benefit. Interest- ingly, all of...and Croft, W. B. 1998. A language modeling approach to information retrieval. In Proc. of SIGIR, 275– 281. Rocchio , J., et al. 1971. Relevance

  4. Microparticles and cancer thrombosis in animal models.

    PubMed

    Mege, Diane; Mezouar, Soraya; Dignat-George, Françoise; Panicot-Dubois, Laurence; Dubois, Christophe

    2016-04-01

    Cancer-associated venous thromboembolism (VTE) constitutes the second cause of death after cancer. Many risk factors for cancer-associated VTE have been identified, among them soluble tissue factor and microparticles (MPs). Few data are available about the implication of MPs in cancer associated-VTE through animal model of cancer. The objective of the present review was to report the state of the current literature about MPs and cancer-associated VTE in animal model of cancer. Fourteen series have reported the role of MPs in cancer-associated VTE, through three main mouse models: ectopic or orthotopic tumor induction, experimental metastasis by intravenous injection of tumor cells into the lateral tail vein of the mouse. Pancreatic cancer is the most used animal model, due to its high rate of cancer-associated VTE. All the series reported that tumor cell-derived MPs can promote thrombus formation in TF-dependent manner. Some authors reported also the implication of phosphatidylserine and PSGL1 in the generation of thrombin. Moreover, MPs seem to be implicated in cancer progression through a coagulation-dependent mechanism secondary to thrombocytosis, or a mechanism implicating the regulation of the immune response. For these reasons, few authors have reported that antiplatelet and anticoagulant treatments may prevent tumor progression and the formation of metastases in addition of coagulopathy. © 2016 Elsevier Ltd. All rights reserved.

  5. Experimental animal modelling for TB vaccine development.

    PubMed

    Cardona, Pere-Joan; Williams, Ann

    2017-03-01

    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. Copyright © 2017. Published by Elsevier Ltd.

  6. Models of GH deficiency in animal studies.

    PubMed

    Gahete, Manuel D; Luque, Raul M; Castaño, Justo P

    2016-12-01

    Growth hormone (GH) is a peptide hormone released from pituitary somatotrope cells that promotes growth, cell division and regeneration by acting directly through the GH receptor (GHR), or indirectly via hepatic insulin-like growth factor 1 (IGF1) production. GH deficiency (GHD) can cause severe consequences, such as growth failure, changes in body composition and altered insulin sensitivity, depending of the origin, time of onset (childhood or adulthood) or duration of GHD. The highly variable clinical phenotypes of GHD can now be better understood through research on transgenic and naturally-occurring animal models, which are widely employed to investigate the origin, phenotype, and consequences of GHD, and particularly the underlying mechanisms of metabolic disorders associated to GHD. Here, we reviewed the most salient aspects of GH biology, from somatotrope development to GH actions, linked to certain GHD types, as well as the animal models employed to reproduce these GHD-associated alterations.

  7. Standardised animal models of host microbial mutualism

    PubMed Central

    Macpherson, A J; McCoy, K D

    2015-01-01

    An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions. PMID:25492472

  8. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

    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.

  9. Experimental Diabetes Mellitus in Different Animal Models.

    PubMed

    Al-Awar, Amin; Kupai, Krisztina; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

  10. Animal models of age related macular degeneration

    PubMed Central

    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

  11. Modeling Behavior and Variation for Crowd Animation

    DTIC Science & Technology

    2009-08-01

    Modeling Behavior and Variation for Crowd Animation Manfred Chung Man Lau CMU-CS-09-148 August 2009 School of Computer Science Carnegie Mellon...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Carnegie Mellon University , School of Computer Science,Pittsburgh,PA,15213 8. PERFORMING ORGANIZATION...fast crowds on ps3. In sandbox ’06: Proceedings of the 2006 ACM SIGGRAPH symposium on Videogames , pages 113–121, 2006. 2.1 [87] Craig W. Reynolds

  12. Animal models of ANCA associated vasculitis

    PubMed Central

    Salama, Alan D.; Little, Mark A

    2012-01-01

    This review seeks to provide an update on the experimental models that have been developed recapitulating clinical ANCA associated vasculitis. The recent insights regarding the application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. Recent findings Rodent models of both MPO- and PR3 ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA associated pulmonary and renal disease. The vast majority of in vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in modelling of anti-PR3 disease. As with all experimental animal models they are flawed in one way or another, by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener’s), or the development of vasculitis lesions in organs other than the lungs or kidneys. However, use of a combination of the available models should allow greater understanding of the critical requirements for disease and how these may be potentially monitored and modified in patients. Summary ANCA associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on use of molecular blocking agents and transgenic animals to elucidate disease pathways. PMID:22089094

  13. Technical intelligence in animals: the kea model.

    PubMed

    Huber, Ludwig; Gajdon, Gyula K

    2006-10-01

    The ability to act on information flexibly is one of the cornerstones of intelligent behavior. As particularly informative example, tool-oriented behavior has been investigated to determine to which extent nonhuman animals understand means-end relations, object affordances, and have specific motor skills. Even planning with foresight, goal-directed problem solving and immediate causal inference have been a focus of research. However, these cognitive abilities may not be restricted to tool-using animals but may be found also in animals that show high levels of curiosity, object exploration and manipulation, and extractive foraging behavior. The kea, a New Zealand parrot, is a particularly good example. We here review findings from laboratory experiments and field observations of keas revealing surprising cognitive capacities in the physical domain. In an experiment with captive keas, the success rate of individuals that were allowed to observe a trained conspecific was significantly higher than that of naive control subjects due to their acquisition of some functional understanding of the task through observation. In a further experiment using the string-pulling task, a well-probed test for means-end comprehension, we found the keas finding an immediate solution that could not be improved upon in nine further trials. We interpreted their performance as insightful in the sense of being sensitive of the relevant functional properties of the task and thereby producing a new adaptive response without trial-and-error learning. Together, these findings contribute to the ongoing debate on the distribution of higher cognitive skills in the animal kingdom by showing high levels of sensorimotor intelligence in animals that do not use tools. In conclusion, we suggest that the 'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II: extensions and evaluations, pp 289-211, 1997), which has been proposed to explain the origin of the ape/monkey grade-shift in

  14. Risk of parasite transmission influences perceived vulnerability to disease and perceived danger of disease-relevant animals.

    PubMed

    Prokop, Pavol; Usak, Muhammet; Fancovicová, Jana

    2010-09-01

    Adaptationist view proposes that emotions were shaped by natural selection and their primary function is to protect humans against predators and/or disease threat. This study examined cross-cultural and inter-personal differences in behavioural immune system measured by disgust, fear and perceived danger in participants from high (Turkey) and low (Slovakia) pathogen prevalence areas. We found that behavioural immune system in Turkish participants was activated more than those of Slovakian participants when exposed to photographs depicting disease-relevant cues, but not when exposed to disease-irrelevant cues. However, participants from Slovakia, where human to human disease transmission is expected to be more prevalent than in Turkey, showed lower aversion in Germ Aversion subscale supporting hypersensitiveness of the behavioural immune system. Having animals at home was less frequent both in Turkey and in participants who perceived higher danger about disease relevant animals. Participants more vulnerable to diseases reported higher incidence of illness last year and considered perceived disease-relevant animals more dangerous than others. Females showed greater fear, disgust and danger about disease-relevant animals than males. Our results further support the finding that cultural and inter-personal differences in human personality are influenced by parasite threat.

  15. Animal models of compulsive eating behavior.

    PubMed

    Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella

    2014-10-22

    Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.

  16. Colon Preneoplastic Lesions in Animal Models

    PubMed Central

    Suzui, Masumi; Morioka, Takamitsu; Yoshimi, Naoki

    2013-01-01

    The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions. PMID:24526805

  17. The Laboratory Rat as an Animal Model for Osteoporosis Research

    PubMed Central

    Lelovas, Pavlos P; Xanthos, Theodoros T; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A

    2008-01-01

    Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome through detailed knowledge of its specific traits or with certain techniques. The rat has been used in many experimental protocols leading to bone loss, including hormonal interventions (ovariectomy, orchidectomy, hypophysectomy, parathyroidectomy), immobilization, and dietary manipulations. The aim of the current review is not only to present the ovariectomized rat and its advantages as an appropriate model for the research of osteoporosis, but also to provide information about the most relevant age and bone site selection according to the goals of each experimental protocol. In addition, several methods of bone mass evaluation are assessed, such as biochemical markers, densitometry, histomorphometry, and bone mechanical testing, that are used for monitoring and evaluation of this animal model in preventive or therapeutic strategies for osteoporosis. PMID:19004367

  18. Animal Models for Medical Countermeasures to Radiation Exposure

    PubMed Central

    Williams, Jacqueline P.; Brown, Stephen L.; Georges, George E.; Hauer-Jensen, Martin; Hill, Richard P.; Huser, Amy K.; Kirsch, David G.; MacVittie, Thomas J.; Mason, Kathy A.; Medhora, Meetha M.; Moulder, John E.; Okunieff, Paul; Otterson, Mary F.; Robbins, Michael E.; Smathers, James B.; McBride, William H.

    2011-01-01

    Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the “Animal Rule” from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings. PMID:20334528

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

    PubMed

    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.

  20. Humanized animal exercise model for clinical implication.

    PubMed

    Seo, Dae Yun; Lee, Sung Ryul; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2014-09-01

    Exercise and physical activity function as a patho-physiological process that can prevent, manage, and regulate numerous chronic conditions, including metabolic syndrome and age-related sarcopenia. Because of research ethics and technical difficulties in humans, exercise models using animals are requisite for the future development of exercise mimetics to treat such abnormalities. Moreover, the beneficial or adverse outcomes of a new regime or exercise intervention in the treatment of a specific condition should be tested prior to implementation in a clinical setting. In rodents, treadmill running (or swimming) and ladder climbing are widely used as aerobic and anaerobic exercise models, respectively. However, exercise models are not limited to these types. Indeed, there are no golden standard exercise modes or protocols for managing or improving health status since the types (aerobic vs. anaerobic), time (morning vs. evening), and duration (continuous vs. acute bouts) of exercise are the critical determinants for achieving expected beneficial effects. To provide insight into the understanding of exercise and exercise physiology, we have summarized current animal exercise models largely based on aerobic and anaerobic criteria. Additionally, specialized exercise models that have been developed for testing the effect of exercise on specific physiological conditions are presented. Finally, we provide suggestions and/or considerations for developing a new regime for an exercise model.

  1. Animal Models Utilized in HTLV-1 Research

    PubMed Central

    Panfil, Amanda R; Al-Saleem, Jacob J; Green, Patrick L

    2013-01-01

    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. PMID:25512694

  2. Animal Models Utilized in HTLV-1 Research.

    PubMed

    Panfil, Amanda R; Al-Saleem, Jacob J; Green, Patrick L

    2013-01-01

    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.

  3. Physiology of female sexual function: animal models.

    PubMed

    Giraldi, Annamaria; Marson, Lesley; Nappi, Rossella; Pfaus, James; Traish, Abdulmaged M; Vardi, Yoram; Goldstein, Irwin

    2004-11-01

    Data concerning the physiology of desire, arousal, and orgasm in women are limited because of ethical constraints. Aim. To gain knowledge of physiology of female sexual function through animal models. To provide state-of-the-art knowledge concerning female sexual function in animal models, representing the opinions of seven experts from five countries developed in a consensus process over a 2-year period. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. Sexual desire may be considered as the presence of desire for, and fantasy about, sexual activity. Desire in animals can be inferred from certain appetitive behaviors that occur during copulation and from certain unconditioned copulatory measures. Proceptive behaviors are dependent in part on estrogen, progesterone, and drugs that bind to D1 dopamine receptors, adrenergic receptors, oxytocin receptors, opioid receptors, or gamma-amino butyric acid receptors. Peripheral arousal states are dependent on regulation of genital smooth muscle tone. Multiple neurotransmitters/mediators are involved including adrenergic, and nonadrenergic, noncholinergic agents such as vasoactive intestinal polypeptide, nitric oxide, neuropeptide Y, calcitonin gene-related peptide, and substance P. Sex steroid hormones, estrogens and androgens, are critical for structure and function of genital tissues including modulation of genital blood flow, lubrication, neurotransmitter function, smooth muscle contractility, mucification, and sex steroid receptor expression in genital tissues. Orgasm may be investigated by urethrogenital (UG) reflex, in which genital stimulation results in rhythmic contractions of striated perineal muscles and contractions of vagina, anus, and uterine smooth muscle. The UG reflex is generated by a multisegmental spinal pattern generator involving the coordination of sympathetic, parasympathetic, and somatic efferents

  4. A Compositional Relevance Model for Adaptive Information Retrieval

    NASA Technical Reports Server (NTRS)

    Mathe, Nathalie; Chen, James; Lu, Henry, Jr. (Technical Monitor)

    1994-01-01

    There is a growing need for rapid and effective access to information in large electronic documentation systems. Access can be facilitated if information relevant in the current problem solving context can be automatically supplied to the user. This includes information relevant to particular user profiles, tasks being performed, and problems being solved. However most of this knowledge on contextual relevance is not found within the contents of documents, and current hypermedia tools do not provide any easy mechanism to let users add this knowledge to their documents. We propose a compositional relevance network to automatically acquire the context in which previous information was found relevant. The model records information on the relevance of references based on user feedback for specific queries and contexts. It also generalizes such information to derive relevant references for similar queries and contexts. This model lets users filter information by context of relevance, build personalized views of documents over time, and share their views with other users. It also applies to any type of multimedia information. Compared to other approaches, it is less costly and doesn't require any a priori statistical computation, nor an extended training period. It is currently being implemented into the Computer Integrated Documentation system which enables integration of various technical documents in a hypertext framework.

  5. A Compositional Relevance Model for Adaptive Information Retrieval

    NASA Technical Reports Server (NTRS)

    Mathe, Nathalie; Chen, James; Lu, Henry, Jr. (Technical Monitor)

    1994-01-01

    There is a growing need for rapid and effective access to information in large electronic documentation systems. Access can be facilitated if information relevant in the current problem solving context can be automatically supplied to the user. This includes information relevant to particular user profiles, tasks being performed, and problems being solved. However most of this knowledge on contextual relevance is not found within the contents of documents, and current hypermedia tools do not provide any easy mechanism to let users add this knowledge to their documents. We propose a compositional relevance network to automatically acquire the context in which previous information was found relevant. The model records information on the relevance of references based on user feedback for specific queries and contexts. It also generalizes such information to derive relevant references for similar queries and contexts. This model lets users filter information by context of relevance, build personalized views of documents over time, and share their views with other users. It also applies to any type of multimedia information. Compared to other approaches, it is less costly and doesn't require any a priori statistical computation, nor an extended training period. It is currently being implemented into the Computer Integrated Documentation system which enables integration of various technical documents in a hypertext framework.

  6. Freshwater Planarians as an Alternative Animal Model for Neurotoxicology

    PubMed Central

    Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S.

    2015-01-01

    Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment “at will” through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. PMID:26116028

  7. Freshwater Planarians as an Alternative Animal Model for Neurotoxicology.

    PubMed

    Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S

    2015-09-01

    Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models.

  8. Methicillin-Resistant Staphylococcus aureus Associated with Animals and Its Relevance to Human Health

    PubMed Central

    Pantosti, Annalisa

    2012-01-01

    Staphylococcus aureus is a typical human pathogen. Some animal S. aureus lineages have derived from human strains following profound genetic adaptation determining a change in host specificity. Due to the close relationship of animals with the environmental microbiome and resistome, animal staphylococcal strains also represent a source of resistance determinants. Methicillin-resistant S. aureus (MRSA) emerged 50 years ago as a nosocomial pathogen but in the last decade it has also become a frequent cause of infections in the community. The recent finding that MRSA frequently colonizes animals, especially livestock, has been a reason for concern, as it has revealed an expanded reservoir of MRSA. While MRSA strains recovered from companion animals are generally similar to human nosocomial MRSA, MRSA strains recovered from food animals appear to be specific animal-adapted clones. Since 2005, MRSA belonging to ST398 was recognized as a colonizer of pigs and human subjects professionally exposed to pig farming. The “pig” MRSA was also found to colonize other species of farmed animals, including horses, cattle, and poultry and was therefore designated livestock-associated (LA)-MRSA. LA-MRSA ST398 can cause infections in humans in contact with animals, and can infect hospitalized people, although at the moment this occurrence is relatively rare. Other animal-adapted MRSA clones have been detected in livestock, such as ST1 and ST9. Recently, ST130 MRSA isolated from bovine mastitis has been found to carry a novel mecA gene that eludes detection by conventional PCR tests. Similar ST130 strains have been isolated from human infections in UK, Denmark, and Germany at low frequency. It is plausible that the increased attention to animal MRSA will reveal other strains with peculiar characteristics that can pose a risk to human health. PMID:22509176

  9. An animal model to study regenerative endodontics.

    PubMed

    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.

  10. Animal models of addiction: fat and sugar.

    PubMed

    Morgan, Drake; Sizemore, Glen M

    2011-01-01

    The concept of "food addiction" is gaining acceptance among the scientific community, and much is known about the influence of various components of food (e.g. high-fat, sugar, carbohydrate, salt) on behavior and physiology. Most of the studies to date have studied these consequences following relatively long-term diet manipulations and/or relatively free access to the food of interest. It is suggested that these types of studies are primarily tapping into the energy regulation and homeostatic processes that govern food intake and consumption. More recently, the overlap between the neurobiology of "reward-related" or hedonic effects of food ingestion and other reinforcers such as drugs of abuse has been highlighted, contributing to the notion that "food addiction" exists and that various components of food may be the substance of abuse. Based on preclinical animal models of drug addiction, a new direction for this field is using self-administration procedures and identifying an addiction-like behavioral phenotype in animals following various environmental, genetic, pharmacological, and neurobiological manipulations. Here we provide examples from this research area, with a focus on fat and sugar self-administration, and how the sophisticated animal models of drug addiction can be used to study the determinants and consequences of food addiction.

  11. An animal model of autoimmune emphysema.

    PubMed

    Taraseviciene-Stewart, Laimute; Scerbavicius, Robertas; Choe, Kang-Hyeon; Moore, Melissa; Sullivan, Andrew; Nicolls, Mark R; Fontenot, Andrew P; Tuder, Rubin M; Voelkel, Norbert F

    2005-04-01

    Although cigarette smoking is implicated in the pathogenesis of emphysema, the precise mechanisms of chronic progressive alveolar septal destruction are not well understood. We show, in a novel animal model, that immunocompetent, but not athymic, nude rats injected intraperitoneally with xenogeneic endothelial cells (ECs) produce antibodies against ECs and develop emphysema. Immunization with ECs also leads to alveolar septal cell apoptosis and activation of matrix metalloproteases MMP-9 and MMP-2. Anti-EC antibodies cause EC apoptosis in vitro and emphysema in passively immunized mice. Moreover, immunization also causes accumulation of CD4+ T cells in the lung. Adoptive transfer of pathogenic, spleen-derived CD4+ cells into naive immunocompetent animal also results in emphysema. This study shows for the first time that humoral- and CD4+ cell-dependent mechanisms are sufficient to trigger the development of emphysema, suggesting that alveolar septal cell destruction might result from immune mechanisms.

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

    PubMed

    Herati, Ramin Sedaghat; Wherry, E John

    2017-03-27

    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.

  13. Sexual Differentiation of the Brain in Man and Animals: Of Relevance to Klinefelter Syndrome?

    PubMed Central

    McCarthy, MARGARET M.

    2017-01-01

    The developing brain is highly sensitive to the organizing effects of steroids of gonadal origin in a process referred to as sexual differentiation. Early hormone effects prime the brain for adult sensitivity to the appropriate hormonal milieu, maximizing reproductive fitness via coordinated physiology and behavior. Animal models, in particular rodents, have provided insight into general principles and the cellular and molecular mechanisms of brain differentiation. Cellular endpoints influenced by steroids in the developing brain include neurogenesis, migration, apoptosis, dendritic growth, and synaptic patterning. Important roles for prostaglandins, endocanabinoids, and epigenetics are among the many cellular mediators of hormonal organization. Transference of general principles of brain sexual differentiation to humans relies on observations of individuals with genetic anomalies that either increase or decrease hormone exposure and sensitivity. The physiology and behavior of individuals with XXY (Klinefelter syndrome) has not been considered in the context of sexual differentiation of the brain, most likely due to the delay in diagnoses and highly variable presentation. The behavioral phenotype and impairments in the domains of speech and language that are characteristic of individuals with XXY is consistent with the reduced androgen production associated with the syndrome. Hormone replacement appears effective in restoring some deficits and impact may be further improved by increased understanding of the hormonally mediated sexual differentiation of the brain. PMID:23335108

  14. Hidden process models for animal population dynamics.

    PubMed

    Newman, K B; Buckland, S T; Lindley, S T; Thomas, L; Fernández, C

    2006-02-01

    Hidden process models are a conceptually useful and practical way to simultaneously account for process variation in animal population dynamics and measurement errors in observations and estimates made on the population. Process variation, which can be both demographic and environmental, is modeled by linking a series of stochastic and deterministic subprocesses that characterize processes such as birth, survival, maturation, and movement. Observations of the population can be modeled as functions of true abundance with realistic probability distributions to describe observation or estimation error. Computer-intensive procedures, such as sequential Monte Carlo methods or Markov chain Monte Carlo, condition on the observed data to yield estimates of both the underlying true population abundances and the unknown population dynamics parameters. Formulation and fitting of a hidden process model are demonstrated for Sacramento River winter-run chinook salmon (Oncorhynchus tshawytsha).

  15. Exploiting ovine immunology to improve the relevance of biomedical models

    PubMed Central

    Entrican, Gary; Wattegedera, Sean R.; Griffiths, David J.

    2015-01-01

    Animal models of human disease are important tools in many areas of biomedicine; for example, in infectious disease research and in the development of novel drugs and medical devices. Most studies involving animals use rodents, in particular congenic mice, due to the availability of a wide number of strains and the ease with which they can be genetically manipulated. The use of mouse models has led to major advances in many fields of research, in particular in immunology but despite these advances, no animal model can exactly reproduce all the features of human disease. It is increasingly becoming recognised that in many circumstances mice do not provide the best model and that alternative species may be more appropriate. Here, we describe the relative merits of sheep as biomedical models for human physiology and disease in comparison to mice, with a particular focus on reproductive and respiratory pathogens. PMID:25263932

  16. Animal modelling for inherited central vision loss.

    PubMed

    Kostic, Corinne; Arsenijevic, Yvan

    2016-01-01

    Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans.

  17. Animal models of nonconvulsive status epilepticus.

    PubMed

    Hosford, D A

    1999-07-01

    Nonconvulsive status epilepticus includes three clinical situations: complex partial status epilepticus; absence status epilepticus: and obtundation in the presence of electrographic status epilepticus. Animal models that provide information helpful to clinical management exist for both complex partial and absence status epilepticus. In models of complex partial status epilepticus (pilocarpine, kainic acid, and various protocols using electrical stimulation), neuronal damage in discrete neuronal populations follows an episode of status epilepticus. Hippocampal populations are particularly susceptible to neuropathologic sequelae. Although it is difficult in some cases to distinguish whether the inducing agent or the status epilepticus causes neuropathology, the similar patterns of damage caused by different inducing stimuli provide converging lines of evidence suggesting that the neuropathologic consequences stem at least in part from status epilepticus. In models of absence status epilepticus (genetic mutants, pentylenetetrazole), there is relatively scarce neuropathology that can be attributed directly to status epilepticus. Together these data from animal models suggest that neuropathologic consequences from complex partial status epilepticus may be more severe than those from absence status epilepticus. If these findings translate to patients, then nonconvulsive status epilepticus of the complex partial type should be managed more aggressively than nonconvulsive status epilepticus of the absence type.

  18. Animal models for HIV/AIDS research

    PubMed Central

    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

  19. Neural circuit dysfunction in schizophrenia: Insights from animal models.

    PubMed

    Sigurdsson, T

    2016-05-03

    Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Molecular diagnosis of certain nematode infections can save life and beauty, and preserve breeds of socially relevant and sporting animals.

    PubMed

    Traversa, Donato

    2007-11-30

    The recognition that the health and welfare of some humans are improved through contact and relationships with animals is now established. Two commonly recognized assistance animals are dogs and horses. Both provide therapeutic benefits to humans with some physical and mental illnesses and both assist people with disabilities. Moreover, the public and scientific attention to the health and conservation of many animal breeds is also increasing worldwide. In the past few years, two potentially life-threatening nematode infections that can induce tumours or tumour-like masses in canids and equids, spirocercosis and draschiosis/habronemosis, respectively, are emerging in several areas of the world. This article reviews and comments how recent insights into the molecular early diagnosis of these diseases can save and preserve life, beauty and breeds of socially relevant and sporting animals.

  1. Contribution of animal models to contemporary understanding of Attention Deficit Hyperactivity Disorder.

    PubMed

    Carvalho, Constança; Vieira Crespo, Mariana; Ferreira Bastos, Luisa; Knight, Andrew; Vicente, Luís

    2016-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a poorly understood neurodevelopmental disorder of multifactorial origin. Animal-based research has been used to investigate ADHD aetiology, pathogenesis and treatment, but the efficacy of this research for patients has not yet been systematically evaluated. However, such evaluation is important, given the resource consumption and ethical concerns incurred by animal use. Accordingly, we used the citation tracking facility within Web of Science to locate original research performed on animal models related to ADHD, prior to 2010. Human medical papers citing those animal studies were carefully analyzed by two independent raters to evaluate the contribution of the animal to the human studies. 211 publications describing relevant animal studies were located. Approximately half (3,342) of their 6,406 citations were by other animal studies. 446 human medical papers cited 121 of these 211 animal studies, a total of 500 times. 254 of these 446 papers were human studies of ADHD. However, only eight animal papers (cited 10 times) were relevant to the hypothesis of the human medical study in question. Three of these eight papers described results from both human and animal studies, but their citations solely referred to the human data. Five animal research papers were relevant to the hypotheses of the applicable human medical papers. Citation analysis indicates that animal research has contributed very little to contemporary understanding of ADHD. To ensure optimal allocation of Research & Development funds targeting this disease the contribution of other research methods should be similarly evaluated.

  2. Experimental Oral Candidiasis in Animal Models

    PubMed Central

    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

  3. Domestic animals as models for biomedical research.

    PubMed

    Andersson, Leif

    2016-01-01

    Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene.

  4. Domestic animals as models for biomedical research

    PubMed Central

    Andersson, Leif

    2016-01-01

    Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene. PMID:26479863

  5. Lattice animal model of chromosome organization

    NASA Astrophysics Data System (ADS)

    Iyer, Balaji V. S.; Arya, Gaurav

    2012-07-01

    Polymer models tied together by constraints of looping and confinement have been used to explain many of the observed organizational characteristics of interphase chromosomes. Here we introduce a simple lattice animal representation of interphase chromosomes that combines the features of looping and confinement constraints into a single framework. We show through Monte Carlo simulations that this model qualitatively captures both the leveling off in the spatial distance between genomic markers observed in fluorescent in situ hybridization experiments and the inverse decay in the looping probability as a function of genomic separation observed in chromosome conformation capture experiments. The model also suggests that the collapsed state of chromosomes and their segregation into territories with distinct looping activities might be a natural consequence of confinement.

  6. Animal models of glucocorticoid-induced glaucoma.

    PubMed

    Overby, Darryl R; Clark, Abbot F

    2015-12-01

    Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG.

  7. An animal model for progressive multifocal leukoencephalopathy.

    PubMed

    Haley, Sheila A; Atwood, Walter J

    2014-12-01

    JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease in humans. The disease, once considered fatal, is now managed with immune reconstitution therapy; however, surviving patients remain severely debilitated. Until now, there has been no animal model to study JCV in the brain, and research into treatment has relied on cell culture systems. In this issue of the JCI, Kondo and colleagues developed a mouse model in which human glial cells are engrafted into neonatal mice that are both immunodeficient and deficient for myelin basic protein. When challenged intracerebrally with JCV, these mice exhibit some of the characteristics of PML. The establishment of this chimeric mouse model is a significant advance toward understanding the mechanism of JCV pathogenesis and the identification of drugs to treat or prevent the disease.

  8. Animal Models of Glucocorticoid-Induced Glaucoma

    PubMed Central

    Overby, Darryl R.; Clark, Abbot F.

    2015-01-01

    Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG. PMID:26051991

  9. Animal models of premature and retarded ejaculation.

    PubMed

    Waldinger, Marcel D; Olivier, Berend

    2005-06-01

    Most of our current understanding of the neurobiology of sexual behavior and ejaculatory function has been derived from animal studies using rats with normal sexual behaviour. However, none of these proposed models adequately represents human ejaculatory disorders. Based on the "ejaculation distribution theory", which postulates that the intravaginal ejaculation latency time in men is represented by a biological continuum, we have developed an animal model for the research of premature and delayed ejaculation. In this model, a large number of male Wistar rats are investigated during 4-6 weekly sexual behavioural tests. Based on the number of ejaculations during 30 min tests, rapid and sluggish ejaculating rats are distinguished, each representing approximately 10% at both ends of a Gaussian distribution. Together with other parameters, such as ejaculation latency time, these rats at either side of the spectrum resemble men with premature and delayed ejaculation, respectively. Comparable to the human situation, in a normal population of rats, endophenotypes exist with regard to basal sexual (ejaculatory) performance.

  10. Animal models of restricted repetitive behavior in autism

    PubMed Central

    Lewis, Mark H.; Tanimura, Yoko; Lee, Linda W.; Bodfish, James W.

    2013-01-01

    Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather than attempts to model the etiology or pathophysiology of restricted, repetitive behavior, as these are poorly understood. This review focuses on our work with deer mice which exhibit repetitive behaviors associated with environmental restriction. Repetitive behaviors are the most common category of abnormal behavior observed in confined animals and larger, more complex environments substantially reduce the development and expression of such behavior. Studies with this model, including environmental enrichment effects, suggest alterations in cortical-basal ganglia circuitry in the development and expression of repetitive behavior. Considerably more work needs to be done in this area, particularly in modeling the development of aberrant repetitive behavior. As mutant mouse models continue to proliferate, there should be a number of promising genetic models to pursue. PMID:16997392

  11. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    PubMed

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E(-16)). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

  12. Modeling Protein Folding and Applying It to a Relevant Activity

    ERIC Educational Resources Information Center

    Nelson, Allan; Goetze, Jim

    2004-01-01

    The different levels of protein structure that can be easily understood by creating a model that simulates protein folding, which can then be evaluated by applying it to a relevant activity, is presented. The materials required and the procedure for constructing a protein folding model are mentioned.

  13. Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases.

    PubMed

    Kifle, Yimer Wasihun; Goeyvaerts, Nele; Van Kerckhove, Kim; Willem, Lander; Kucharski, Adam; Faes, Christel; Leirs, Herwig; Hens, Niel; Beutels, Philippe

    2015-01-01

    Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0-9 years) and adults (25-54 years) have the highest potential to cause a major zoonotic outbreak.

  14. Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases

    PubMed Central

    Kifle, Yimer Wasihun; Goeyvaerts, Nele; Van Kerckhove, Kim; Willem, Lander; Faes, Christel; Leirs, Herwig; Hens, Niel; Beutels, Philippe

    2015-01-01

    Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0–9 years) and adults (25–54 years) have the highest potential to cause a major zoonotic outbreak. PMID:26193480

  15. Animal models in the investigation of anorexia.

    PubMed

    Siegfried, Zahava; Berry, Elliot M; Hao, Shuzhen; Avraham, Yosefa

    2003-06-01

    Anorexia nervosa (AN) is an eating disorder of unknown origin that most commonly occurs in women and usually has its onset in adolescence. Patients with AN invariably have a disturbed body image and an intense fear of weight gain. There is currently no definitive treatment for this disease, which carries a 20% mortality over 20 years. Development of an appropriate animal model of AN has been difficult, as the etiology of this eating disorder likely involves a complex interaction between genetic, environmental, social, and cultural factors. In this review, we focus on several possible rodent models of AN. In our laboratory, we have developed and studied three different mouse models of AN based on clinical profiles of the disease; separation stress, activity, and diet restriction (DR). In addition, we discuss the spontaneous mouse mutation anx/anx and several mouse gene knockout models, which have resulted in an anorexic phenotype. We highlight what has been learned from each of these models and possibilities for future models. It is hoped that a combination of the study of such models, together with genetic and clinical studies in patients, will lead to more rational and successful prevention/treatment of this tragic, and often fatal, disease.

  16. [Diseases with relevance to protection of animals with an example of the musculoskeletal system of dogs].

    PubMed

    Petri, S; Distl, O; Meyer-Lindenberg, A; Nolte, I

    2000-03-01

    Protection of animals needs major concern in breeding programmes especially if inherited diseases occur which cause pain, suffering and/or damages for the animals. Dogs breeders and people keeping dogs as well as veterinarians should be informed about the etiology on sequels of diseases which cause pain to the animals and from which the animals have to be protected in order to make them more conscious on these problems and to achieve changes in dog breeding programmes. The information system "Inherited Diseases of the Musculoskeletal System of Dogs" should display the already published knowledge about etiology, pathogenesis, appearance, therapy and genetics of these diseases. This information system was built up in such a way that it can be used by students as a learning programme to understand the basic relationships among animal protection, diseases, and dog breeding. The user is also supplied with support for breeding decisions as well as for interpretation of breeding values and genotype probabilities. Additionally, information can be obtained on all in the German Association for Dog Breeding (VDH) represented breeds and breeding clubs. Actions to reduce genetically caused diseases required for members of dog breeding clubs are also available. The information system ist programmed by using HTML (Hyper Text Markup Language). Publication is possible on CD-ROM and on Internet. The supplied hyperlinks allow to make use of other publications on the world wide web related to dog and diseases of dogs.

  17. Neuropsychiatric SLE: from animal model to human.

    PubMed

    Pikman, R; Kivity, S; Levy, Y; Arango, M-T; Chapman, J; Yonath, H; Shoenfeld, Y; Gofrit, S G

    2017-04-01

    Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.

  18. Animal Models of Parkinson's Disease: Vertebrate Genetics

    PubMed Central

    Lee, Yunjong; Dawson, Valina L.; Dawson, Ted M.

    2012-01-01

    Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed. PMID:22960626

  19. Animal models of primary biliary cirrhosis.

    PubMed

    Wang, Jinjun; Yang, Guo-Xiang; Tsuneyama, Koichi; Gershwin, M Eric; Ridgway, William M; Leung, Patrick S C

    2014-08-01

    Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.

  20. Percutaneous vertebroplasty: a new animal model.

    PubMed

    Oliveira, Maria Teresa; Potes, José; Queiroga, Maria Cristina; Castro, José L; Pereira, Alfredo F; Rehman, Sarrawat; Dalgarno, Kenneth; Ramos, António; Vitale-Brovarone, Chiara; Reis, Joana C

    2016-10-01

    Percutaneous vertebroplasty (PVP) is a minimally invasive surgical procedure and is frequently performed in humans who need surgical treatment of vertebral fractures. PVP involves cement injection into the vertebral body, thereby providing rapid and significant pain relief. The testing of novel biomaterials depends on suitable animal models. The aim of this study was to develop a reproducible and safe model of PVP in sheep. This study used ex vivo and in vivo large animal model study (Merino sheep). Ex vivo vertebroplasty was performed through a bilateral modified parapedicular access in 24 ovine lumbar hemivertebrae, divided into four groups (n=6). Cerament (Bone Support, Lund, Sweden) was the control material. In the experimental group, a novel composite was tested-Spine-Ghost-which consisted of an alpha-calcium sulfate matrix enriched with micrometric particles of mesoporous bioactive glass. All vertebrae were assessed by micro-computed tomography (micro-CT) and underwent mechanical testing. For the in vivo study, 16 sheep were randomly allocated into control and experimental groups (n=8), and underwent PVP using the same bone cements. All vertebrae were assessed postmortem by micro-CT, histology, and reverse transcription-polymerase chain reaction (rt-PCR). This work has been supported by the European Commission under the 7th Framework Programme for collaborative projects (600,000-650,000 USD). In the ex vivo model, the average defect volume was 1,275.46±219.29 mm(3). Adequate defect filling with cement was observed. No mechanical failure was observed under loads which were higher than physiological. In the in vivo study, cardiorespiratory distress was observed in two animals, and one sheep presented mild neurologic deficits in the hind limbs before recovering. The model of PVP is considered suitable for preclinical in vivo studies, mimicking clinical application. All sheep recovered and completed a 6-month implantation period. There was no evidence of

  1. Animal Models of Fibrotic Lung Disease

    PubMed Central

    Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

    2013-01-01

    Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

  2. Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery.

    PubMed

    Ruggeri, Bruce A; Camp, Faye; Miknyoczki, Sheila

    2014-01-01

    Preclinical models of human cancers are indispensable in the drug discovery and development process for new cancer drugs, small molecules and biologics. They are however imperfect facsimiles of human cancers given the genetic and epigenetic heterogeneity of the latter and the multiplicity of dysregulated survival and growth-regulatory pathways that characterize this spectrum of diseases. This review discusses pre-clinical tumor models - traditional ectopic xenografts, orthotopic xenografts, genetically engineered tumor models, primary human tumorgrafts, and various multi-stage carcinogen-induced tumor models - their advantages, limitations, physiological and pathological relevance. Collectively, these animal models represent a portfolio of test systems that should be utilized at specific stages in the drug discovery process in a pragmatic and hierarchical manner of increasing complexity, physiological relevance, and clinical predictability of the human response. Additionally, evaluating the efficacy of novel therapeutic agents emerging from drug discovery programs in a variety of pre-clinical models can better mimic the heterogeneity of human cancers and also aid in establishing dose levels, dose regimens and drug combinations for use in clinical trials. Nonetheless, despite the sophistication and physiological relevance of these human cancer models (e.g., genetically engineered tumor models and primary human tumografts), the ultimate proof of concept for efficacy and safety of novel oncology therapeutics lies in humans. The judicious interpretation and extrapolation of data derived from these models to humans, and a correspondingly greater emphasis placed on translational medical research in early stage clinical trials, are essential to improve on the current clinical attrition rates for novel oncology therapeutic agents.

  3. Animating Talk and Texts: Culturally Relevant Teacher Read-Alouds of Informational Texts

    ERIC Educational Resources Information Center

    May, Laura

    2011-01-01

    This article describes the classroom interactions surrounding teacher read-alouds of nonfiction texts in the classroom of a teacher who strived for cultural relevancy. Participants in this study were one European American teacher and her upper-elementary students who lived in the surrounding working-class neighborhood; all but two students…

  4. Animal models, prophylaxis, and therapeutics for arenavirus infections.

    PubMed

    Vela, Eric

    2012-09-01

    Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection.

  5. Animal Models, Prophylaxis, and Therapeutics for Arenavirus Infections

    PubMed Central

    Vela, Eric

    2012-01-01

    Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection. PMID:23170184

  6. Biochemical correlates in an animal model of depression

    SciTech Connect

    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.

  7. Estimating the predictive validity of diabetic animal models in rosiglitazone studies.

    PubMed

    Varga, O E; Zsíros, N; Olsson, I A S

    2015-06-01

    For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals. © 2015 World Obesity.

  8. Vaccines and animal models for arboviral encephalitides.

    PubMed

    Nalca, Aysegul; Fellows, Patricia F; Whitehouse, Chris A

    2003-11-01

    Arthropod-borne viruses ("arboviruses") cause significant human illness ranging from mild, asymptomatic infection to fatal encephalitis or hemorrhagic fever. The most significant arboviruses causing human illness belong to genera in three viral families, Togaviridae, Flaviviridae, and Bunyaviridae. These viruses represent a significant public health threat to many parts of the world, and, as evidenced by the recent introduction of the West Nile virus (WNV) to the Western Hemisphere, they can no longer be considered specific to any one country or region of the world. Like most viral diseases, there are no specific therapies for the arboviral encephalitides; therefore, effective vaccines remain the front line of defense for these diseases. With this in mind, the development of new, more effective vaccines and the appropriate animal models in which to test them become paramount. In fact, for many important arboviruses (e.g. California serogroup and St. Louis encephalitis viruses), there are currently no approved vaccines available for human use. For others, such as the alphaviruses, human vaccines are available only as Investigational New Drugs, and thus are not in widespread use. On the other hand, safe and effective vaccines against tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JEV) have been in use for decades. New challenges in vaccine development have been met with new technologies in vaccine research. Many of the newer vaccines are now being developed by recombinant DNA technology. For example, chimeric virus vaccines have been developed using infectious clone technology for many of the arboviruses including, WNV, JEV, and TBEV. Other successful approaches have involved the use of naked DNA encoding and subsequently expressing the desired protective epitopes. Naked DNA vaccines have been used for TBEV and JEV and are currently under development for use against WNV. The development of less expensive, more authentic animal models to

  9. Animal and human models to understand ageing.

    PubMed

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  10. [Analysis of dalbavancin in animal models].

    PubMed

    Murillo, Óscar; El-Haj, Cristina

    2017-01-01

    Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms.

  11. Relevance Data for Language Models Using Maximum Likelihood.

    ERIC Educational Resources Information Center

    Bodoff, David; Wu, Bin; Wong, K. Y. Michael

    2003-01-01

    Presents a preliminary empirical test of a maximum likelihood approach to using relevance data for training information retrieval parameters. Discusses similarities to language models; the unification of document-oriented and query-oriented views; tests on data sets; algorithms and scalability; and the effectiveness of maximum likelihood…

  12. Models of Relevant Cue Integration in Name Retrieval

    ERIC Educational Resources Information Center

    Lombardi, Luigi; Sartori, Giuseppe

    2007-01-01

    Semantic features have different levels of importance in indexing a target concept. The article proposes that semantic relevance, an algorithmically derived measure based on concept descriptions, may efficiently capture the relative importance of different semantic features. Three models of how semantic features are integrated in terms of…

  13. Models of Relevant Cue Integration in Name Retrieval

    ERIC Educational Resources Information Center

    Lombardi, Luigi; Sartori, Giuseppe

    2007-01-01

    Semantic features have different levels of importance in indexing a target concept. The article proposes that semantic relevance, an algorithmically derived measure based on concept descriptions, may efficiently capture the relative importance of different semantic features. Three models of how semantic features are integrated in terms of…

  14. Mousepox, a small animal model of smallpox.

    PubMed

    Esteban, David; Parker, Scott; Schriewer, Jill; Hartzler, Hollyce; Buller, R Mark

    2012-01-01

    Ectromelia virus infections in the laboratory mouse have emerged as a valuable model to investigate human orthopoxvirus infections to understand the progression of disease, to discover and characterize antiviral treatments, and to study the host-pathogen relationship as it relates to pathogenesis and the immune response. Here we describe how to safely work with the virus and protocols for common procedures for the study of ectromelia virus in the laboratory mouse including the preparation of virus stocks, the use of various routes of inoculation, and collection of blood and tissue from infected animals. In addition, several procedures are described for assessing the host response to infection: for example, measurement of virus-specific CD8 T cells and the use of ELISA and neutralization assays to measure orthopoxvirus-specific antibody titers.

  15. Fetal akinesia deformation sequence: an animal model.

    PubMed

    Moessinger, A C

    1983-12-01

    Rat fetuses were paralyzed by daily transuterine injections of curare from day 18 of gestation until term (day 21). The following anomalies were noted at the time of delivery: multiple joint contractures, pulmonary hypoplasia, micrognathia, fetal growth retardation, short umbilical cords, and polyhydramnios. Neither sham-operated nor untouched littermate control fetuses had any of these anomalies. The group of anomalies (or deformation sequence) obtained with this animal model is presumed to result from the paralytic effect of curare. This phenotype bears a striking resemblance to the syndrome of ankyloses, facial anomalies, and pulmonary hypoplasia (also known as Pena and Shokeir I), presumably inherited in an autosomal recessive manner. It is suggested that this phenotype is not specific but, rather, represents a deformation sequence which results from fetal immobilization or akinesia. Diagnostic evaluation of patients with this group of anomalies should include the identification of the underlying pathologic process (etiology of the akinesia) to allow for proper classification and genetic counseling.

  16. Naphthalene animal carcinogenicity and human relevancy: overview of industries with naphthalene-containing streams.

    PubMed

    Jeffrey Lewis, R

    2012-02-01

    Bioassays in mice and rats exposed via inhalation to naphthalene show incidences of lung and nasal cancer, respectively. To address the question of human relevancy, a literature search for cancer case reports in workers exposed to naphthalene was performed, along with an evaluation of major studies from industries with naphthalene-containing streams having the highest naphthalene exposures and/or most extensive epidemiology data. Although no epidemiologic studies of workers exposed solely to naphthalene were found, a population-based case-control study of oral and oropharynx cancer found no relation with naphthalene exposure. Limited case reports of laryngeal and colorectal cancer and naphthalene exposure exist, but these data are inadequate for evaluating human cancer risk. No case reports of nasal tumors were found, which is informative because case reports have historically identified several occupational carcinogens. Combined with anatomic and metabolic differences between rodent and human upper airways and data suggesting that cancer potency based on the rat bioassay is overestimated, relevancy of rat nasal tumors to humans is questionable. For lung cancer, existing human studies are insufficient to make firm conclusions about the presence or absence of a potential naphthalene-related risk, although no occupationally-related lung cancer risks were identified in the industries evaluated. Copyright © 2011. Published by Elsevier Inc.

  17. Components of plastic: experimental studies in animals and relevance for human health

    PubMed Central

    Talsness, Chris E.; Andrade, Anderson J. M.; Kuriyama, Sergio N.; Taylor, Julia A.; vom Saal, Frederick S.

    2009-01-01

    Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds. PMID:19528057

  18. Is gastrointestinal microbiota relevant for endogenous mercury methylation in terrestrial animals?

    PubMed

    Martín-Doimeadios, R C Rodríguez; Mateo, R; Jiménez-Moreno, M

    2017-01-01

    The active role of gastrointestinal microbiota in mercury (Hg) methylation has been investigated in different terrestrial organisms from insects or annelids to rats and mammals, including the human beings. Some findings reveal the animal digestive tracts as new potential niches for Hg methylation especially in terrestrial invertebrates. However, contradictory results have been reported so far and there is still a long way to fully understand how important the MeHg production in this habitat could be, as well as its implications on the toxicity and biomagnification of MeHg within terrestrial food chains. It is important to know what has been studied in the past and discuss the previous results according to the new perspectives opened in this field. Therefore, the aim of this work is to review the present state of knowledge about the potential capability of gastrointestinal microbiota in Hg methylation with special emphasis in terrestrial animals and to propose new approaches profiting the new and powerful molecular and analytical tools.

  19. Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance.

    PubMed

    Salin, Karine; Auer, Sonya K; Rey, Benjamin; Selman, Colin; Metcalfe, Neil B

    2015-08-07

    It is often assumed that an animal's metabolic rate can be estimated through measuring the whole-organism oxygen consumption rate. However, oxygen consumption alone is unlikely to be a sufficient marker of energy metabolism in many situations. This is due to the inherent variability in the link between oxidation and phosphorylation; that is, the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this article, we describe how the P/O ratio can vary within and among individuals, and in response to a number of environmental parameters, including diet and temperature. As the P/O ratio affects the efficiency of cellular energy production, its variability may have significant consequences for animal performance, such as growth rate and reproductive output. We explore the adaptive significance of such variability and hypothesize that while a reduction in the P/O ratio is energetically costly, it may be associated with advantages in terms of somatic maintenance through reduced production of reactive oxygen species. Finally, we discuss how considering variation in mitochondrial efficiency, together with whole-organism oxygen consumption, can permit a better understanding of the relationship between energy metabolism and life history for studies in evolutionary ecology. © 2015 The Authors.

  20. Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rey, Benjamin; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    It is often assumed that an animal's metabolic rate can be estimated through measuring the whole-organism oxygen consumption rate. However, oxygen consumption alone is unlikely to be a sufficient marker of energy metabolism in many situations. This is due to the inherent variability in the link between oxidation and phosphorylation; that is, the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this article, we describe how the P/O ratio can vary within and among individuals, and in response to a number of environmental parameters, including diet and temperature. As the P/O ratio affects the efficiency of cellular energy production, its variability may have significant consequences for animal performance, such as growth rate and reproductive output. We explore the adaptive significance of such variability and hypothesize that while a reduction in the P/O ratio is energetically costly, it may be associated with advantages in terms of somatic maintenance through reduced production of reactive oxygen species. Finally, we discuss how considering variation in mitochondrial efficiency, together with whole-organism oxygen consumption, can permit a better understanding of the relationship between energy metabolism and life history for studies in evolutionary ecology. PMID:26203001

  1. Animal Models of Q Fever (Coxiella burnetii)

    PubMed Central

    Bewley, Kevin R

    2013-01-01

    Q fever, caused by the pathogen Coxiella burnetii, is an acute disease that can progress to become a serious chronic illness. The organism leads an obligate, intracellular lifecycle, during which it multiplies in the phagolytic compartments of the phagocytic cells of the immune system of its hosts. This characteristic makes study of the organism particularly difficult and is perhaps one of the reasons why, more than 70 y after its discovery, much remains unknown about the organism and its pathogenesis. A variety of animal species have been used to study both the acute and chronic forms of the disease. Although none of the models perfectly mimics the disease process in humans, each opens a window onto an important aspect of the pathology of the disease. We have learned that immunosuppression, overexpression of IL10, or physical damage to the heart muscle in mice and guinea pigs can induce disease that is similar to the chronic disease seen in humans, suggesting that this aspect of disease may eventually be fully understood. Models using species from mice to nonhuman primates have been used to evaluate and characterize vaccines to protect against the disease and may ultimately yield safer, less expensive vaccines. PMID:24326221

  2. Goats as an osteopenic animal model.

    PubMed

    Leung, K S; Siu, W S; Cheung, N M; Lui, P Y; Chow, D H; James, A; Qin, L

    2001-12-01

    A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.

  3. Large animal model of chronic pulmonary hypertension.

    PubMed

    Sato, Hitoshi; Hall, Candice M; Griffith, Grant W; Johnson, Kent F; McGillicuddy, John W; Bartlett, Robert H; Cook, Keith E

    2008-01-01

    A large animal model is needed to study artificial lung attachment in a setting simulating chronic lung disease with significant pulmonary hypertension (PH). This study sought to create a sheep model that develops significant PH within 60 days with a low rate of mortality. Sephadex beads were injected in the pulmonary circulation of sheep every other day for 60 days at doses of 0.5, 0.75, and 1 g (n = 10, 10, 7). Mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were obtained every 2 weeks. In the 0.5, 0.75, and 1-g groups, 90, 70, and 14.3% of sheep completed the study, respectively, with the remainder experiencing heart failure. By the 60th day, pulmonary vascular resistance had increased (p < 0.01) from 0.89 +/- 0.3 to 3.2 +/- 0.9 mm Hg/(L/min) and from 0.9 +/- 0.3 to 4.3 +/- 3.2 mm Hg/(L/min) in the 0.5 and 0.75-g groups, respectively. Significant right ventricular hypertrophy was observed in the 0.75-g group but not in the 0.5-g group. Data from the 1-g group were insufficient for analysis due to high mortality. Thus, the 0.5 and 0.75-g groups generate significant PH, but the 0.75-g group is a better model of chronic PH in lung disease due to the development of right ventricular hypertrophy.

  4. Clinical staging: a necessary step in the development of improved animal models of mood disturbance?

    PubMed

    Walker, Frederick Rohan; James, Morgan H; Hickie, Ian B; McGorry, Patrick D

    2014-03-01

    Recently, it has been suggested that the clinical staging approach be considered a serious alternative framework for conceptualising mood related psychopathology. The fundamental difference between clinical staging and the now dominant categorical diagnostic framework is that the entire illness trajectory becomes relevant, as opposed to simply the end-stage. The concept of disease trajectory has significant implications for animal models of psychopathology, and particularly for animal models of depression. This article will introduce and discuss the implications of the clinical staging approach for those undertaking research using animal models of mood disturbance.

  5. [Animal models of cerebral ischemia--testing therapeutic strategies in vivo].

    PubMed

    Erdô, Franciska; Hossmann, Konstantin-Alexander

    2007-09-30

    Acute cerebral ischemia is one of the leading causes of mortality and chronic disability worldwide. Animal models of focal (stroke-type) and global (cardiac arrest-type) ischemia have been established to investigate the morphological, functional and molecular consequences and to design therapeutic strategies for the improvement of ischemic injury. Despite highly beneficial effects in experimental studies, most human clinical trials were disappointing, suggesting inefficacies in the design and/or translation of animal experiments. In this review the pathophysiologically relevant specifics of ischemia models will be discussed to provide a rational basis for the proper selection of animal models for testing therapeutic strategies under experimental conditions.

  6. Animal model of Mycoplasma fermentans respiratory infection

    PubMed Central

    2013-01-01

    Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F) of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain), Mycoplasma fermentans PG 18 (type strain) or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans. PMID:23298636

  7. The maternal deprivation animal model revisited.

    PubMed

    Marco, Eva M; Llorente, Ricardo; López-Gallardo, Meritxell; Mela, Virginia; Llorente-Berzal, Álvaro; Prada, Carmen; Viveros, María-Paz

    2015-04-01

    Early life stress, in the form of MD (24h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry.

  8. Practical application of stereological methods in experimental kidney animal models.

    PubMed

    Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

    The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Adrenomedullin and Pregnancy: Perspectives from Animal Models to Humans

    PubMed Central

    Lenhart, Patricia M.; Caron, Kathleen M.

    2012-01-01

    A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With more extensive mechanistic studies and improved consistency in clinical measurements of adrenomedullin, there is great potential for the development of adrenomedullin as a clinically-relevant biomarker in pregnancy and pregnancy complications. PMID:22425034

  10. Apoptosis in the mammalian CNS: Lessons from animal models.

    PubMed

    Lossi, L; Cantile, C; Tamagno, I; Merighi, A

    2005-07-01

    It is generally assumed that about half of the neurons produced during neurogenesis die before completion of maturation of the central nervous system (CNS). Neural cell death is also relevant in aging and several neurodegenerative diseases. Among the modalities by which neurons die, apoptosis has very much attracted the interest of investigators because in this type of cell death neurons are actively responsible for their own demise by switching on a number of genes and activating a series of specific intracellular pathways. This review focuses on the cellular and molecular mechanisms of apoptosis in normal and transgenic animal models related to naturally occurring neuronal death within the CNS. We will also consider some examples of apoptotic cell death in canine neuropathologies. A thorough analysis of naturally occurring neuronal death in vivo will offer a basis for parallel and future studies involving secondary neuronal loss such as those in neurodegenerative disorders, trauma or ischaemia.

  11. Pralidoxime in carbaryl poisoning: an animal model.

    PubMed

    Mercurio-Zappala, Maria; Hack, Jason B; Salvador, Annabella; Hoffman, Robert S

    2007-02-01

    Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning. Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test. Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%. When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose.

  12. Minireview: translational animal models of human menopause: challenges and emerging opportunities.

    PubMed

    Diaz Brinton, Roberta

    2012-08-01

    Increasing importance is placed on the translational validity of animal models of human menopause to discern risk vs. benefit for prediction of outcomes after therapeutic interventions and to develop new therapeutic strategies to promote health. Basic discovery research conducted over many decades has built an extensive body of knowledge regarding reproductive senescence across mammalian species upon which to advance animal models of human menopause. Modifications to existing animal models could rapidly address translational gaps relevant to clinical issues in human menopausal health, which include the impact of 1) chronic ovarian hormone deprivation and hormone therapy, 2) clinically relevant hormone therapy regimens (cyclic vs. continuous combined), 3) clinically relevant hormone therapy formulations, and 4) windows of opportunity and optimal duration of interventions. Modifications in existing animal models to more accurately represent human menopause and clinical interventions could rapidly provide preclinical translational data to predict outcomes regarding unresolved clinical issues relevant to women's menopausal health. Development of the next generation of animal models of human menopause could leverage advances in identifying genotypic variations in estrogen and progesterone receptors to develop personalized menopausal care and to predict outcomes of interventions for protection against or vulnerability to disease. Key to the success of these models is the close coupling between the translational target and the range of predictive validity. Preclinical translational animal models of human menopause need to keep pace with changes in clinical practice. With focus on predictive validity and strategic use of advances in genetic and epigenetic science, new animal models of human menopause have the opportunity to set new directions for menopausal clinical care for women worldwide.

  13. Searching for better animal models of BPD: a perspective.

    PubMed

    Ambalavanan, Namasivayam; Morty, Rory E

    2016-11-01

    There have been many efforts to develop good animal models of bronchopulmonary dysplasia (BPD) to better understand the pathophysiology and mechanisms underlying development of BPD as well as to test potential strategies for its prevention and treatment. This Perspectives summarizes the features of common animal models of BPD and the strengths and limitations of such models. Potential optimal approaches to development of animal models are indicated, with the underlying concepts that require emphasis. Copyright © 2016 the American Physiological Society.

  14. The Terrestrial Isopod Microbiome: An All-in-One Toolbox for Animal-Microbe Interactions of Ecological Relevance.

    PubMed

    Bouchon, Didier; Zimmer, Martin; Dittmer, Jessica

    2016-01-01

    Bacterial symbionts represent essential drivers of arthropod ecology and evolution, influencing host traits such as nutrition, reproduction, immunity, and speciation. However, the majority of work on arthropod microbiota has been conducted in insects and more studies in non-model species across different ecological niches will be needed to complete our understanding of host-microbiota interactions. In this review, we present terrestrial isopod crustaceans as an emerging model organism to investigate symbiotic associations with potential relevance to ecosystem functioning. Terrestrial isopods comprise a group of crustaceans that have evolved a terrestrial lifestyle and represent keystone species in terrestrial ecosystems, contributing to the decomposition of organic matter and regulating the microbial food web. Since their nutrition is based on plant detritus, it has long been suspected that bacterial symbionts located in the digestive tissues might play an important role in host nutrition via the provisioning of digestive enzymes, thereby enabling the utilization of recalcitrant food compounds (e.g., cellulose or lignins). If this were the case, then (i) the acquisition of these bacteria might have been an important evolutionary prerequisite for the colonization of land by isopods, and (ii) these bacterial symbionts would directly mediate the role of their hosts in ecosystem functioning. Several bacterial symbionts have indeed been discovered in the midgut caeca of terrestrial isopods and some of them might be specific to this group of animals (i.e., Candidatus Hepatoplasma crinochetorum, Candidatus Hepatincola porcellionum, and Rhabdochlamydia porcellionis), while others are well-known intracellular pathogens (Rickettsiella spp.) or reproductive parasites (Wolbachia sp.). Moreover, a recent investigation of the microbiota in Armadillidium vulgare has revealed that this species harbors a highly diverse bacterial community which varies between host populations

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

    PubMed

    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.

  16. Animal models to study gluten sensitivity.

    PubMed

    Marietta, Eric V; Murray, Joseph A

    2012-07-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70-80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.

  17. Animal Models to Study Gluten Sensitivity1

    PubMed Central

    Marietta, Eric V.; Murray, Joseph A.

    2012-01-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease. PMID:22572887

  18. RADAR realistic animal model series for dose assessment.

    PubMed

    Keenan, Mary A; Stabin, Michael G; Segars, William P; Fernald, Michael J

    2010-03-01

    Rodent species are widely used in the testing and approval of new radiopharmaceuticals, necessitating murine phantom models. As more therapy applications are being tested in animal models, calculating accurate dose estimates for the animals themselves becomes important to explain and control potential radiation toxicity or treatment efficacy. Historically, stylized and mathematically based models have been used for establishing doses to small animals. Recently, a series of anatomically realistic human phantoms was developed using body models based on nonuniform rational B-spline. Realistic digital mouse whole-body (MOBY) and rat whole-body (ROBY) phantoms were developed on the basis of the same NURBS technology and were used in this study to facilitate dose calculations in various species of rodents. Voxel-based versions of scaled MOBY and ROBY models were used with the Vanderbilt multinode computing network (Advanced Computing Center for Research and Education), using geometry and tracking radiation transport codes to calculate specific absorbed fractions (SAFs) with internal photon and electron sources. Photon and electron SAFs were then calculated for relevant organs in all models. The SAF results were compared with values from similar studies found in reference literature. Also, the SAFs were used with standardized decay data to develop dose factors to be used in radiation dose calculations. Representative plots were made of photon electron SAFs, evaluating the traditional assumption that all electron energy is absorbed in the source organs. The organ masses in the MOBY and ROBY models are in reasonable agreement with models presented by other investigators noting that considerable variation can occur between reported masses. Results consistent with those found by other investigators show that absorbed fractions for electrons for organ self-irradiation were significantly less than 1.0 at energies above 0.5 MeV, as expected for many of these small-sized organs

  19. Frontiers of model animals for neuroscience: two prosperous aging model animals for promoting neuroscience research.

    PubMed

    Ito, Koichi

    2013-01-01

    A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer's disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer's disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future.

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

    USGS Publications Warehouse

    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

  1. Animal models to evaluate anti-atherosclerotic drugs.

    PubMed

    Priyadharsini, Raman P

    2015-08-01

    Atherosclerosis is a multifactorial condition characterized by endothelial injury, fatty streak deposition, and stiffening of the blood vessels. The pathogenesis is complex and mediated by adhesion molecules, inflammatory cells, and smooth muscle cells. Statins have been the major drugs in treating hypercholesterolemia for the past two decades despite little efficacy. There is an urgent need for new drugs that can replace statins or combined with statins. The preclinical studies evaluating atherosclerosis require an ideal animal model which resembles the disease condition, but there is no single animal model which mimics the disease. The animal models used are rabbits, rats, mice, hamsters, mini pigs, etc. Each animal model has its own advantages and disadvantages. The method of induction of atherosclerosis includes diet, chemical induction, mechanically induced injuries, and genetically manipulated animal models. This review mainly focuses on the various animal models, method of induction, the advantages, disadvantages, and the current perspectives with regard to preclinical studies on atherosclerosis.

  2. [Establishment and evaluation of animal model with methamphetamine poisoning].

    PubMed

    Xu, Jing; Zhou, Xiao-Li; Zhang, Hao; Deng, Chong; Zhang, Yan; Li, Zhen

    2009-08-01

    Amphetamine-type stimulants (ATS) is the most widespread narcotics in the 21st century. The methamphetamine's intoxication mechanism, psychological dependence, drug resistance and therapeutic drug development are the hot spots in current research. Establishment of animal model with methamphetamine poisoning is the basic for the relative studies, the normalization and standardization of the animal model settles the foundation for methamphetamine's further research. This article reviews the animal model of methamphetamine poisoning in China and abroad, the brief history of the acute, subacute and chronic animal model of methamphetamine poisoning, as well as the principles and methods of the animal model establishment and its evaluation criteria. The necessity, significance and its scientific expansion of performing experimental research on the methamphetamine poisoning animal model are also discussed.

  3. Japanese monkeys (Macaca fuscata) quickly detect snakes but not spiders: Evolutionary origins of fear-relevant animals.

    PubMed

    Kawai, Nobuyuki; Koda, Hiroki

    2016-08-01

    Humans quickly detect the presence of evolutionary threats through visual perception. Many theorists have considered humans to be predisposed to respond to both snakes and spiders as evolutionarily fear-relevant stimuli. Evidence supports that human adults, children, and snake-naive monkeys all detect pictures of snakes among pictures of flowers more quickly than vice versa, but recent neurophysiological and behavioral studies suggest that spiders may, in fact, be processed similarly to nonthreat animals. The evidence of quick detection and rapid fear learning by primates is limited to snakes, and no such evidence exists for spiders, suggesting qualitative differences between fear of snakes and fear of spiders. Here, we show that snake-naive Japanese monkeys detect a single snake picture among 8 nonthreat animal pictures (koala) more quickly than vice versa; however, no such difference in detection was observed between spiders and pleasant animals. These robust differences between snakes and spiders are the most convincing evidence that the primate visual system is predisposed to pay attention to snakes but not spiders. These findings suggest that attentional bias toward snakes has an evolutionary basis but that bias toward spiders is more due to top-down, conceptually driven effects of emotion on attention capture. (PsycINFO Database Record

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

    PubMed

    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.

  5. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    PubMed

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders.

  6. Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models.

    PubMed

    Gremonprez, Félix; Willaert, Wouter; Ceelen, Wim

    2014-02-01

    The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters.

  7. Cumulative permanent environmental effects for repeated records animal models.

    PubMed

    Schaeffer, L R

    2011-04-01

    The assumption of a single permanent environmental (PE) effect contributing to every record made by an animal is questioned. An alternative model where new PE effects accumulate with each record made by an animal is proposed. An example is used to illustrate the differences between the traditional model and the proposed model.

  8. Animal models of leukemia: any closer to the real thing?

    PubMed

    Cook, Guerry J; Pardee, Timothy S

    2013-06-01

    Animal models have been invaluable in the efforts to better understand and ultimately treat patients suffering from leukemia. While important insights have been gleaned from these models, limitations must be acknowledged. In this review, we will highlight the various animal models of leukemia and describe their contributions to the improved understanding and treatment of these cancers.

  9. Animal Models of Leukemia: Any closer to the real thing?

    PubMed Central

    Cook, Guerry J; Pardee, Timothy S.

    2012-01-01

    Animal models have been invaluable in the efforts to better understand and ultimately treat patients suffering from leukemia. While important insights have been gleaned from these models, limitations must be acknowledged. In this review, we will highlight the various animal models of leukemia and describe their contributions to the improved understanding and treatment of these cancers. PMID:23081702

  10. Asymmetry of brain and behavior in animals: Its development, function, and human relevance.

    PubMed

    Rogers, Lesley J

    2014-06-01

    Since the discovery of brain asymmetry in a wide range of vertebrate species, it has become possible to study development and expression of lateralized behavior accurately in well-controlled experiments. Several species have emerged as useful models for investigating aspects of lateralization. Discussed here are: (1) the influence of exposure to light during embryonic development on lateralization, (2) effects of steroid hormones on lateralization, (3) developmental changes in which hemisphere is controlling behavior, and (4) asymmetry in memory formation and recall. The findings have bearing on understanding the development of hemispheric specialization in humans and are likely to provide insight into dysfunctional behavior associated with weak or absent lateralization and impaired interhemispheric communication (e.g., autism, schizophrenia, and dyslexia). This review features research on chicks, pigeons, and zebrafish, with the addition of some recent evidence of lateralization in bees. Discoveries made using these species have highlighted the interaction between experience, hormones, and genetic factors during development, and have provided some of the first clear evidence of the advantage of having a lateralized brain.

  11. Modeling the Encephalopathy of Prematurity in Animals: The Important Role of Translational Research

    PubMed Central

    Kinney, Hannah C.; Volpe, Joseph J.

    2012-01-01

    Translational research in preterm brain injury depends upon the delineation of the human neuropathology in order that animal models faithfully reiterate it, thereby ensuring direct relevance to the human condition. The major substrate of human preterm brain injury is the encephalopathy of prematurity that is characterized by gray and white matter lesions reflecting combined acquired insults, altered developmental trajectories, and reparative phenomena. Here we highlight the key features of human preterm brain development and the encephalopathy of prematurity that are critical for modeling in animals. The complete mimicry of the complex human neuropathology is difficult in animal models. Many models focus upon mechanisms related to a specific feature, for example, loss of premyelinating oligodendrocytes in the cerebral white matter. Nevertheless, animal models that simultaneously address oligodendrocyte, neuronal, and axonal injury carry the potential to decipher shared mechanisms and synergistic treatments to ameliorate the global consequences of the encephalopathy of prematurity. PMID:22685653

  12. A multiple relevance feedback strategy with positive and negative models.

    PubMed

    Ma, Yunlong; Lin, Hongfei

    2014-01-01

    A commonly used strategy to improve search accuracy is through feedback techniques. Most existing work on feedback relies on positive information, and has been extensively studied in information retrieval. However, when a query topic is difficult and the results from the first-pass retrieval are very poor, it is impossible to extract enough useful terms from a few positive documents. Therefore, the positive feedback strategy is incapable to improve retrieval in this situation. Contrarily, there is a relatively large number of negative documents in the top of the result list, and it has been confirmed that negative feedback strategy is an important and useful way for adapting this scenario by several recent studies. In this paper, we consider a scenario when the search results are so poor that there are at most three relevant documents in the top twenty documents. Then, we conduct a novel study of multiple strategies for relevance feedback using both positive and negative examples from the first-pass retrieval to improve retrieval accuracy for such difficult queries. Experimental results on these TREC collections show that the proposed language model based multiple model feedback method which is generally more effective than both the baseline method and the methods using only positive or negative model.

  13. Chemical kinetic modeling of component mixtures relevant to gasoline

    SciTech Connect

    Mehl, M; Curran, H J; Pitz, W J; Dooley, S; Westbrook, C K

    2008-05-29

    Detailed kinetic models of pyrolysis and combustion of hydrocarbon fuels are nowadays widely used in the design of internal combustion engines and these models are effectively applied to help meet the increasingly stringent environmental and energetic standards. In previous studies by the combustion community, such models not only contributed to the understanding of pure component combustion, but also provided a deeper insight into the combustion behavior of complex mixtures. One of the major challenges in this field is now the definition and the development of appropriate surrogate models able to mimic the actual features of real fuels. Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. Their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. Aside the most commonly used surrogates containing iso-octane and n-heptane only, the so called Primary Reference Fuels (PRF), new mixtures have recently been suggested to extend the reference components in surrogate mixtures to also include alkenes and aromatics. It is generally agreed that, including representative species for all the main classes of hydrocarbons which can be found in real fuels, it is possible to reproduce very effectively in a wide range of operating conditions not just the auto-ignition propensity of gasoline or Diesel fuels, but also their physical properties and their combustion residuals [1]. In this work, the combustion behavior of several components relevant to gasoline surrogate formulation is computationally examined. The attention is focused on the autoignition of iso-octane, hexene and their mixtures. Some important issues relevant to the experimental and modeling investigation of such fuels are discussed with the help of rapid compression machine data and calculations. Following the model validation, the behavior of mixtures is discussed on the

  14. ANIMAL MODELS OF CHRONIC PESTICIDE NEUROTOXICITY.

    EPA Science Inventory

    There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few studies of- long-term exposure. Many reports in the literature describing ;chronic' exposures to pesticides are, in fa...

  15. ANIMAL MODELS OF CHRONIC PESTICIDE NEUROTOXICITY.

    EPA Science Inventory

    There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few reports of long-term exposure. Reports in the literature describing "chronic" exposures to pesticides are, in fact, a...

  16. ANIMAL MODELS OF CHRONIC PESTICIDE NEUROTOXICITY.

    EPA Science Inventory

    There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few studies of- long-term exposure. Many reports in the literature describing ;chronic' exposures to pesticides are, in fa...

  17. ANIMAL BEHAVIOR AND WELL-BEING SYMPOSIUM: Interaction between coping style/personality, stress, and welfare: Relevance for domestic farm animals.

    PubMed

    Koolhaas, J M; Van Reenen, C G

    2016-06-01

    This paper will argue that understanding animal welfare and the individual vulnerability to stress-related disease requires a fundamental understanding of functional individual variation as it occurs in nature as well as the underlying neurobiology and neuroendocrinology. Ecological studies in feral populations of mice, fish, and birds start to recognize the functional significance of phenotypes that individually differ in their behavioral and neuroendocrine response to environmental challenge. Recent studies indicate that the individual variation within a species may buffer the species for strong fluctuations in the natural habitat. Similarly, evolutionary ancient behavioral trait characteristics have now been identified in a range of domestic farm animals including cattle, pigs, and horses. Individual variation in behavior can be summarized in a 3-dimensional model with coping style, emotionality, and sociality as independent dimensions. These dimensions can be considered trait characteristics that are stable over time and across situations within the individual. This conceptual model has several consequences. First, the coping style dimension is strongly associated with differential stress vulnerability. Social stress studies show that proactive individuals are resilient under stable environmental conditions but vulnerable when outcome expectancies are violated. Reactive individuals are, in fact, rather flexible and seem to adapt more easily to a changing environment. A second consequence relates to genetics and breeding. Genetic selection for one trait usually implies selection for other traits as well. It is discussed that a more balanced breeding program that takes into account biologically functional temperamental traits will lead to more robust domestic farm animals. Finally, the relationship between temperamental traits, animal production, fitness, and welfare is discussed.

  18. Institutional Animal Care and Use Committee Considerations for Animal Models of Peripheral Neuropathy

    PubMed Central

    Brabb, Thea; Carbone, Larry; Snyder, Jessica; Phillips, Nona

    2014-01-01

    Peripheral neuropathy and neuropathic pain are debilitating, life-altering conditions that affect a significant proportion of the human population. Animal models, used to study basic disease mechanisms and treatment modalities, are diverse and provide many challenges for institutional animal care and use committee (IACUC) review and postapproval monitoring. Items to consider include regulatory and ethical imperatives in animal models that may be designed to study pain, the basic mechanism of neurodegeneration, and different disease processes for which neuropathic pain is a side effect. Neuropathic pain can be difficult to detect or quantify in many models, and pain management is often unsuccessful in both humans and animals, inspiring the need for more research. Design of humane endpoints requires clear communication of potential adverse outcomes and solutions. Communication with the IACUC, researchers, and veterinary staff is also key for successful postapproval monitoring of these challenging models. PMID:24615447

  19. Institutional animal care and use committee considerations for animal models of peripheral neuropathy.

    PubMed

    Brabb, Thea; Carbone, Larry; Snyder, Jessica; Phillips, Nona

    2014-01-01

    Peripheral neuropathy and neuropathic pain are debilitating, life-altering conditions that affect a significant proportion of the human population. Animal models, used to study basic disease mechanisms and treatment modalities, are diverse and provide many challenges for institutional animal care and use committee (IACUC) review and postapproval monitoring. Items to consider include regulatory and ethical imperatives in animal models that may be designed to study pain, the basic mechanism of neurodegeneration, and different disease processes for which neuropathic pain is a side effect. Neuropathic pain can be difficult to detect or quantify in many models, and pain management is often unsuccessful in both humans and animals, inspiring the need for more research. Design of humane endpoints requires clear communication of potential adverse outcomes and solutions. Communication with the IACUC, researchers, and veterinary staff is also key for successful postapproval monitoring of these challenging models.

  20. Bursting processes in plasmas and relevant nonlinear model equations

    SciTech Connect

    Basu, B.; Coppi, B.

    1995-01-01

    Important intrinsic plasma instabilities manifest themselves in the form of periodic bursts of fluctuations rather than as a state of stationary fluctuations, which a conventional application of quasilinear theory would lead to expect. A set of coupled nonlinear equations for the time evolution of the fluctuation amplitude and of the driving factor of the relevant instability is shown to have the features necessary to reproduce the variety of bursts that are observed experimentally. These are the periodicity, the duration, and the shape of the bursts, special consideration being given to the excitation of modes by high-energy particle populations in thermalized plasmas and to a model for the transition from a bursting state to one of stationary fluctuations. A model is introduced that is relevant to the case where the spatial dependence of the mode amplitude is important. The application of the given analysis to the bursty wave emissions observed in space is discussed. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  1. Validating animal models for preclinical research: a scientific and ethical discussion.

    PubMed

    Varga, Orsolya E; Hansen, Axel K; Sandøe, Peter; Olsson, I Anna S

    2010-06-01

    The use of animals to model humans in biomedical research relies on the notion that basic processes are sufficiently similar across species to allow extrapolation. Animal model validity is discussed in terms of the similarity between the model and the human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with the use of non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. We discuss both the potential and the limitations of validating preclinical animal models for proof-of-concept studies, by using an approach similar to that applied to alternative non-animal methods in toxicology and safety testing. A major challenge in devising a validation system for animal models is the lack of a clear gold standard with which to compare results. While a complete adoption of the validation approach for alternative methods is probably inappropriate for research animal models, key features, such as making data available for external validation and defining a strategy to run experiments in a way that permits meaningful retrospective analysis, remain highly relevant.

  2. Chemical kinetic modeling of component mixtures relevant to gasoline

    SciTech Connect

    Mehl, M; Curran, H J; Pitz, W J; Westbrook, C K

    2009-02-13

    Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. It is generally agreed that their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. In this work, a recently revised version of the kinetic model by the authors is used to analyze the combustion behavior of several components relevant to gasoline surrogate formulation. Particular attention is devoted to linear and branched saturated hydrocarbons (PRF mixtures), olefins (1-hexene) and aromatics (toluene). Model predictions for pure components, binary mixtures and multi-component gasoline surrogates are compared with recent experimental information collected in rapid compression machine, shock tube and jet stirred reactors covering a wide range of conditions pertinent to internal combustion engines. Simulation results are discussed focusing attention on the mixing effects of the fuel components.

  3. Hierarchical animal movement models for population-level inference

    USGS Publications Warehouse

    Hooten, Mevin B.; Buderman, Frances E.; Brost, Brian M.; Hanks, Ephraim M.; Ivans, Jacob S.

    2016-01-01

    New methods for modeling animal movement based on telemetry data are developed regularly. With advances in telemetry capabilities, animal movement models are becoming increasingly sophisticated. Despite a need for population-level inference, animal movement models are still predominantly developed for individual-level inference. Most efforts to upscale the inference to the population level are either post hoc or complicated enough that only the developer can implement the model. Hierarchical Bayesian models provide an ideal platform for the development of population-level animal movement models but can be challenging to fit due to computational limitations or extensive tuning required. We propose a two-stage procedure for fitting hierarchical animal movement models to telemetry data. The two-stage approach is statistically rigorous and allows one to fit individual-level movement models separately, then resample them using a secondary MCMC algorithm. The primary advantages of the two-stage approach are that the first stage is easily parallelizable and the second stage is completely unsupervised, allowing for an automated fitting procedure in many cases. We demonstrate the two-stage procedure with two applications of animal movement models. The first application involves a spatial point process approach to modeling telemetry data, and the second involves a more complicated continuous-time discrete-space animal movement model. We fit these models to simulated data and real telemetry data arising from a population of monitored Canada lynx in Colorado, USA.

  4. Animal models in the research of abdominal aortic aneurysms development.

    PubMed

    Patelis, N; Moris, D; Schizas, D; Damaskos, C; Perrea, D; Bakoyiannis, C; Liakakos, T; Georgopoulos, S

    2017-09-22

    Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms "animal" or ''animal model(s)'' and keywords "research", ''aneurysm(s)'', "aorta", ''pancreatic elastase'', "Angiotensin", "AngII" "Calcium Chloride" or "CaCl(2)". Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty A. and Cassis L.A. We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960's. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are inline with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.

  5. Awareness, perceived relevance, and acceptance of large animal hospital surveillance and infection control practices by referring veterinarians and clients.

    PubMed

    Ekiri, Abel B; House, Amanda M; Krueger, Traci M; Hernandez, Jorge A

    2014-04-01

    To assess awareness, perceived relevance, and acceptance of surveillance and infection control practices at a large animal referral hospital among referring veterinarians and clients who sent horses to the facility for veterinary care. Survey. 57 referring veterinarians and 594 clients. A 15-question survey targeting Salmonella enterica as an important pathogen of interest in horses was sent to clients who sent ≥ 1 horse to the University of Florida Large Animal Hospital for veterinary care during July 1, 2007, through July 1, 2011, and to veterinarians who had referred horses to the same hospital prior to July 1, 2011. Responses were summarized with descriptive statistics. The χ(2) test and the Wilcoxon rank sum test were used to examine associations among variables of interest. Survey response rates were low (57/467 [12%] for veterinarians and 594/3,095 [19%] for clients). Significantly more (35/56 [63%]) veterinarians than clients (227/585 [39%]) were aware that the hospital operates a surveillance and infection control program. Most veterinarians (56/57 [98%]) and clients (554/574 [97%]) indicated that sampling and testing of horses to detect Salmonella shedding in feces at admission and during hospitalization was justified. In addition, on a scale of 1 (not important) to 10 (very important), veterinarians and clients indicated it was very important (median score, 10 [interquartile range, 8 to 10] for both groups) that a referral hospital operates a surveillance and infection control program. Survey results indicated that awareness of hospital surveillance and infection control practices was higher among veterinarians than clients, and these practices were considered relevant and well-accepted among participant veterinarians and clients.

  6. Of mice and men (and women and children): scientific and ethical implications of animal models.

    PubMed

    Bird, S J; Parlee, M B

    2000-11-01

    1. Animal models of human behavior and disease are commonly used and have contributed significantly to progress in understanding the physiological mechanisms of both normal function and disease, and in the development of effective therapies. 2. Little attention has been given, however, to the scientific and ethical implications of choosing a particular animal model. 3. This paper discusses the rationale for the selection of particular animal models that have been chosen to study certain human diseases or behaviors, and provides examples to illustrate how underlying assumptions about methods and about physiological mechanisms and other relevant features of the disease or behavior of interest are embedded in the choice of an animal model. 4. Although these assumptions influence the direction of research, they are rarely analyzed explicitly, or evaluated empirically. The authors recommend that assumptions should be clearly stated and that, whenever possible, they be specifically and thoroughly evaluated empirically.

  7. Rapporteur report: cellular, animal and epidemiological studies of the effects of static magnetic fields relevant to human health.

    PubMed

    Leszczynski, Dariusz

    2005-01-01

    Three talks were presented in the session on "Cellular, Animal and Epidemiological Studies of the Effects of Static Magnetic Fields Relevant to Human Health". The first talk presented the in vitro effects of static magnetic fields on cell cultures. The second talk presented the in vivo evidence obtained from animal studies. The final, third talk, presented the evidence obtained from epidemiological studies. The overall conclusion of the three presentations and the following general discussion was that the scientific evidence available to date is weak and contains large gaps in knowledge either due to the poor quality of published studies or because of the lack of published research on certain health-related topics. It was emphasized that the rapid development of new technological applications of static magnetic fields (e.g. magnetic levitation trains or magnetic resonance imaging-MRI) results in the human population at large, in certain occupations, and in a selected population of clinical patients being exposed to ever increasing static magnetic field strengths. It is of concern that the knowledge presently available concerning the health effects of these strong static magnetic fields is lagging a long way behind technological development. In conclusion, it was suggested that there is an urgent need to perform new studies in all research areas (in vitro, in vivo and epidemiology) in order to fill the present gaps in knowledge and provide assurance that this technology will not cause any unwanted and unexpected health side effects.

  8. Are animal models as good as we think?

    USDA-ARS?s Scientific Manuscript database

    Models have been a tool of science at least since the 18th century and serve a variety of purposes from focusing abstract thoughts to representing scaled down version of things for study. Generally, animal models are needed when it is impractical or unethical to study the target animal. Biologists...

  9. The Various Roles of Animal Models in Understanding Human Development

    ERIC Educational Resources Information Center

    Gottlieb, Gilbert; Lickliter, Robert

    2004-01-01

    In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…

  10. Overview of Vertebrate Animal Models of Fungal Infection

    PubMed Central

    Hohl, Tobias M.

    2014-01-01

    Fungi represent emerging infectious threats to human populations worldwide. Mice and other laboratory animals have proved invaluable in modeling clinical syndromes associated with superficial and life-threatening invasive mycoses. This review outlines salient features of common vertebrate animal model systems to study fungal pathogenesis, host antifungal immune responses, and antifungal compounds. PMID:24709390

  11. The Various Roles of Animal Models in Understanding Human Development

    ERIC Educational Resources Information Center

    Gottlieb, Gilbert; Lickliter, Robert

    2004-01-01

    In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…

  12. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For

  13. Formal models in animal-metacognition research: the problem of interpreting animals' behavior.

    PubMed

    Smith, J David; Zakrzewski, Alexandria C; Church, Barbara A

    2016-10-01

    Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly.

  14. Animal models of human respiratory syncytial virus disease

    PubMed Central

    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 novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research. PMID:21571908

  15. Animal models of human respiratory syncytial virus disease.

    PubMed

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

    2011-08-01

    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 novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research.

  16. Small animal models of kidney disease: a review.

    PubMed

    Hewitson, Tim D; Ono, Takahiko; Becker, Gavin J

    2009-01-01

    Animal models of renal disease have provided valuable insights into the pathogenesis of acute and chronic kidney disease. Extension of these models to the mouse has become an increasingly important with the development of gene knockout and transgenic animals. In this review we discuss a range of models that can be used to mimic the mechanisms of human renal disease. While not perfect, the careful and ethical use of these models offers the opportunity to examine individual mechanisms in an accelerated time frame.

  17. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    PubMed Central

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  18. Animal models for microbicide safety and efficacy testing.

    PubMed

    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.

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

    PubMed

    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.

  20. Animal Models of Tourette Syndrome-From Proliferation to Standardization.

    PubMed

    Yael, Dorin; Israelashvili, Michal; Bar-Gad, Izhar

    2016-01-01

    Tourette syndrome (TS) is a childhood onset disorder characterized by motor and vocal tics and associated with multiple comorbid symptoms. Over the last decade, the accumulation of findings from TS patients and the emergence of new technologies have led to the development of novel animal models with high construct validity. In addition, animal models which were previously associated with other disorders were recently attributed to TS. The proliferation of TS animal models has accelerated TS research and provided a better understanding of the mechanism underlying the disorder. This newfound success generates novel challenges, since the conclusions that can be drawn from TS animal model studies are constrained by the considerable variation across models. Typically, each animal model examines a specific subset of deficits and centers on one field of research (physiology/genetics/pharmacology/etc.). Moreover, different studies do not use a standard lexicon to characterize different properties of the model. These factors hinder the evaluation of individual model validity as well as the comparison across models, leading to a formation of a fuzzy, segregated landscape of TS pathophysiology. Here, we call for a standardization process in the study of TS animal models as the next logical step. We believe that a generation of standard examination criteria will improve the utility of these models and enable their consolidation into a general framework. This should lead to a better understanding of these models and their relationship to TS, thereby improving the research of the mechanism underlying this disorder and aiding the development of new treatments.

  1. Animal Models of Tourette Syndrome—From Proliferation to Standardization

    PubMed Central

    Yael, Dorin; Israelashvili, Michal; Bar-Gad, Izhar

    2016-01-01

    Tourette syndrome (TS) is a childhood onset disorder characterized by motor and vocal tics and associated with multiple comorbid symptoms. Over the last decade, the accumulation of findings from TS patients and the emergence of new technologies have led to the development of novel animal models with high construct validity. In addition, animal models which were previously associated with other disorders were recently attributed to TS. The proliferation of TS animal models has accelerated TS research and provided a better understanding of the mechanism underlying the disorder. This newfound success generates novel challenges, since the conclusions that can be drawn from TS animal model studies are constrained by the considerable variation across models. Typically, each animal model examines a specific subset of deficits and centers on one field of research (physiology/genetics/pharmacology/etc.). Moreover, different studies do not use a standard lexicon to characterize different properties of the model. These factors hinder the evaluation of individual model validity as well as the comparison across models, leading to a formation of a fuzzy, segregated landscape of TS pathophysiology. Here, we call for a standardization process in the study of TS animal models as the next logical step. We believe that a generation of standard examination criteria will improve the utility of these models and enable their consolidation into a general framework. This should lead to a better understanding of these models and their relationship to TS, thereby improving the research of the mechanism underlying this disorder and aiding the development of new treatments. PMID:27065791

  2. Animal Models for Salmonellosis: Applications in Vaccine Research.

    PubMed

    Higginson, Ellen E; Simon, Raphael; Tennant, Sharon M

    2016-09-01

    Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.

  3. Animal Models for Salmonellosis: Applications in Vaccine Research

    PubMed Central

    Higginson, Ellen E.; Simon, Raphael

    2016-01-01

    Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development. PMID:27413068

  4. Animal models of obsessive compulsive disorder: recent findings and future directions.

    PubMed

    Hoffman, Kurt Leroy

    2011-07-01

    Obsessive compulsive disorder (OCD) is a debilitating condition with limited treatment options. OCD is heterogeneous with respect to the content of obsessions and compulsions and their underlying motivation, among other characteristics. Animal models have provided important insights into the pathophysiology of OCD. The phenomenology of OCD is discussed, with emphasis on clinically-relevant subgroups. The paper also discusses the advantages and limitations of animals as models of OCD, along with considerations on assessing their validity. A PubMed database search using the terms 'animal model' and 'obsessive compulsive disorder' revealed ongoing studies in several models, including stereotypy in the deer mouse, quinpirole-induced checking, spontaneous alternation, compulsive lever pressing, genetic models, pathogenic models and models involving normal compulsive-like behavioral patterns. These models are presented with respect to their similarity to specific features of OCD and the information gained from them. Studies in many of these models point to the participation of corticostriatal thalamocortical circuitry and corticostriatal glutamate neurotransmission in the pathophysiology of compulsive-like behavior. The use of animal models takes us beyond simple serotonin- or dopamine-based models of OCD that are founded on the often limited, and still unexplained, response of OCD symptoms to serotonin reuptake inhibitors or antipsychotic therapy. Pharmacological challenges that selectively target neurochemical systems that modulate either corticostriatal glutamate or striatal dopamine neurotransmission, or indeed both, should be investigated in animal models of compulsive-like behavior. Such systems include metabotropic glutamate, adenosine and endocannabinoid receptors, among others.

  5. Animal Models Used to Explore Abdominal Aortic Aneurysms: A Systematic Review.

    PubMed

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

    2016-10-01

    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. 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. The most common models in rodents, including elastase, calcium chloride, angiotensin II, xenograft, and transgenic models, and the most common models in non-rodents, including chemically induced, graft models, and patch models, all have limitations with regard to the pathological interpretation of human AAA. Although findings from animal models of AAAs cannot be directly translated to human AAAs, the identification and awareness of animal models of AAA will provide knowledge for further investigation and insight into human AAA disease. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Systematic Reviews of Animal Models: Methodology versus Epistemology

    PubMed Central

    Greek, Ray; Menache, Andre

    2013-01-01

    Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions. PMID:23372426

  7. Systematic reviews of animal models: methodology versus epistemology.

    PubMed

    Greek, Ray; Menache, Andre

    2013-01-01

    Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.

  8. Fractional Moment Bounds and Disorder Relevance for Pinning Models

    NASA Astrophysics Data System (ADS)

    Derrida, Bernard; Giacomin, Giambattista; Lacoin, Hubert; Toninelli, Fabio Lucio

    2009-05-01

    We study the critical point of directed pinning/wetting models with quenched disorder. The distribution K(·) of the location of the first contact of the (free) polymer with the defect line is assumed to be of the form K( n) = n - α-1 L( n), with α ≥ 0 and L(·) slowly varying. The model undergoes a (de)-localization phase transition: the free energy (per unit length) is zero in the delocalized phase and positive in the localized phase. For α < 1/2 disorder is irrelevant: quenched and annealed critical points coincide for small disorder, as well as quenched and annealed critical exponents [3,28]. The same has been proven also for α = 1/2, but under the assumption that L(·) diverges sufficiently fast at infinity, a hypothesis that is not satisfied in the (1 + 1)-dimensional wetting model considered in [12,17], where L(·) is asymptotically constant. Here we prove that, if 1/2 < α < 1 or α > 1, then quenched and annealed critical points differ whenever disorder is present, and we give the scaling form of their difference for small disorder. In agreement with the so-called Harris criterion, disorder is therefore relevant in this case. In the marginal case α = 1/2, under the assumption that L(·) vanishes sufficiently fast at infinity, we prove that the difference between quenched and annealed critical points, which is smaller than any power of the disorder strength, is positive: disorder is marginally relevant. Again, the case considered in [12,17] is out of our analysis and remains open. The results are achieved by setting the parameters of the model so that the annealed system is localized, but close to criticality, and by first considering a quenched system of size that does not exceed the correlation length of the annealed model. In such a regime we can show that the expectation of the partition function raised to a suitably chosen power {γ in (0, 1)} is small. We then exploit such an information to prove that the expectation of the same fractional

  9. A Statistical Quality Model for Data-Driven Speech Animation.

    PubMed

    Ma, Xiaohan; Deng, Zhigang

    2012-11-01

    In recent years, data-driven speech animation approaches have achieved significant successes in terms of animation quality. However, how to automatically evaluate the realism of novel synthesized speech animations has been an important yet unsolved research problem. In this paper, we propose a novel statistical model (called SAQP) to automatically predict the quality of on-the-fly synthesized speech animations by various data-driven techniques. Its essential idea is to construct a phoneme-based, Speech Animation Trajectory Fitting (SATF) metric to describe speech animation synthesis errors and then build a statistical regression model to learn the association between the obtained SATF metric and the objective speech animation synthesis quality. Through delicately designed user studies, we evaluate the effectiveness and robustness of the proposed SAQP model. To the best of our knowledge, this work is the first-of-its-kind, quantitative quality model for data-driven speech animation. We believe it is the important first step to remove a critical technical barrier for applying data-driven speech animation techniques to numerous online or interactive talking avatar applications.

  10. Animal Models of Hemophilia and Related Bleeding Disorders

    PubMed Central

    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

  11. The use of animal models in diabetes research

    PubMed Central

    King, Aileen JF

    2012-01-01

    Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients. LINKED ARTICLES Animal Models This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers. Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research. Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting. Giacomotto J and Ségalat L (2010). High-throughput screening and small animal models, where are we? McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). The ARRIVE guidelines. Emerson M (2010). Refinement, reduction and replacement approaches to in vivo cardiovascular research. Berge O-G (2011). Predictive validity of behavioural animal models for chronic pain. Vickers SP, Jackson HC and Cheetham SC (2011). The utility of animal models to evaluate

  12. The importance of large animal models in transplantation.

    PubMed

    Dehoux, Jean-Paul; Gianello, Pierre

    2007-09-01

    Animal models have been extensively used in transplantation research. However, animal experimentation is contentious and subject to legal and ethical restrictions. Most experiments are carried out on rodents, but crucial prerequisites for the development of safe pre-clinical protocols in biomedical research are needed through suitable large animal models. In transplantation particularly, large animal models have developed dramatically. This article provides an overview of the large animal models commonly used to evaluate organ transplant experiments and analyzes the specificity of several models in various situations such as induction of allospecific tolerance and xenotransplantation. The key determination that remains be addressed is the most appropriate species and strains to model human immune and physiological systems. Because of their phylogenetic and physiologic similarities to man, non-human primates play an increasingly important role in pre-clinical testing. Nevertheless, a number of studies have shown the pig to be a reliable large animal model for transplantation research, and the availability of genetically defined or modified pigs establishes a stronger position for pigs as a large animal model.

  13. Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics.

    PubMed

    Vestergaard, Bill; Agersø, Henrik; Lykkesfeldt, Jens

    2013-08-01

    Early understanding of the pharmacokinetics and metabolic patterns of new drug candidates is essential for selection of optimal candidates to move further in to the drug development process. In vitro methodologies can be used to investigate metabolic patterns, but in general, they lack several aspects of the whole-body physiology. In contrast, the complexity of intact animals does not necessarily allow individual processes to be identified. Animal models lacking a major excretion organ can be used to investigate these individual metabolic processes. Animal models of nephrectomy and hepatectomy have considerable potential as tools in preclinical pharmacokinetics to assess organs of importance for drug clearance and thereby knowledge of potential metabolic processes to manipulate to improve pharmacokinetic properties of the molecules. Detailed knowledge of anatomy and surgical techniques is crucial to successfully establish the models, and a well-balanced anaesthesia and adequate monitoring of the animals are also of major importance. An obvious drawback of animal models lacking an organ is the disruption of normal homoeostasis and the induction of dramatic and ultimately mortal systemic changes in the animals. Refining of the surgical techniques and the post-operative supportive care of the animals can increase the value of these models by minimizing the systemic changes induced, and thorough validation of nephrectomy and hepatectomy models is needed before use of such models as a tool in preclinical pharmacokinetics. The present MiniReview discusses pros and cons of the available techniques associated with establishing nephrectomy and hepatectomy models.

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

    PubMed

    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.

  15. Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes

    PubMed Central

    Wang, Bingxuan; P., Charukeshi Chandrasekera; Pippin, John J.

    2014-01-01

    Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor-based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management. PMID:24809394

  16. Large animal models in experimental knee sports surgery: focus on clinical translation.

    PubMed

    Madry, Henning; Ochi, Mitsuo; Cucchiarini, Magali; Pape, Dietrich; Seil, Romain

    2015-12-01

    Large animal models play a crucial role in sports surgery of the knee, as they are critical for the exploration of new experimental strategies and the clinical translation of novel techniques. The purpose of this contribution is to provide critical aspects of relevant animal models in this field, with a focus on paediatric anterior cruciate ligament (ACL) reconstruction, high tibial osteotomy, and articular cartilage repair. Although there is no single large animal model strictly replicating the human knee joint, the sheep stifle joint shares strong similarities. Studies in large animal models of paediatric ACL reconstruction identified specific risk factors associated with the different surgical techniques. The sheep model of high tibial osteotomy is a powerful new tool to advance the understanding of the effect of axial alignment on the lower extremity on specific issues of the knee joint. Large animal models of both focal chondral and osteochondral defects and of osteoarthritis have brought new findings about the mechanisms of cartilage repair and treatment options. The clinical application of a magnetic device for targeted cell delivery serves as a suitable example of how data from such animal models are directly translated into in clinical cartilage repair. As novel insights from studies in these translational models will advance the basic science, close cooperation in this important field of clinical translation will improve current reconstructive surgical options and open novel avenues for regenerative therapies of musculoskeletal disorders.

  17. Animal models of henipavirus infection: a review.

    PubMed

    Weingartl, Hana M; Berhane, Yohannes; Czub, Markus

    2009-09-01

    Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level four pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarises current published data relating to experimental infection of small and large animals, including the natural reservoir species, the Pteropus bat, with HeV or NiV. Susceptibility to infection and virus distribution in the individual species is discussed, along with the pathogenesis, pathological changes, and potential routes of transmission.

  18. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  19. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  20. Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291

    PubMed Central

    Winston, Jenessa A.; Thanissery, Rajani; Montgomery, Stephanie A.; Theriot, Casey M.

    2017-01-01

    Clostridium difficile is an anaerobic, gram-positive, spore-forming enteric pathogen that is associated with increasing morbidity and mortality and consequently poses an urgent threat to public health. Recurrence of a C. difficile infection (CDI) after successful treatment with antibiotics is high, occurring in 20–30% of patients, thus necessitating the discovery of novel therapeutics against this pathogen. Current animal models of CDI result in high mortality rates and thus do not approximate the chronic, insidious disease manifestations seen in humans with CDI. To evaluate therapeutics against C. difficile, a mouse model approximating human disease utilizing a clinically-relevant strain is needed. This protocol outlines the cefoperazone mouse model of CDI using a clinically-relevant and genetically-tractable strain, R20291. Techniques for clinical disease monitoring, C. difficile bacterial enumeration, toxin cytotoxicity, and histopathological changes throughout CDI in a mouse model are detailed in the protocol. Compared to other mouse models of CDI, this model is not uniformly lethal at the dose administered, allowing for the observation of a prolonged clinical course of infection concordant with the human disease. Therefore, this cefoperazone mouse model of CDI proves a valuable experimental platform to assess the effects of novel therapeutics on the amelioration of clinical disease and on the restoration of colonization resistance against C. difficile. PMID:28060346

  1. Comparative and alternative approaches and novel animal models for aging research

    PubMed Central

    Kristan, D. M.

    2008-01-01

    This special issue of AGE showcases powerful alternative or unconventional approaches to basic aging research, including the use of exceptionally long-lived animal model species and comparative methods from evolutionary biology. In this opening paper, we introduce several of these alternative aging research themes, including the comparative phylogenetic approach. This approach applies modern inferential methods for dissecting basic physiological and biochemical mechanisms correlated with phenotypic traits including longevity, slow aging, sustained somatic maintenance, and repair of molecular damage. Comparative methods can be used to assess the general relevance of specific aging mechanisms—including oxidative processes—to diverse animal species, as well as to assess their potential clinical relevance to humans and other mammals. We also introduce several other novel, underexploited approaches with particular relevance to biogerontology, including the use of model animal species or strains that retain natural genetic heterogeneity, studies of effects of infectious disease and parasites on aging and responses to caloric restriction, studies of reproductive aging, and naturally occurring sex differences in aging. We emphasize the importance of drawing inferences from aging phenomena in laboratory studies that can be applied to clinically relevant aging syndromes in long-lived, outbred animals, including humans. PMID:19424857

  2. Animal models for dengue vaccine development and testing.

    PubMed

    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.

  3. Preclinical animal models of multiple myeloma

    PubMed Central

    Lwin, Seint T; Edwards, Claire M; Silbermann, Rebecca

    2016-01-01

    Multiple myeloma is an incurable plasma-cell malignancy characterized by osteolytic bone disease and immunosuppression. Murine models of multiple myeloma and myeloma bone disease are critical tools for an improved understanding of the pathogenesis of the disease and the development of novel therapeutic strategies. This review will cover commonly used immunocompetent and xenograft models of myeloma, describing the advantages and disadvantages of each model system. In addition, this review provides detailed protocols for establishing systemic and local models of myeloma using both murine and human myeloma cell lines. PMID:26909147

  4. Current animal models of obsessive compulsive disorder: an update.

    PubMed

    Albelda, N; Joel, D

    2012-06-01

    During the last 30 years there have been many attempts to develop animal models of obsessive compulsive disorder (OCD), in the hope that they may provide a route for furthering our understanding and treatment of this disorder. The present review provides the reader with an overview of the currently active animal models of OCD, their strengths and limitations, so that the reader can use the review as a guide for establishing new animal models of OCD, evaluating existing animal models and choosing among them according to one's needs. We review current genetic, pharmacological, neurodevelopmental and behavioral animal models of OCD, and evaluate their face validity (derived from phenomenological similarity between the behavior in the animal model and the specific symptoms of the human condition), predictive validity (derived from similarity in response to treatment) and construct validity (derived from similarity in the underlying mechanisms [physiological or psychological]). On the basis of this evaluation we discuss the usefulness of the different models for screening drugs for anti-compulsive activity, detecting new targets for high frequency stimulation, studying the neural mechanisms of OCD and unraveling the role of gonadal hormones. We then describe potential new treatment strategies that emerge from the convergence of data obtained in different models on the one hand, and how different models can be used to model different subtypes or dimensions of OCD, on the other hand.

  5. The guinea pig as an animal model for developmental and reproductive toxicology studies.

    PubMed

    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.

  6. Recent advances in animal model experimentation in autism research.

    PubMed

    Tania, Mousumi; Khan, Md Asaduzzaman; Xia, Kun

    2014-10-01

    Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model