Rogers, Christopher S
Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. PMID:27367161
Yu Shuhao; Zheng Lulu; Li Yun; Li Chunyan; Ma Chenchen; Li Yixue; Li Xuan; Hao Pei
Abstract Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible an...
Vamathevan, Jessica J., E-mail: firstname.lastname@example.org [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)
Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.
Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns
Yin, Wu; Carballo-Jane, Ester; McLaren, David G; Mendoza, Vivienne H; Gagen, Karen; Geoghagen, Neil S; McNamara, Lesley Ann; Gorski, Judith N; Eiermann, George J; Petrov, Aleksandr; Wolff, Michael; Tong, Xinchun; Wilsie, Larissa C; Akiyama, Taro E; Chen, Jing; Thankappan, Anil; Xue, Jiyan; Ping, Xiaoli; Andrews, Genevieve; Wickham, L Alexandra; Gai, Cesaire L; Trinh, Tu; Kulick, Alison A; Donnelly, Marcie J; Voronin, Gregory O; Rosa, Ray; Cumiskey, Anne-Marie; Bekkari, Kavitha; Mitnaul, Lyndon J; Puig, Oscar; Chen, Fabian; Raubertas, Richard; Wong, Peggy H; Hansen, Barbara C; Koblan, Ken S; Roddy, Thomas P; Hubbard, Brian K; Strack, Alison M
In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profiles, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study. PMID:22021650
Full Text Available Using mixed-species bird flocks as an example, we model the payoffs for two types of species from participating in multi-species animal groups. Salliers feed on mobile prey, are good sentinels and do not affect prey capture rates of gleaners; gleaners feed on prey on substrates and can enhance the prey capture rate of salliers by flushing prey, but are poor sentinels. These functional types are known from various animal taxa that form multi-species associations. We model costs and benefits of joining groups for a wide range of group compositions under varying abundances of two types of prey-prey on substrates and mobile prey. Our model predicts that gleaners and salliers show a conflict of interest in multi-species groups, because gleaners benefit from increasing numbers of salliers in the group, whereas salliers benefit from increasing gleaner numbers. The model also predicts that the limits to size and variability in composition of multi-species groups are driven by the relative abundance of different types of prey, independent of predation pressure. Our model emphasises resources as a primary driver of temporal and spatial group dynamics, rather than reproductive activity or predation per se, which have hitherto been thought to explain patterns of multi-species group formation and cohesion. The qualitative predictions of the model are supported by empirical patterns from both terrestrial and marine multi-species groups, suggesting that similar mechanisms might underlie group dynamics in a range of taxa. The model also makes novel predictions about group dynamics that can be tested using variation across space and time.
Gøtze, Jens Peter; Krentz, Andrew
In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...
Wang, Yingying; Cai, Yunpeng
Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID:27407070
Olsson, I. Anna S.; Sandøe, Peter
are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who......This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... bears responsibility for the use of animals in disease models?...
Xiao-Jiang Li; Shihua Li
Transgenic animal models have revealed much about the pathogenesis of age-dependent neurodegenerative diseases and proved to be a useful tool for uncovering therapeutic targets.Huntington's disease is a well-characterized neurodegenerative disorder that is caused by expansion of a CAG repeat,which results in expansion of a polyglutamine tract in the N-terminal region of huntingtin (HTT).Similar CAG/glutamine expansions are also found to cause eight other neurodegenerative diseases that affect distinct brain regions in an agedependent manner.Identification of this CAG/glutamine expansion has led to the generation of a variety of transgenic animal models.Of these different animal models,transgenic mice have been investigated extensively,and they show similar neuropathology and phenotypes as seen in their respective diseases.The common pathological hallmark of age-dependent neurodegeneration is the formation of aggregates or inclusions consisting of misfolded proteins in the affected brain regions; however,overt or striking neurodegeneration and apoptosis have not been reported in most transgenic mouse models for age-dependent diseases,including HD.By comparing the neuropathology of transgenic HD mouse,pig,and monkey models,we found that mutant HTT is more toxic to larger animals than mice,and larger animals also show neuropathology that has not been uncovered by transgenic mouse models.This review will discuss the importancc of transgenic large animal models for analyzing the pathogenesis of neurodegenerative diseases and developing effective treatments.
DeLellis, P.; G. Polverino; Ustuner, G.; Abaid, N.; Macri, S.; Bollt, E. M.; M. Porfiri
We posit a new geometric perspective to define, detect, and classify inherent patterns of collective behaviour across a variety of animal species. We show that machine learning techniques, and specifically the isometric mapping algorithm, allow the identification and interpretation of different types of collective behaviour in five social animal species. These results offer a first glimpse at the transformative potential of machine learning for ethology, similar to its impact on robotics, whe...
Delellis, Pietro; Polverino, Giovanni; Ustuner, Gozde; Abaid, Nicole; Macrì, Simone; Bollt, Erik M.; Porfiri, Maurizio
We posit a new geometric perspective to define, detect, and classify inherent patterns of collective behaviour across a variety of animal species. We show that machine learning techniques, and specifically the isometric mapping algorithm, allow the identification and interpretation of different types of collective behaviour in five social animal species. These results offer a first glimpse at the transformative potential of machine learning for ethology, similar to its impact on robotics, where it enabled robots to recognize objects and navigate the environment.
Yin, Wu; Carballo-Jane, Ester; McLaren, David G.; Mendoza, Vivienne H.; Gagen, Karen; Geoghagen, Neil S.; McNamara, Lesley Ann; Gorski, Judith N.; Eiermann, George J.; Petrov, Aleksandr; Wolff, Michael; Tong, Xinchun; Wilsie, Larissa C.; Akiyama, Taro E.; Chen, Jing; Thankappan, Anil; Xue, Jiyan; Ping, Xiaoli; Andrews, Genevieve; Wickham, L. Alexandra; Gai, Cesaire L.; Trinh, Tu; Kulick, Alison A.; Donnelly, Marcie J.; Voronin, Gregory O.; Rosa, Ray; Cumiskey, Anne-Marie; Bekkari, Kavitha; Mitnaul, Lyndon J.; Puig, Oscar; Chen, Fabian; Raubertas, Richard; Wong, Peggy H.; Hansen, Barbara C.; Koblan, Ken S.; Roddy, Thomas P.; Hubbard, Brian K; Strack, Alison M.
In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profiles, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study. PMID:22021650
Brayden, David J; Oudot, Emilie J M; Baird, Alan W
Delivery of biologically active agents to animals is often perceived to be the poor relation of human drug delivery. Yet this field has a long and successful history of species-specific device and formulation development, ranging from simple approaches and devices used in production animals to more sophisticated formulations and approaches for a wide range of species. While several technologies using biodegradable polymers have been successfully marketed in a range of veterinary and human products, the transfer of delivery technologies has not been similarly applied across species. This may be due to a combination of specific technical requirements for use of devices in different species, inter-species pharmacokinetic, pharmacodynamic and physiological differences, and distinct market drivers for drug classes used in companion and food-producing animals. This chapter reviews selected commercialised and research-based parenteral and non-parenteral veterinary drug delivery technologies in selected domestic species. Emphasis is also placed on the impact of endogenous drug transporters on drug distribution characteristics in different species. In vitro models used to investigate carrier-dependent transport are reviewed. Species-specific expression of transporters in several tissues can account for inter-animal or inter-species pharmacokinetic variability, lack of predictability of drug efficacy, and potential drug-drug interactions. PMID:20204584
Gröning, Julia; Hochkirch, Axel
Although sexual interactions between species (reproductive interference) have been reported from a wide range of animal taxa, their potential for determining species coexistence is often disregarded. Here, we review evidence from laboratory and field studies illustrating that heterospecific sexual interactions are frequently associated with fitness loss and can have severe ecological and evolutionary consequences. We define reproductive interference as any kind of interspecific interaction during the process of mate acquisition that adversely affects the fitness of at least one of the species involved and that is caused by incomplete species recognition. We distinguish seven types of reproductive interference: signal jamming, heterospecific rivalry, misdirected courtship, heterospecific mating attempts, erroneous female choice, heterospecific mating, and hybridization. We then discuss the sex-specific costs of these types and highlight two typical features of reproductive interference: density-dependence and asymmetry. Similar to competition, reproductive interference can lead to displacement of one species (sexual exclusion), spatial, temporal, or habitat segregation, changes in life history parameters, and reproductive character displacement. In many cases, patterns of coexistence might be shaped by reproductive interference rather than by resource competition, as the presence of a few heterospecifics might substantially decrease reproductive success. Therefore, interspecific sexual interactions should receive more attention in ecological research. Reproductive interference has mainly been discussed in the context of invasive species or hybrid zones, whereas its influence on naturally-occurring sympatric species pairs has rarely been addressed. To improve our knowledge of the ecological significance of reproductive interference, findings from laboratory experiments should be validated in the field. Future studies should also focus on ecological mechanisms, such
Brozoski, Thomas J; Bauer, Carol A
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
Croft, Barbara Y.
Animal models can be used in the study of disease. This chapter discusses imaging animal models to elucidate the process of human disease. The mouse is used as the primary model. Though this choice simplifies many research choices, it necessitates compromises for in vivo imaging. In the future, we can expect improvements in both animal models and imaging techniques.
Bates, Jason H.T.; Rincon, Mercedes; Irvin, Charles G.
Studies in animal models form the basis for much of our current understanding of the pathophysiology of asthma, and are central to the preclinical development of drug therapies. No animal model completely recapitulates all features of the human disease, however. Research has focused primarily on ways to generate allergic inflammation by sensitizing and challenging animals with a variety of foreign proteins, leading to an increased understanding of the immunological factors that mediate the in...
Tsuyoshi Shimamura; Nobuo Kubota; Kazutoshi Shibuya
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 presen...
Langrock, Roland; Hopcraft, Grant; Blackwell, Paul; Goodall, Victoria; King, Ruth; Niu, Mu; Patterson, Toby; Pedersen, Martin; Skarin, Anna; Schick, Robert Schilling
1). Group dynamics are a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognized, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However, to date, practical statistical methods, which can include group dynamics in animal movement models, have been lacking. 2). We consider a flexible modelling framework that distinguishes a group-level ...
Nagakura, Yukinori; Ito, Hiroyuki; Shimizu, Yasuaki
Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. T...
Jones, CA; Watson, DJG; Fone, KCF
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 rod...
Picard, Brigitte; Lefaucheur, Louis; Berri, Cécile; Duclos, Michel
International audience In farm animals (bovine, ovine, swine, rabbit and poultry), muscle fibre characteristics play a key role in meat quality. The present review summarises the knowledge on muscle fibre characteristics and ontogenesis in these species. Myofibre ontogenesis begins very early during embryonic life, with the appearance of two or three successive waves of myoblasts which constitute the origin of the different types of muscle fibres. In small animals (rodents and poultry), a ...
Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.
Bari, A; Robbins, T W
Studies employing animal models of attention-deficit/hyperactivity disorder (ADHD) present clear inherent advantages over human studies. Animal models are invaluable tools for the study of underlying neurochemical, neuropathological and genetic alterations that cause ADHD, because they allow relatively fast, rigorous hypothesis testing and invasive manipulations as well as selective breeding. Moreover, especially for ADHD, animal models with good predictive validity would allow the assessment of potential new therapeutics. In this chapter, we describe and comment on the most frequently used animal models of ADHD that have been created by genetic, neurochemical and physical alterations in rodents. We then discuss that an emerging and promising direction of the field is the analysis of individual behavioural differences among a normal population of animals. Subjects presenting extreme characteristics related to ADHD can be studied, thereby avoiding some of the problems that are found in other models, such as functional recovery and unnecessary assumptions about aetiology. This approach is justified by the theoretical need to consider human ADHD as the extreme part of a spectrum of characteristics that are distributed normally in the general population, as opposed to the predominant view of ADHD as a separate pathological category. PMID:21287324
Simple Summary When making a choice of species for animal experimentation we must balance its suitability as a model for human medicine against the potential harms to the animals both from the procedures and the quality of their lifetime experience. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primate...
Redner, Sidney; Clauset, Aaron; Schwab, David
We develop a simple diffusion-reaction model to account for the broad and asymmetric distribution of adult body masses for species within related taxonomic groups. The model assumes three basic evolutionary features that control body mass: (i) a fixed lower limit that is set by metabolic constraints, (ii) a species extinction risk that is a weakly increasing function of body mass, and (iii) cladogenetic diffusion, in which daughter species have a slight tendency toward larger mass. The steady-state solution for the distribution of species masses in this model can be expressed in terms of the Airy function. This solution gives mass distributions that are in good agreement with data on 4002 terrestrial mammal species from the late Quaternary and 8617 extant bird species.
Godfrey S Getz; Reardon, Catherine A
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...
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.
Fink, Mitchell P.
Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, ...
Chen, Lichao; Brown, Ritchie E.; McKenna, James T.; McCARLEY, ROBERT W.
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 sy...
Porter, W P; Ostrowski, S; Williams, J B
There is an increasing need to assess the effects of climate and land-use change on habitat quality, ideally from a mechanistic basis. The symposium "Molecules to Migration: Pressures of Life" at the Fourth International Conference in Africa for Comparative Physiology and Biochemistry, Maasai Mara National Reserve, Kenya, 2008, illustrated how the principles of biophysical ecology can capture the mechanistic links between organisms, climate, and other habitat features. These principles provide spatially explicit assessments of habitat quality from a physiological perspective (i.e., "animal landscapes") that can be validated independently of the data used to derive and parameterize them. The contents of this symposium showcased how the modeling of animal landscapes can be used to assess key issues in applied and theoretical ecology. The presentations included applications to amphibians, reptiles, birds, and mammals. The rare Arabian oryx on the Arabian Peninsula is used as an example for energetic calculations and their implications for behavior on the landscape. PMID:20670170
Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre
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 pr...
Bhattacharya, Sukanto; Malakar, Sreepurna
Our paper computationally explores the extinction dynamics of an animal species effected by a sudden spike in mortality due to an extreme event. In our study, the animal species has a 2-year life cycle and is endowed with a high survival probability under normal circumstances. Our proposed approach does not involve any restraining assumptions concerning environmental variables or predator-prey relationships. Rather it is based on the simple premise that if observed on an year-to-year basis, t...
Full Text Available Abstract 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
Ericsson, Aaron C.; Crim, Marcus J; Franklin, Craig L.
Comparative medicine is founded on the concept that other animal species share physiological, behavioral, or other characteristics with humans. Over 2,400 years ago it was recognized that by studying animals, we could learn much about ourselves. This technique has now developed to the point that animal models are employed in virtually all fields of biomedical research including, but not limited to, basic biology, immunology and infectious disease, oncology, and behavior.
Samuel H. Preston; Laurie Bingaman Lackey; Iliana Kohler
We present life tables by single year of age and sex for groups of animals and for 42 individual mostly mammalian species. Data are derived from the International Species Information System. The survivorship of most of these species has never been mapped systematically. We demonstrate that, in most of the groups, female survivorship significantly exceeds that of males above age five. Wild-born animals do not have mortality that differs significantly from captive-born animals. While most speci...
Smouse, Peter E.; Focardi, Stefano; Moorcroft, Paul R.; Kie, John G.; Forester, James D.; Morales, Juan M.
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 poi...
Nestler, Eric J.; Steven E Hyman
Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many key symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression, a...
Knegtering, Edo; van der Windt, Henny J.; Schoot Uiterkamp, Anton J. M.
Systematic knowledge about factors affecting the willingness of societies to conserve biodiversity is still scarce. This study investigates the role of body size in national decisions on wild animal species by analysing the average body sizes of the animal species subject to species-specific legisla
Johnson, Robert L.; Fleet, James C.
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
The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress. It may also refer to procedures used to enhance animal comfort. This paper summarizes considerations for refinements in research animal.
Liechty ER; Bergin IL; Bell JD
Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic co...
Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologi...
Sidney D'MELLO, Stan FRANKLIN
Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].
Wilson, Bethany K.; Hess, Ellen J.
Symptomatic animal models have clinical features consistent with human disorders and are often used to identify the anatomical and physiological processes involved in the expression of symptoms and to experimentally demonstrate causality where it would be infeasible in the patient population. Rodent and primate models of dystonia have identified basal ganglia abnormalities, including alterations in striatal GABAergic and dopaminergic transmission. Symptomatic animal models have also establish...
Khodanovich, M. Yu.; Kisel, A. A.
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.
Nikitidou, Olga; Peppa, Vasiliki I.; Leivaditis, Konstantinos; Eleftheriadis, Theodoros; Zarogiannis, Sotirios G.; Liakopoulos, Vassilios
Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use. PMID:26388781
Full Text Available Peritoneal dialysis (PD has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease. In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.
Roy, Chad J; Song, Kejing; Sivasubramani, Satheesh K.; Gardner, Donald J.; Seth H Pincus
Animal models of ricin toxicosis are necessary for testing the efficacy of therapeutic measures, as well studying the mechanisms by which ricin exerts its toxicity in intact animals. Because ricin can serve as a particularly well-characterized model of tissue damage, and the host response to that damage, studies of the mechanisms of ricin toxicity may have more general applicability. For example, our studies of the molecular mechanisms underlying the development of ricin-induced hypoglycemia ...
Rust, J H
The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator
Juan G Abraldes; Marcos Pasarín; Juan Carlos; García-Pagán
Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model,depending on the specific objectives of the study, are also discussed.
Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L
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.
ABSTRACT: Allergic disease such as asthma, rhinitis, and eczema are increasing prevelanceand affect up to 15% of population in Westernized countries. Among them, asthma is achronic inflammatory disease of airways and the underlying physiological and immunologicalprocesses are not fully understood. Mouse models of asthma dupicates many featuresof human asthma, including airway hyperreactivity, andairway inflammation. Therefore, relevantmodels for asthma are important to understand the mechanis...
Schaeffel, Frank; Feldkaemper, Marita
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. PMID:26769177
Schäffer, Alejandro A.; Klein, Christoph
In vivo animal models have proven very useful to understand basic biological pathways of the immune system, a prerequisite for the development of innovate therapies. This manuscript addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve di...
Eva Harris; Simona Zompi
The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe deng...
Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi;
As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are...... important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...
Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.;
, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual...... makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias...... in an encamped state. Though the attraction to the group centroid is relatively weak, our model successfully captures group-influenced movement dynamics. Specifically, as compared to a regular mixture of correlated random walks, the group dynamic model more accurately predicts the non-diffusive behaviour...
Animal models have been used to provide insight into the complex immunological and pathophysioligical mechanisms of human Type 1 allergic diseases. Research efforts that include mechanistic studies in search of new therapies and screening models for hazard identification of potential allergens in a...
Full Text Available Marxism has been justifiably skeptical of animal rights. Indeed, deep ecology and animal-rights discourse are, in their native habitats, deeply problematic and self-contradictory. But recent theories of “bare life,” when brought into dialogue with Marx’s concept of species-being, offer a perspective from which animal rights discourse and Marxism share a common political horizon.
Krnjaja V.; Lević J.; Stanković S.
Numerous plant species, which are main components of various mixtures used in animal nutrition, can be contaminated by mycotoxins created by large number of pathogenic and toxigenic fungi (moulds). From the aspect of animal nutrition, most important are cereals and oil crops (in form of meals) because they constitute the highest share in preparation of animal food, and on the other hand, they are especially sensitive to toxigenic fungi and can contain mycot...
Marxism has been justifiably skeptical of animal rights. Indeed, deep ecology and animal-rights discourse are, in their native habitats, deeply problematic and self-contradictory. But recent theories of “bare life,” when brought into dialogue with Marx’s concept of species-being, offer a perspective from which animal rights discourse and Marxism share a common political horizon.
Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta
Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993
Muñoz-Colmenero, Marta; Martínez, Jose Luis; Roca, Agustín; Garcia-Vazquez, Eva
Candy products are consumed all across the world, but there is not much information about their composition. In this study we have used a DNA-based approach for determining the animal species occurring in 40 commercial candies of different types. We extracted DNA and performed PCR amplification, cloning and sequencing for obtaining species-informative DNA sequences. Eight species were identified including fish (hake and anchovy) in 22% of the products analyzed. Bovine and porcine were the most abundant appearing in 27 samples each one. Most products contained a mixture of species. Marshmallows (7), jelly-types, and gummies (20) contained a significantly higher number of species than hard candies (9). We demonstrated the presence of DNA animal species in candy product which allow consumers to make choices and prevent allergic reaction. PMID:26807698
There is intense interest in the development and application of animal models of CNS disorders to explore pathology and molecular mechanisms, identify potential biomarkers, and to assess the therapeutic utility, estimate safety margins and establish pharmacodynamic and pharmacokinetic parameters of new chemical entities (NCEs). This is a daunting undertaking, due to the complex and heterogeneous nature of these disorders, the subjective and sometimes contradictory nature of the clinical endpoints and the paucity of information regarding underlying molecular mechanisms. Historically, these models have been invaluable in the discovery of therapeutics for a range of disorders including anxiety, depression, schizophrenia, and Parkinson's disease. Recently, however, they have been increasingly criticized in the wake of numerous clinical trial failures of NCEs with promising preclinical profiles. These failures have resulted from a number of factors including inherent limitations of the models, over-interpretation of preclinical results and the complex nature of clinical trials for CNS disorders. This review discusses the rationale, strengths, weaknesses and predictive validity of the most commonly used models for psychiatric, neurodegenerative and neurological disorders as well as critical factors that affect the variability and reproducibility of these models. It also addresses how progress in molecular genetics and the development of transgenic animals has fundamentally changed the approach to neurodegenerative disorder research. To date, transgenic animal models\\have not been the panacea for drug discovery that many had hoped for. However continual refinement of these models is leading to steady progress with the promise of eventual therapeutic breakthroughs. PMID:23811310
Joséphine eReynaud; Branka eHorvat
Human herpesvirus (HHV)-6A and HHV-6B are two enveloped DNA viruses of β-herpesvirus family, infecting over 90% of the population and associated with several diseases, including exanthema subitum (for HHV-6B), multiple sclerosis and encephalitis, particularly in immunosuppressed patients. Animal models are highly important to better understand the pathogenesis of viral infections. Naturally developed neutralizing antibodies to HHV-6 or a related virus were found in different species of monkey...
Osborne, Lucy R.
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,...
ZHANG Chao; WANG Qiuju; SUN Wei
The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models re-garding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Re-liable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been pro-posed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned re-sponse suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.
Morton, A Jennifer; Howland, David S
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. PMID:25063426
Barkley-Levenson, Amanda M.; Crabbe, John C.
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 ...
Kim, Sangwon F.
Feeding is a fundamental process for basic survival, and is influenced by genetics and environmental stressors. Recent advances in our understanding of behavioral genetics have provided a profound insight on several components regulating eating patterns. However, our understanding of eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating is still poor. The animal model is an essential tool in the investigation of eating behaviors and their pathological forms, yet develop...
Patterson, Paul H.
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...
Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G
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...
Veazey, Ronald S.; Shattock, Robin J.; Klasse, Per Johan; Moore, John P.
There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.
Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes
Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development for...... headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...
Full Text Available Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. Keywords: nonhuman primate, preclinical, in vivo, contraceptive devices
Kévin P. Dhondt
Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.
Dhondt, Kévin P; Horvat, Branka
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
Ethical principles governing the conduct of experiments with animals are reviewed, especially those relating to the choice of species. Legislation requires that the potential harm to animals arising from any procedure should be assessed in advance and justified in terms of its possible benefit to society. Potential harms may arise both from the procedures and the quality of the animals' lifetime experience. The conventional approach to species selection is to use animals with the "lowest degree of neurophysiological sensitivity". However; this concept should be applied with extreme caution in the light of new knowledge. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. A set of responsibilities is outlined for each category of moral agent. These include regulators, operators directly concerned with the conduct of scientific experiments and toxicology trials, veterinarians and animal care staff; and society at large. PMID:26479009
Thomas J. STOHLGREN; Catherine S. JARNEVICH; Wayne E. ESAIAS; Jeffrey T. MORISETTE
Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern.Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development,yet there is no recommended best practice for “clamping” model extrapolations.We relied on two commonly used modeling approaches:classification and regression tree (CART) and maximum entropy (Maxent) models,and we tested a simple alteration of the model extrapolations,bounding extrapolations to the maximum and minimum values of primary environmental predictors,to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States.Findings suggest that multiple models of bounding,and the most conservative bounding of species distribution models,like those presented here,should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5):642-647,2011].
Yoder, Bradley A.; Coalson, Jacqueline J.
Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the...
Full Text Available Ethical principles governing the conduct of experiments with animals are reviewed, especially those relating to the choice of species. Legislation requires that the potential harm to animals arising from any procedure should be assessed in advance and justified in terms of its possible benefit to society. Potential harms may arise both from the procedures and the quality of the animals’ lifetime experience. The conventional approach to species selection is to use animals with the “lowest degree of neurophysiological sensitivity”. However; this concept should be applied with extreme caution in the light of new knowledge. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. A set of responsibilities is outlined for each category of moral agent. These include regulators, operators directly concerned with the conduct of scientific experiments and toxicology trials, veterinarians and animal care staff; and society at large.
Nordquist Rebecca E; Arndt Saskia S; van der Staay F Josef
Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentiall...
Hebert, Paul D N; Ratnasingham, Sujeevan; Zakharov, Evgeny V; Telfer, Angela C; Levesque-Beaudin, Valerie; Milton, Megan A; Pedersen, Stephanie; Jannetta, Paul; deWaard, Jeremy R
Recent estimates suggest that the global insect fauna includes fewer than six million species, but this projection is very uncertain because taxonomic work has been limited on some highly diverse groups. Validation of current estimates minimally requires the investigation of all lineages that are diverse enough to have a substantial impact on the final species count. This study represents a first step in this direction; it employs DNA barcoding to evaluate patterns of species richness in 27 orders of Canadian insects. The analysis of over one million specimens revealed species counts congruent with earlier results for most orders. However, Diptera and Hymenoptera were unexpectedly diverse, representing two-thirds of the 46 937 barcode index numbers (=species) detected. Correspondence checks between known species and barcoded taxa showed that sampling was incomplete, a result confirmed by extrapolations from the barcode results which suggest the occurrence of at least 94 000 species of insects in Canada, a near doubling from the prior estimate of 54 000 species. One dipteran family, the Cecidomyiidae, was extraordinarily diverse with an estimated 16 000 species, a 10-fold increase from its predicted diversity. If Canada possesses about 1% of the global fauna, as it does for known taxa, the results of this study suggest the presence of 10 million insect species with about 1.8 million of these taxa in the Cecidomyiidae. If so, the global species count for this fly family may exceed the combined total for all 142 beetle families. If extended to more geographical regions and to all hyperdiverse groups, DNA barcoding can rapidly resolve the current uncertainty surrounding a species count for the animal kingdom. A newly detailed understanding of species diversity may illuminate processes important in speciation, as suggested by the discovery that the most diverse insect lineages in Canada employ an unusual mode of reproduction, haplodiploidy.This article is part of the
Köksal, Falih; Domjan, Michael; Kurt, Adnan; Sertel, Ozlem; Orüng, Sabiha; Bowers, Rob; Kumru, Gulsen
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. PMID:15500813
Pommergaard, Hans-Christian; Rosenberg, J; Schumacher-Petersen, Camilla;
Animal models are valuable for studying pathogenic factors and preventive measures for colon anastomotic leakage. The suitability of the species as models varies greatly; however, no consensus exists on which species to use. The aim of this review was to evaluate different experimental animals for...
Croda, Julio; Figueira, Claudio Pereira; Wunder, Elsio A; Santos, Cleiton S; Reis, Mitermayer G; Ko, Albert I; Picardeau, Mathieu
The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization. PMID:18809657
Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K
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. PMID:26265551
Full Text Available An alternative DNA detection system is based on the polymerase chain reaction (PCR amplification of a segment of the mitochondrial cytochrome b gene. Subsequent cleavage by a restriction enzymes gives rise to a specie-specific pattern on an agarose gel. We used five animal species (Mustela vison, Mustela putorius furo, Sus scrofa domesticus, Oryctolagus cuninculus, Anser anser. Length of PCR product was 359 bp and we used universal primers. Restriction fragment length polymorphism was analyzed by using the restriction endonuclease AluI. Results of cleavage were visualized by using electrophoresis and UV transiluminator. Every animal specie has a unique combination of restriction fragments i.e. Mustela vison 81 bp, 109 bp and 169 bp, Mustela putorius furo 169 bp and 190 bp, Sus scrofa domesticus 115 bp and 244 bp, Oryctolagus cunninculus is not cleaved by AluI so it has whole 359 bp fragment on agarose gel, Anser anser 130 bp and 229 bp. The results suggest that the method of PCR - RFLP is rapid and simple method for identification of species. PCR – RFLP can reliably identify chosen species. Application of genetic methods is very useful for breeding of livestock and protection of biodiversity.
Full Text Available Wind farms are constructed in various areas without considering the protected animal species that are present there. In problem areas, there are some mitigation measures taken. In 55% of the studies, bird mortality rates ranges from 0.0 to 2.0 fatalities/turbine/year. 79.4% of the evaluated mortality rates for raptors range from 0.0 to 0.1 fatalities/ turbine/year. The highest number of wind turbine fatalities has been recorded with a raptor Buteo jamaicensis, followed by seagull Larus argentatus, passerine Eremophila alpestris and domestic pigeon Columbia livia. The only species that has been recorded as a wind turbine fatality and is a part of the IUCN Red list of Threatened Species is red kite (Milvus milvus. The European wind power studies pay more attention to the disturbance of particular species. The species that are most commonly considered threatened are the raptors (common buzzard, common kestrel and red kite, grassland birds (common quail, corn crake, lapwing, ringed plover, migrating birds (migrant goose, crane, lapwing, golden plover and waterbirds (geese species. Bat annual mortality rates range from 0.0 to 47.5 fatalities/turbine/year at different wind farms. The highest mortality rate has been reported for bat species Laisurus cinereus, Lasiurus borealis, Lasionycteris noctivagans and Nyctalus noctula.
Seitz, Guido; Armeanu-Ebinger, Sorin; WARMANN, STEVEN; Fuchs, Jörg
Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models tha...
Lelovas, Pavlos P; Xanthos, Theodoros T; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A
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 th...
Objective: To investigate the methods of inducing polymyosistis(PM) animal model. Methods: In order to develope a induce PM animal model in purified guinea pia muscle myosin mixed with complete Freund adjuvant was injected subcutaneously to SD rats many times and the results of the clinical finding, the EMG, the pathologic changes and the musclar MRI changes in SD rats was assessed. Results: The PM animal models were similar to the human in clinical findings, the EMG, the pathologic changes, the musclar MRI changes and so on. Conclusion: The animal model is similar to the human PM, it is an ideal animal model to investigate PM. (authors)
Carter, Anthony Michael
This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there...
Overby, Darryl R; Clark, Abbot F
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
Jürgen Götz; Naeman N Götz
In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as ...
Kostic, Corinne; Arsenijevic, Yvan
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. PMID:26387748
Le Borgne, Yvan; Marckert, Jean-François
In this paper, we revisit the enumeration of directed animals using gas models. We show that there exists a natural construction of random directed animals on any directed graph together with a particle system that explains at the level of objects the formal link known between the density of the gas model and the generating function of directed animals counted according to the area. This provides some new methods to compute the generating function of directed animals counted according to area...
Swartz, Daniel D.; Andreadis, Stelios T.
Due to rise in cardiovascular disease throughout the world, there is increasing demand for small diameter blood vessels as replacement grafts. The present review focuses on the animal models that have been used to test small-diameter TEVs with emphasis on the attributes of each model. Small animal models are used to test short-term patency and address mechanistic hypotheses; and large, pre-clinical animal models are employed to test long-term patency, remodeling and function in an environment...
Sterže Jana; Pogačnik M.
Wind farms are constructed in various areas without considering the protected animal species that are present there. In problem areas, there are some mitigation measures taken. In 55% of the studies, bird mortality rates ranges from 0.0 to 2.0 fatalities/turbine/year. 79.4% of the evaluated mortality rates for raptors range from 0.0 to 0.1 fatalities/ turbine/year. The highest number of wind turbine fatalities has been recorded with a raptor Buteo jamaicensis, followed by seagull Larus argent...
Zhang, Xueli; Tian, Yanli; Zhang, Can; Tian, Xiaoyu; Ross, Alana W.; Moir, Robert D.; Sun, Hongbin; Tanzi, Rudolph E.; Moore, Anna; Ran, Chongzhao
Drug development for Alzheimer’s disease (AD) has been largely unsuccessful to date. Although numerous agents are reportedly effective in vitro, only an inadequate number of them have been tested in vivo, partially because of the lack of reliable and cost-efficient imaging methods to monitor their in vivo therapeutic effectiveness. Several amyloid beta (Aβ)-specific PET tracers have been used for clinical studies. However, their application for monitoring drug treatment in small animals is li...
Gupta, U D; Katoch, V M
Animal models for testing different vaccine candidates have been developed since a long time for studying tuberculosis. Mice, guinea pigs and rabbits are animals most frequently used. Each model has its own merits for studying human tuberculosis, and none completely mimics the human disease. Different animal models are being used depending upon the availability of the space, trained manpower as well as other resources. Efforts should continue to develop a vaccine which can replace/outperform the presently available vaccine BCG. PMID:19287053
Stewart, Adam Michael; Kalueff, Allan V
Valid sensitive animal models are crucial for understanding the pathobiology of complex human disorders, such as anxiety, autism, depression and schizophrenia, which all have the 'spectrum' nature. Discussing new important strategic directions of research in this field, here we focus i) on cross-species validation of animal models, ii) ensuring their population (external) validity, and iii) the need to target the interplay between multiple disordered domains. We note that optimal animal models of brain disorders should target evolutionary conserved 'core' traits/domains and specifically mimic the clinically relevant inter-relationships between these domains. PMID:24384129
Bichet, Orphé; Dupuch, Angélique; Hébert, Christian; Le Borgne, Hélène Le; Fortin, Daniel
With the intensification of human activities, preserving animal populations is a contemporary challenge of critical importance. In this context, the umbrella species concept is appealing because preserving a single species should result in the protection of multiple co-occurring species. Practitioners, though, face the task of having to find suitable umbrellas to develop single-species management guidelines. In North America, boreal forests must be managed to facilitate the recovery of the threatened boreal caribou (Rangifer tarandus). Yet, the effect of caribou conservation on co-occurring animal species remains poorly documented. We tested if boreal caribou can constitute an effective umbrella for boreal fauna. Birds, small mammals, and insects were sampled along gradients of post-harvest and post-fire forest succession. Predictive models of occupancy were developed from the responses of 95 species to characteristics of forest stands and their surroundings. We then assessed the similarity of species occupancy expected between simulated harvested landscapes and a 90 000-km2 uncut landscape. Managed landscapes were simulated based on three levels of disturbance, two timber-harvest rotation cycles, and dispersed or aggregated cut-blocks. We found that management guidelines that were more likely to maintain caribou populations should also better preserve animal assemblages. Relative to fragmentation or harvest cycle, we detected a stronger effect of habitat loss on species assemblages. Disturbing 22%, 35%, and 45% of the landscape should result, respectively, in 80%, 60%, and 40% probability for caribou populations to be sustainable; in turn, this should result in regional species assemblages with Jaccard similarity indices of 0.86, 0.79, and 0.74, respectively, relative to the uncut landscape. Our study thus demonstrates the value of single-species management for animal conservation. Our quantitative approach allows for the evaluation of management guidelines prior
Nichols, J.D.; Boulinier, T.; Hines, J.E.; Pollock, K.H.; Sauer, J.R.
Species richness has been identified as a useful state variable for conservation and management purposes. Changes in richness over time provide a basis for predicting and evaluating community responses to management, to natural disturbance, and to changes in factors such as community composition (e.g., the removal of a keystone species). Probabilistic capture-recapture models have been used recently to estimate species richness from species count and presence-absence data. These models do not require the common assumption that all species are detected in sampling efforts. We extend this approach to the development of estimators useful for studying the vital rates responsible for changes in animal communities over time; rates of local species extinction, turnover, and colonization. Our approach to estimation is based on capture-recapture models for closed animal populations that permit heterogeneity in detection probabilities among the different species in the sampled community. We have developed a computer program, COMDYN, to compute many of these estimators and associated bootstrap variances. Analyses using data from the North American Breeding Bird Survey (BBS) suggested that the estimators performed reasonably well. We recommend estimators based on probabilistic modeling for future work on community responses to management efforts as well as on basic questions about community dynamics.
Full Text Available 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 and 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 categorised by animal species and are further classified by the setting of the infection. Study methods are summarised 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.
A I Pearce
Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.
Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.
Whitelaw, C. Bruce A.; Timothy P Sheets; Lillico, Simon G; Telugu, Bhanu P.
Abstract 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...
Peters, Suzanne M; Pothuizen, Helen H J; Spruijt, Berry M
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. PMID:25823814
Olesen, Jes; Jansen-Olesen, Inger
The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....
Ning Zhang; Marong Fang; Haohao Chen; Fangming Gou; Mingxing Ding
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.
Hraiech S; Papazian L.; Rolain JM; Bregeon F
Sami Hraiech,1,2 Laurent Papazian,1,2 Jean-Marc Rolain,1 Fabienne Bregeon1,3IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France; 2Réanimation – Détresses respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France; 3Service d’Explorations Fonctionnelles Respiratoires, APHM, CHU Nord, Marseille, FranceAbstract: Pneumonia is one of the leading causes of severe and occasion...
Rodent models for breast cancer have for many decades provided unparalleled insights into cellular and molecular aspects of neoplastic transformation and tumorigenesis. Despite recent improvements in the fidelity of genetically engineered mice, rodent models are still being criticized by many colleagues for not being 'authentic' enough to the human disease. Motives for this criticism are manifold and range from a very general antipathy against the rodent model system to well-founded arguments that highlight physiological variations between species. Newly proposed differences in genetic pathways that cause cancer in humans and mice invigorated the ongoing discussion about the legitimacy of the murine system to model the human disease. The present commentary intends to stimulate a debate on this subject by providing the background about new developments in animal modeling, by disputing suggested limitations of genetically engineered mice, and by discussing improvements but also ambiguous expectations on the authenticity of xenograft models to faithfully mimic the human disease
J. A. Potashkin
Full Text Available Most cases of Parkinson's disease (PD are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.
Madhu Devi* and Ramica Sharma
As described by the world health organization (WHO), depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective diso...
Full Text Available 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.
Ming Xu; Hongzhi Xu; Zhiyong Qin
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 ...
Kim, Sang-Woo; Kim, Kyoung-Shim; Solis, Chester D.; Lee, Myeong-Seop; Hyun, Byung-Hwa
Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic n...
3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea
Nordquist Rebecca E
Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to
Patel, Mitul; Rojavin, Yuri; Jamali, Amir A.; Wasielewski, Samantha J.; Salgado, Christopher J.
Osteomyelitis is an acute or chronic inflammatory process of the bone and its related structures secondary to an infection with pyogenic organisms. Because of the variety in disease presentations and pathophysiology of osteomyelitis, it is very difficult to evaluate in clinical studies. Therefore, animal models have been created for in vivo experimentation. A PubMed and OVID search was performed on March 31, 2008, using keywords osteomyelitis, animal model (rabbit, rat, mouse, avian, dog, she...
Archana M Navale
Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primi...
J. A. Potashkin; Blume, S. R.; Runkle, N. K.
Most cases of Parkinson's disease (PD) are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of t...
Neyt, J. G.; Buckwalter, J. A.; Carroll, N. C.
Understanding of the human musculoskeletal system and common clinical disorders of bones, joints and soft tissues has been enhanced by the use of experimental animal models. Articles reporting on the results of these biomedical experiments frequently include conclusions that are based on the assumption that the biology of the animal model is similar to that of a human being for the disease process under investigation. The purpose of this investigation was to study the criteria and the conside...
Warden, S. J.
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 po...
Turner A. Simon
There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep ar...
Jiang, Hai-Hong; Damaser, Margot S.
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 S...
Sidney D'MELLO, Stan FRANKLIN
Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework c...
Turner A. Simon
Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.
Crabbe, John C
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. PMID:27588527
Daunton, Nancy G.
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.
Archana M. Navale
Full Text Available Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primitive models. Although these models show good resemblance to the natural disease in humans, they were not capable of keeping pace with developing experimental therapeutics programs. It has therefore been necessary to take a further step towards artificiality, away from the clinical problem in the search for satisfactory testing method. From this step, the journey of artificially induced tumor models started. It is possible to induce cancer reproducibly in animals by exposing them to various agents and now, by transplanting tumor cells or tissue. The development of Genetically Engineered Animal models has provided a great help in knowing the disease. This article takes a review of present animal models used in anti-cancer drug discovery.
The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)
Bonde, Marianne; Botreau, R; Bracke, MBM;
One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfare...... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....
Campos, Alline C; Manoela V. Fogaca; Daniele C. Aguiar; Guimaraes, Francisco S.
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 mecha...
Han, Linda L.; Vasil Pani; Sandra Smole; Werner, Barbara G.; Xingtai Wang
Simple Summary We analyzed signs occurring among domestic and wild terrestrial animal species with raccoon rabies variant virus in Massachusetts, 1992–2010. While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals. Abstract We analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (RRV) in ...
Ellis, Emily A; Oakley, Todd H
One of the great mysteries of evolutionary biology is why closely related lineages accumulate species at different rates. Theory predicts that populations undergoing strong sexual selection will more quickly differentiate because of increased potential for genetic isolation [1-6]. Whether or not these population genetic processes translate to more species at macroevolutionary scales remains contentious . Here we show that lineages with bioluminescent courtship, almost certainly a sexually selected trait, have more species and faster rates of species accumulation than their non-luminous relatives. In each of ten distantly related animal lineages from insects, crustaceans, annelid worms, and fishes, we find more species in lineages with bioluminescent courtship compared to their sister groups. Furthermore, we find under a Yule model that lineages with bioluminescent courtship displays have significantly higher rates of species accumulation compared to a larger clade that includes them plus non-luminous relatives. In contrast, we do not find more species or higher rates in lineages that use bioluminescence for defense, a function presumably not under sexual selection. These results document an association between the origin of bioluminescent courtship and increased accumulation of species, supporting theory predicting sexual selection increases rates of speciation at macroevolutionary scales to influence global patterns of biodiversity. PMID:27345160
Barron, M.G.; Stehly, Guy R.; Hayton, W.L.
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.
Objective: To select the proper experimental animal model for research on prevention and treatment of hyperlipidemia. Method: Hyperlipidemia models of mouse, rat, golden hamster, guinea pig, rabbit, pigeon and quail often used in the last ten years were compared. Results: Golden hamster and guinea pig models are similar to human beings in lipid metabolism and have unique superiority in experimental study, while the models of rat, mouse, pigeon and quail have significant difference as compared...
Krishnan, Vaishnav; Nestler, Eric J.
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 ass...
Arends, Mark; White, Eric; Whitelaw, Christopher
In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.
Biessels, G J; Bril, V; Calcutt, N A;
NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The...
McCarthy, F P
Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.
Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.
Weingartl, Hana M; Berhane, Yohannes; Czub, Markus
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. PMID:19084436
Bourne, G. H.
The different types of primates which might be used as flight animals are surveyed, and the pros and cons of using them are discussed. Various factors suggest that the most desirable animals for space studies are the rhesus, pig-tailed, Java, and squirrel monkeys. The capuchin monkey has assets for certain types of space experimentation.
Previous work has established a relationship between knowledge and environmental concern. Different factors may contribute to this knowledge and animal-related leisure activities may also contribute to this knowledge. 390 participants in Leipzig, Germany were interviewed to assess their animal-related leisure activities, their demographic status…
Kingsley, S Manoj Kumar; Bhat, B Vishnu
Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis. PMID:27432263
Auvin, Stéphane; Pineda, Eduardo; Shin, Don; Gressens, Pierre; Mazarati, Andrey
When mimicking epileptic processes in a laboratory setting, it is important to understand the differences between experimental models of seizures and epilepsy. Because human epilepsy is defined by the appearance of multiple spontaneous recurrent seizures, the induction of a single acute seizure without recurrence does not constitute an adequate epilepsy model. Animal models of epilepsy might be useful for various tasks. They allow for the investigation of pathophysiological mechanisms of the ...
Sicard Kenneth M; Fisher Marc
Abstract 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.
Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a "barcode", has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. PMID:17226815
Reed, Danielle R
Food intake of humans is governed by the food's nutritional value and pleasing taste, but also by other factors such as food cost and availability, cultural imperatives, and social status. The biological determinants of human food intake are not easily parsed from these other factors, making them hard to study against the whirligig aspects of human life in a modern age. The study of animals provides a useful alternative. Humans have a history of studying animal food intake, for agricultural reasons (e.g., pigs and cows), and for personal reasons (e.g., dogs and cats), and these practical concerns have been joined with the appreciation that other models can teach us the principles of behavior, genetics, and nutrition. Thus there is a steady use of the traditional animal models in this type of research, as well as growth in the use of other systems such as worms and flies. Rats and mice occupy a special niche as animal models for two reasons; first, they share with humans a love of the same types of food, and second, they are the target of a number of well-developed genetic tools. The available genetic tools that make mice a popular model include a well-annotated genome (Mouse Build 37), profiles of RNA expression from many tissues, a diverse panel of inbred strains, and the ability to manipulate genes in the whole animal, including removing a gene only in specific tissues (e.g., Cre-lox system). Mice have been harnessed to find genotypes that contribute to sweet-liking, and other studies are underway to understand how genetic variation might at least partially explain other puzzles of human appetites. Animal models provide a way to study the genetic determinants of food selection with experimental rigor and therefore complement human genetics studies. PMID:19037208
Varga, Orsolya E.; Axel K. Hansen; Sandøe, Peter; Olsson, I Anna S
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 human condition it is intended to model, but no formal validation of models is applied. There is a stark contrast here with non-animal alternatives in toxicology and safety studies, for which an extensive validation is required. In the present paper...
Pattee, O.H.; Fellows, V.L.; Bounds, D.L.
Summary & conclusions: Multiple factors contribute to the decline of species. Habitat destruction is the primary factor that threatens species. affecting 73 % of endangered species. The second major factor causing species decline is the introduction of nonnative species. affecting 68% of endangered species. Pollution and overharvesting were identified as impacting, respectively, 38 and 15% of endangered species. Other factors affecting species decline include hybridization, competition, disease, and other interspecific interactions. Once a species is reduced to a remnant of its former population size and distribution, its vulnerability to catastrophic pollution events increases, frequently exceeding or replacing the factors responsible for the initial decline. Small, isolated populations are particularly vulnerable to catastrophic loss by an acute event. such as a chemical spill or pesticide application. However, when it comes to surviving a single disaster, widespread subpopulations of a species are far more resilient and ensure genetic survival. Hypothesizing theoretical concerns of potential factors that could affect an endangered species could predispose the scientific and political communities to jeopardizing threats. The user of recovery plans as a data source must be aware of the bias within the data set. These data should be used with the caveat that the source of information in recovery plans is not always based on scientific research and rigorous data collection. Over 58% of the information identifying species threats is based on estimates or personal communication. while only 42% is based on peer reviewed literature, academic research. or government reports. Many recovery plans were written when a species was initially listed in the 1970s or 1980s. Politics, human disturbance, and habitat demand issues evolve over a 20- to 30-year period. leaving much of the threats facing endangered species outdated and inadequate. These data are most valuable when used
Animal models for the study of erectile function monitoring the changes in intracavernous pressure(ICP)during penile erection was reviewed.The development of new modwls using small commercially-available experimen-tal animals,rats and mice,in the last edcade facilitated in vivo investigation of erectile physiology.The technique enabled to evaluate even subtle erectile responses by analyzing ICPand systemic blood pressure,Moreover,the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection.Also,more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICPstudies in rats and mice.
Tomomi Yamamoto-Fukuda; Haruo Takahashi; Takehiko Koji
Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have b...
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
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
Deponti, Daniela; Di Giancamillo, Alessia; Scotti, Celeste; Peretti, Giuseppe M; Martin, Ivan
The meniscus plays an important role in knee function and mechanics. Meniscal lesions, however, are common phenomena and this tissue is not able to achieve spontaneous successful repair, particularly in the inner avascular zone. Several animal models have been studied and proposed for testing different reparative approaches, as well as for studying regenerative methods aiming to restore the original shape and function of this structure. This review summarizes the gross anatomy, function, ultrastructure and biochemical composition of the knee meniscus in several animal models in comparison with the human meniscus. The relevance of the models is discussed from the point of view of basic research as well as of clinical translation for meniscal repair, substitution and regeneration. Finally, the advantages and disadvantages of each model for various research directions are critically discussed. PMID:23712959
Buurt, van G.; Debrot, A.O.
An overview of 72 invasive animals of the terrestrial and freshwater environments of the Dutch Caribbean, eleven of which are no longer present. All invasive animals that are principally agricultural pests and or animal and plant diseases (46 species) are excluded as these are discussed separately e
Yu, X.; Wang, J.; Kays, R.; Jansen, P.A.; Wang, T.; Huang, T.
Image sensors are increasingly being used in biodiversity monitoring, with each study generating many thousands or millions of pictures. Efficiently identifying the species captured by each image is a critical challenge for the advancement of this field. Here, we present an automated species identif
Sider, Krista L.; Blaser, Mark C.; Simmons, Craig A.
Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the u...
Haigwood, Nancy L.
Animal models for HIV research have been indispensible in fulfilling Koch’s postulate and in exploring issues of viral infectivity and pathogenesis, sequence divergence, route(s) of acquisition, tissue distribution and tropism, immunogenicity and protection capacity of vaccine candidates, escape from adaptive immunity, and more. Did they fail to predict the efficacy of T cell vaccines in humans? This article summarizes progress and status of models to inform and complement clinical work.
Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.
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 ...
Stables, Catherine L; Glasser, Rebecca L; Feldman, Eva L
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. PMID:23562143
Ewers, Robert M; Didham, Raphael K
Habitat fragmentation causes extinction of local animal populations by decreasing the amount of viable "core" habitat area and increasing edge effects. It is widely accepted that larger fragments make better nature reserves because core-dwelling species have a larger amount of suitable habitat. Nevertheless, fragments in real landscapes have complex, irregular shapes. We modeled the population sizes of species that have a representative range of preferences for or aversions to habitat edges at five spatial scales (within 10, 32, 100, 320, and 1000 m of an edge) in a nation-wide analysis of forest remnants in New Zealand. We hypothesized that the irregular shapes of fragments in real landscapes should generate statistically significant correlations between population density and fragment area, purely as a "geometric" effect of varying species responses to the distribution of edge habitat. Irregularly shaped fragments consistently reduced the population size of core-dwelling species by 10-100%, depending on the scale over which species responded to habitat edges. Moreover, core populations within individual fragments were spatially discontinuous, containing multiple, disjunct populations that inhabited small spatial areas and had reduced population size. The geometric effect was highly nonlinear and depended on the range of fragment sizes sampled and the scale at which species responded to habitat edges. Fragment shape played a strong role in determining population size in fragmented landscapes; thus, habitat restoration efforts may be more effective if they focus on connecting disjunct cores rather than isolated fragments. PMID:17650243
Jonathan Mark Warawa
Full Text Available 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.
Full Text Available Abstract Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy. Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities.
Full Text Available Latest trends in understanding of respiratory diseases in human beings can be derived from thorough clinical studies of these diseases occurring in man, but conducting such studies in man is difficult in terms of experimental manipulation. In the last 2 decades, various types of experimental respiratory disease models has been developed and utilized by investigators, which have contributed a lot to the understanding of respiratory diseases in man, but only little investigation has been done on the naturally occurring pulmonary diseases of animals as potential models which could have added to our knowledge. There are certain selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma.
Alline C. Campos
Full Text Available 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.
Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.
Rene Kizek*; Libuse Trnkova; Jaromir Hubalek; Jiri Pikula; Miroslava Beklova; Vojtech Adam
Metallothioneins play a key role in maintaining homeostasis of essential metals and in protecting of cells against metal toxicity as well as oxidative damaging. Excepting humans, blood levels of metallothionein have not yet been reported from any animal species. Blood plasma samples of 9 animal species were analysed by the adsorptive transfer stripping technique to obtain species specific voltammograms. Quite distinct records were obtained from the Takin (Budorcas taxicolor), while other inte...
de Jong, Johannes W; Vanderschuren, Louk J M J; Adan, Roger A H
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
Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I
The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894
Full Text Available Ludmyla Kandratavicius,1 Priscila Alves Balista,1 Cleiton Lopes-Aguiar,1 Rafael Naime Ruggiero,1 Eduardo Henrique Umeoka,2 Norberto Garcia-Cairasco,2 Lezio Soares Bueno-Junior,1 Joao Pereira Leite11Department of Neurosciences and Behavior, 2Department of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, BrazilAbstract: Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research.Keywords: epilepsy, animal model, pilocarpine, kindling, neurodevelopment
Cleopatra S. Planeta
Full Text Available Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.
Torres, Arnau; Gómez, Javier
The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications. The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...
... appropriate protective action. (v) Assisting recovery teams, as appropriate, in preparing species recovery... 7 Agriculture 6 2010-01-01 2010-01-01 false Rare, threatened, and endangered species of plants and... Related Environmental Concerns § 650.22 Rare, threatened, and endangered species of plants and animals....
Al-Awar, Amin; Kupai, Krisztina; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba
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. PMID:27595114
Seyam, Raouf M.; Said A Kattan; Assad, Lina W.; Raafat M El-Sayed; Falah H Almohanna
Context: Penile allotransplantation might be a viable option for patients who need penile reconstruction. Aims: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. Settings and Design: Experimental animal study. Materials and Methods: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification o...
Lixin Kan; Kessler, John A.
Heterotopic ossification (HO) is the formation of marrow-containing bone outside of the normal skeleton. Acquired HO following traumatic events is a common and costly clinical complication. In contrast, hereditary HO is rarer, progressive, and life-threatening. Substantial effort has been directed towards understanding the mechanisms underlying HO and finding efficient treatments. However, one crucial limiting factor has been the lack of relevant animal models. This article reviews the major ...
Harding, John; Roberts, R. Michael; Mirochnitchenko, Oleg
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 nov...
Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas
This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now,...
Warawa, Jonathan Mark
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...
Tamar Farfel-Becker; Vitner, Einat B.; Futerman, Anthony H.
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display sympt...
Xue Cai; McGinnis, James F.
Diabetic retinopathy (DR) is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment a...
Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (chickenpox followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles. HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella and Zostavax® (for HZ. Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.
Archer, Trevor; Kostrzewa, Richard M
Over the past 60 years, a large number of selective neurotoxins were discovered and developed, making it possible to animal-model a broad range of human neuropsychiatric and neurodevelopmental disorders. In this paper, we highlight those neurotoxins that are most commonly used as neuroteratologic agents, to either produce lifelong destruction of neurons of a particular phenotype, or a group of neurons linked by a specific class of transporter proteins (i.e., dopamine transporter) or body of receptors for a specific neurotransmitter (i.e., NMDA class of glutamate receptors). Actions of a range of neurotoxins are described: 6-hydroxydopamine (6-OHDA), 6-hydroxydopa, DSP-4, MPTP, methamphetamine, IgG-saporin, domoate, NMDA receptor antagonists, and valproate. Their neuroteratologic features are outlined, as well as those of nerve growth factor, epidermal growth factor, and that of stress. The value of each of these neurotoxins in animal modeling of human neurologic, neurodegenerative, and neuropsychiatric disorders is discussed in terms of the respective value as well as limitations of the derived animal model. Neuroteratologic agents have proven to be of immense importance for understanding how associated neural systems in human neural disorders may be better targeted by new therapeutic agents. PMID:26857462
Matteo Di Segni
Full Text Available 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.
Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella
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. PMID:25340369
Diaz Brinton, Roberta
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 co...
Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima
Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders. PMID:25760215
Planeta, Cleopatra S.
Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overvi...
LIU Shi-guang; WANG Zhang-ye; GONG Zheng; CHEN Fei-fei; PENG Qun-sheng
Realistic modeling and rendering of dynamic tornado scene is recognized as a challenging task for researchers of computer graphics. In this paper a new physically based method for simulating and animating tornado scene is presented. We first propose a Two-Fluid model based on the physical theory of tornado, then we simulate the flow of tornado and its interaction with surrounding objects such as debris, etc. Taking the scattering and absorption of light by the participating media into account, the illumination effects of the tornado scene can be generated realistically. With the support of graphics hardware, various kinds of dynamic tornado scenes can be rendered at interactive rates.
Panfil, Amanda R.; Al-Saleem, Jacob J; Green, Patrick L
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 examinin...
Maxim V. Vinarski
Lymnaea stagnalis (L., 1758) is among the most widespread and well-studied species of freshwater Mollusca of the northern hemisphere. It is also notoriously known for its huge conchological variability. The history of scientific exploration of this species may be traced back to the end of the 16th century (Ulisse Aldrovandi in Renaissance Italy) and, thus, L. stagnalis has been chosen as a proper model taxon to demonstrate how changes in theoretical foundations and methodology of animal taxon...
Animal models and endophenotypes of mental disorders are regarded as preclinical heuristic approaches aiming at understanding the etiopathogenesis of these diseases, and at developing drug treatment strategies. A frequently used translational model of sensorimotor gating and its deficits in some neuropsychiatric disorders is prepulse inhibition (PPI) of startle. PPI is reduced in schizophrenia patients, but the exact relationship between symptoms and reduced PPI is still unclear. Recent findings suggest that the levels of PPI in humans and animals may be predictive of certain cognitive functions. Hence, this simple measure of reflex suppression may be of use for clinical research. PPI is the reduction of the acoustic startle response that occurs when a weak prestimulus is presented shortly prior to a startling noise pulse. It is considered a measure of sensorimotor gating and is regulated by a cortico-limbic striato-pallidal circuit. However, PPI does not only occur in the domain of startle. PPI of alpha, gamma, and theta oscillations at frontal and central locations has been found, suggesting a relationship between PPI and cognitive processes. In fact, levels of PPI in healthy subjects and in animals predict their performance in cognitive tasks mainly mediated by the frontal cortex. Taken together, PPI might reflect a more general filtering performance leading to gating of intrusive sensory, motor, and cognitive input, thereby improving cognitive function. Hence, PPI might be used in clinical settings to predict the impact of drugs or psychotherapy on cognitive performance in neuropsychiatric patients. PMID:24053035
Dehling, D.M.; Hof, C.; Brandle, M.;
species richness. We tested whether habitat availability can account for the differences in species richness patterns between European lentic and lotic freshwater animals. Location Europe. Methods We compiled occurrence data of 1959 lentic and 2445 lotic species as well as data on the amount of lentic and......Aim In Europe, the relationships between species richness and latitude differ for lentic (standing water) and lotic (running water) species. Freshwater animals are highly dependent on suitable habitat, and thus the distribution of available habitat should strongly influence large-scale patterns of...... latitude. Main conclusions Habitat availability and diversity are poor predictors of species richness of the European freshwater fauna across large scales. Our results indicate that the distributions of European freshwater animals are probably not in equilibrium and may still be influenced by history...
O'Neil, Michael F; Moore, Nicholas A
Simple tests for antidepressant-like activity, such as 5-HTP-induced syndrome or reserpine-induced hypomotility, are often mechanism-based tests, pharmacologically specific for certain known classes of therapeutically successful antidepressant agents. Many of these behavioural assays have been superseded by neurochemical techniques such as in vivo microdialysis. In contrast to these mechanistic-based models, investigators have also endeavoured to reproduce in the laboratory, factors that are believed to precipitate depression in people. It is a strong assumption in this approach that depression is a response to stress. This strategy profiles the consequences of chronic stress particularly psychosocial stress or early life events, in order to reproduce in animals the behavioural signs and pathologies associated with depression. The advances in the social psychological, clinical pathological and new areas such as neuroimaging research offer the possibility of establishing more sophisticated models for depression in animals with a broader range of biomarkers from the immunological and endocrinological to neurochemical and behavioural. Combining these novel insights with more traditional tests of depression may not only increase our understanding of the neurobiology of depression but also afford more precise and predictive preclinical models of depression. The responsiveness of different strains or genetically modified animals to stress is likely to be a key area of study. Furthermore we must look to individual differences in subjects, even within the same strain, to more fully understand why some individuals show pathological responses to stress whereas others appear unaffected. Conversely in validating our models using currently available treatments we must include the concept of non-responders so as not to disregard models that may extend therapeutic possibilities in these patients. PMID:12766928
Koob, G F
Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving. PMID:11002904
Full Text Available In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail
Blanchet, Pierre J; Parent, Marie-Thérèse; Rompré, Pierre H; Lévesque, Daniel
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
Blanchet Pierre J
Full Text Available Abstract 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.
Ruzauskas, Modestas; Couto, Natacha; Kerziene, Sigita; Siugzdiniene, Rita; Klimiene, Irena; Virgailis, Marius; Pomba, Constança
Background The bacterial genus Staphylococcus consists of many species that causes infections in pet animals. Antimicrobial resistant staphylococci cause infections that are difficult to treat and they are important from the point of one health perspective. The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus (MRS) species, including methicillin-resistant S. aureus (MRSA) in diseased pet animals (Group A) and kennel dogs (Group B) in Lithuania and to c...
Cláudia L Vitral; Marcelo A Pinto; Lewis-Ximenez, Lia L.; Yuri E Khudyakov; Débora R dos Santos; Ana Maria C. Gaspar
Serological evidence of hepatitis E virus infection (HEV) has been observed in both humans and different animal species living in non-endemic areas, suggesting that animals could be important reservoir for virus transmission to man. Antibodies to HEV have been detected in some Brazilian population groups. Nevertheless, sporadic cases of acute HEV infection have never been reported. We collected 271 serum samples from several domestic animals and also from pig handlers from Southeast of Brazil...
Iyer, Balaji V. S.; Arya, Gaurav
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.
Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas
This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...... disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of...
Delgado, M R; Olsson, A; Phelps, E A
A goal of fear and anxiety research is to understand how to treat the potentially devastating effects of anxiety disorders in humans. Much of this research utilizes classical fear conditioning, a simple paradigm that has been extensively investigated in animals, helping outline a brain circuitry thought to be responsible for the acquisition, expression and extinction of fear. The findings from non-human animal research have more recently been substantiated and extended in humans, using neuropsychological and neuroimaging methodologies. Research across species concur that the neural correlates of fear conditioning include involvement of the amygdala during all stages of fear learning, and prefrontal areas during the extinction phase. This manuscript reviews how animal models of fear are translated to human behavior, and how some fears are more easily acquired in humans (i.e., social-cultural). Finally, using the knowledge provided by a rich animal literature, we attempt to extend these findings to human models targeted to helping facilitate extinction or abolishment of fears, a trademark of anxiety disorders, by discussing efficacy in modulating the brain circuitry involved in fear conditioning via pharmacological treatments or emotion regulation cognitive strategies. PMID:16472906
Ward, Marsha D W; Selgrade, Maryjane K
Protein induced respiratory hypersensitivity, particularly atopic disease in general, and allergic asthma in particular, has increased dramatically over the last several decades in the US and other industrialized nations as a result of ill-defined changes in living conditions in modern western society. In addition, work-related asthma has become the most frequently diagnosed occupational respiratory illness. Animal models have demonstrated great utility in developing an understanding of the etiology and mechanisms of many diseases. A few models been developed as predictive models to identify a protein as an allergen or to characterize its potency. Here we describe animal models that have been used to investigate and identify protein respiratory sensitizers. In addition to prototypical experimental design, methods for exposure route, sample collection, and endpoint assessment are described. Some of the most relevant endpoints in assessing the potential for a given protein to induce atopic or allergic asthma respiratory hypersensitivity are the development of cytotropic antibodies (IgE, IgG1), eosinophil influx into the lung, and airway hyperresponsiveness to the sensitizing protein and/or to non-antigenic stimuli (Mch). The utility of technologies such as PCR and multiplexing assay systems is also described. These models and methods have been used to elucidate the potential for protein sources to induce allergy, identify environmental conditions (pollutants) to impact allergy responsiveness, and establish safe exposure limits. As an example, data are presented from an experiment designed to compare the allergenicity of a fungal biopesticide Metarhizium anisopliae (MACA) crude extract with the one of its components, conidia (CON) extract. PMID:17161304
Ponnappa, B C; Rubin, E
Researchers have developed numerous animal models to investigate the development of various alcohol-related diseases. Such models have provided insights into the mechanism through which alcohol can induce liver damage. Animal models also have helped researchers explore the mechanisms by which both short-term (e.g., binge) and long-term drinking can interfere with the function of the heart, a condition referred to as alcoholic cardiomyopathy. Furthermore, animal models have provided substantial information on the causes of fetal alcohol syndrome. Such models have demonstrated that exposure to alcohol during gestation can lead to prenatal and postnatal growth retardation, characteristic facial malformations, immune system deficiencies, and alterations in the central nervous system. PMID:11199283
Muhammad Nazrul Somchit
Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.
McPeek, Mark A; Brown, Jonathan M
Animal taxa show remarkable variability in species richness across phylogenetic groups. Most explanations for this disparity postulate that taxa with more species have phenotypes or ecologies that cause higher diversification rates (i.e., higher speciation rates or lower extinction rates). Here we show that clade longevity, and not diversification rate, has primarily shaped patterns of species richness across major animal clades: more diverse taxa are older and thus have had more time to accumulate species. Diversification rates calculated from 163 species-level molecular phylogenies were highly consistent within and among three major animal phyla (Arthropoda, Chordata, Mollusca) and did not correlate with species richness. Clades with higher estimated diversification rates were younger, but species numbers increased with increasing clade age. A fossil-based data set also revealed a strong, positive relationship between total extant species richness and crown group age across the orders of insects and vertebrates. These findings do not negate the importance of ecology or phenotype in influencing diversification rates, but they do show that clade longevity is the dominant signal in major animal biodiversity patterns. Thus, some key innovations may have acted through fostering clade longevity and not by heightening diversification rate. PMID:17427118
Nates, Juliana; Campos, Claudia; Lindemann-Matthies, Petra
Exotic species seriously affect local biodiversity in Argentina. This article investigates how students in San Juan province perceive native and exotic species. With the help of a written questionnaire, 865 students (9-17 years old) were asked to name the plant and animal they liked most, disliked most, and perceived as most useful, and to name…
Linda L. Han
Full Text Available We analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (RRV in Massachusetts, 1992–2010. The clinical sign of aggression was significantly associated with rabid stray cats (odds ratio, OR = 2.3 and RRV affected major wild terrestrial animal species individually, which included raccoons (OR = 2.8, skunks (OR = 8.0, gray foxes (OR = 21.3, red foxes (OR = 10.4, woodchucks (OR = 4.7 and coyotes (OR = 27.6. While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals. Pets reported with multiple clinical signs had significantly higher rabies positive testing result than those reported with single clinical sign (p < 0.001. The result suggested the importance of avoiding aggressive terrestrial wild animals and giving additional attention to pets with multiple clinical signs.
Million, M; Angelakis, E; Paul, M.; Armougom, Fabrice; Leibovici, L; Raoult, Didier
Background: Obesity is associated with alteration of the gut microbiota. In order to clarify the effect of Lactobacillus-containing probiotics (LCP) on weight we performed a meta-analysis of clinical studies and experimental models. We intended to assess effects by Lactobacillus species. Methods: A broad search with no date or language restriction was performed. We included randomized controlled trials (RCTs) and comparative clinical studies in humans and animals or experimental models assess...
D. SAVINI; A. OCCHIPINTI AMBROGI; Marchini, A; Tricarico, E; GHERARDI F.; Olenin, S.; Gollasch, S.
The information extracted from IMPASSE, DAISIE, Fish-Base, and FAO-DIAS inventories of alien species were used to draw a list of the 27 most utilized animal alien species for aquaculture and related activities (e.g. stocking, sport fishing, ornamental purposes) in Europe. Three variables have been considered to assess their negative ecological impacts when these species escape from aquaculture facilities: (i) their distribution across Europe (including non-EU Member States); (ii) evidence of ...
Cenci, M Angela; Whishaw, Ian Q; Schallert, Timothy
Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates. PMID:12094213
Manuel Eduardo Góngora; Cristina Vargas-Irwin; Lady Andrea Polanco
The aim of this paper is to present a review of commonly used animal models tostudy anxiety, looking to make a presentation of three instruments used in thelaboratory. It describes the importance of using animal models for understandinghuman behavior; there are two groups of animal models and the most representativetests for each of these.
Cai, Bin; Wang, Ning
Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009. PMID:26463926
Aghdassi Alexander A
Full Text Available Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.
Aghdassi, Alexander A; Mayerle, Julia; Christochowitz, Sandra; Weiss, Frank U; Sendler, Matthias; Lerch, Markus M
Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269
Full Text Available Huntington's disease (HD is an inherited autosomal, progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea, cognitive impairments and psychiatric disturbances. HD is caused by an abnormal expansion of a CAG region located in exon 1 of the gene encoding the huntingtin protein (Htt and is the causative factor in the pathogenesis of HD Animal models of HD have provided insight into disease pathology and the outcomes of thera- peutic strategies. Earlier studies of HD most often used toxin-induced models to study mitochondrial impairment and excitotoxicity-induced cell death, which are both mechanisms of degeneration seen in the HD brain. These models, based on 3-nitropropionic acid and quinolinic acid, respectively, are still often used in HD studies. The discovery in 1993 of the huntingtin mutation led to the creation of newer models that incorporate a similar genetic defect. These models, which include transgenic and knock-in rodents, are more representative of the HD progression and pathology. An even more recent model that uses a ovine transgenic model (sheep model,fly models ,cell cultures models for better understanding of gene mutation in and in mammalian and nonhuman primates, as it is difficult to produce genetic models in these species. This article examines the aforementioned models and describes their use in HD research, including aspects of the creation, de- livery, pathology, and tested therapies for each model.
Mikkelsen, Jakob H; Steffensen, Lasse B; Oxvig, Claus
formalin-fixed and paraffin-embedded tissue. For increased sensitivity, affinity maturation to sub-nanomolar affinity was then carried out. The resulting recombinant antibody, PAC1-D8-mIgG2a, detects PAPP-A specifically and sensitively in human tissue. In addition, this antibody allows detection of PAPP...... normal physiology and under different pathological conditions. However, antibodies for the detection of PAPP-A in non-human tissues have been lacking, although needed for use with several animal models which are currently being developed. To develop a monoclonal antibody suitable for the......-A in non-human species. We demonstrate its usefulness for the visualization of PAPP-A in murine and porcine tissues....
Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies
Full Text Available
The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.
Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.
The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.
This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.
Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models
Full Text Available The study objective was to assess the floristic composition of pastures for wild animals (fallow deer, Manchurian deer and mouflons at Przytoczno, pastures for horses at Białka, and cow pastures belonging to the Land Community in Tarnogóra. We analyzed the floristic composition of the pastures under study in the growing seasons of 2011 and 2012, carried out 32 phytosociological relevés in the wild animal pastures, 32 in the horse pastures, and 38 in the cow pastures, using the Braun-Blanquet method. We determined the species diversity of the pastures based on the percentage share of species from the botanical families distinguished, the total number of species, and the Shannon–Wiener and Simpson diversity index. Our floristic surveys indicated that the greatest species diversity occurred in the horse pastures, while it was lower in the wild animal and cow pastures. The Shannon–Wiener diversity index for the sward of the pastures grazed by horses was higher (H' = 5.04 than for those grazed by wild animals (H' = 4.32 and cows (H' = 3.53. The Simpson index of species diversity in a community was higher for the pastures grazed by horses (S = 0.96 than for those grazed by wild animals (S = 0.95 and cows (S = 0.90.
Suzuki, Takuya; Ichihara, Masako; Hyodo, Kenji; Yamamoto, Eiichi; Ishida, Tatsuhiro; Kiwada, Hiroshi; Kikuchi, Hiroshi; Ishihara, Hiroshi
We recently demonstrated that Doxil loses its long-circulating properties when injected repeatedly at doses below 2 mg/m(2) in dogs. In studies using other animal species, PEGylated liposomal doxorubicin has been reported not to induce the accelerated blood clearance (ABC) phenomenon. We investigated the issue of whether Doxil can elicit the ABC phenomenon in several species. In minipigs, the ABC phenomenon was induced at 2 mg/m(2). In other animal species, the ABC phenomenon was not observed at higher doses (>2 mg/m(2)), but was observed at much lower doses (0.2 mg/m(2)). The pharmacokinetic profile of a second dose of Doxil reflected the circulating anti-PEG IgM level induced by the first dose. The ABC phenomenon was not observed at the clinically recommended DXR dose (20 mg/m(2)) in any animal species. These results indicate that Doxil can cause the ABC phenomenon in all animals tested, the extent of induction was dependent on the first dose of Doxil, and a higher Doxil dose lessened the ABC phenomenon. The current study results suggest that a careful study design including selection of animal species is important for preclinical studies using PEGylated liposomal formulations even if they contain anticancer drugs that suppress the host immune response. PMID:25280884
Martinez, M; Mahmood, I; Hunter, R P
Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. However, it is important to appreciate the mathematical underpinnings of this scaling procedure when using it to predict pharmacokinetic parameter values across animal species. When cautiously applied, allometry can be a tool for estimating clearance in veterinary species for the purpose of dosage selection. It is particularly valuable during the selection of dosages in large zoo animal species, such as elephants, large cats and camels, for which pharmacokinetic data are scant. In Part I, allometric predictions of clearance in large animal species were found to pose substantially greater risks of inaccuracies when compared with that observed for humans. In this report, we examine the factors influencing the accuracy of our clearance estimates from the perspective of the relationship between prediction error and such variables as the distribution of body weight values used in the regression analysis, the influence of a particular observation on the clearance estimate, and the 'goodness of fit' (R(2)) of the regression line. Ultimately, these considerations are used to generate recommendations regarding the data to be included in the allometric prediction of clearance in large animal species. PMID:16958788
Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution
DONG Ke; ZHONG Xianghao; LIU Shuzhen
It is of profound theoretical and practical significance to study endangerment status of rare species in Tibet. Index system is firstly set down for quantitative assessment of rare animal and plant species, then endangerment degree of wildlife under special state protection are calculated, which is expressed by value E. The results reveal that Yunnan snub-nosed monkey (Rhinopithecus bieti), Himalayan tahr (Hemitragus jemlahicus) and Gigantic Cypress (Cupressus gigantea) have the highest E respectively in animals and plants. According to value E, all species are categorized into 4 ranks: critically endangered(0.6-0.8), endangered (0.4-0.6), vulnerable (0.2-0.4) and lower risk (E≤ 0.2). By comparison of the first five animals and plants of the highest E, each sub-ecozone bears a distinct identity.
Granton A. Jindal
Full Text Available RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.
Jindal, Granton A; Goyal, Yogesh; Burdine, Rebecca D; Rauen, Katherine A; Shvartsman, Stanislav Y
RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births) motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment. PMID:26203125
Finet, J. Emanuel; Rosenbaum, David S.; Donahue, J. Kevin
Animal models of atrial fibrillation have taught us about mechanisms of this common disease. A variety of animal models exist, including models of lone atrial fibrillation and models of atrial fibrillation in the setting of heart failure, aging or pericardial inflammation. This chapter reviews these various models.
This study sought to extend the niche model of Spartina anglica to other salt marsh species, and to include tidal submergence in the models. The method used and preliminary data analysis are described. Tidal level and submergence niche models are examined, and niche width, niche overlap and species interaction are considered. Tidal level models and submergence niche models are compared for the 5 most common species. (UK)
Gress, J; da Silva, E B; de Oliveira, L M; Zhao, Di; Anderson, G; Heard, D; Stuchal, L D; Ma, L Q
Animal enclosures are often constructed from wood treated with the pesticide chromated copper arsenate (CCA), which leaches arsenic (As) into adjacent soil during normal weathering. This study evaluated potential pathways of As exposure in 25 species of zoo animals living in CCA-wood enclosures. We analyzed As speciation in complete animal foods, dislodgeable As from CCA-wood, and As levels in enclosure soils, as well as As levels in biomarkers of 9 species of crocodilians (eggs), 4 species of birds (feathers), 1 primate species (hair), and 1 porcupine species (quills). Elevated soil As in samples from 17 enclosures was observed at 1.0-110mg/kg, and enclosures housing threatened and endangered species had As levels higher than USEPA's risk-based Eco-SSL for birds and mammals of 43 and 46mg/kg. Wipe samples of CCA-wood on which primates sit had dislodgeable As residues of 4.6-111μg/100cm(2), typical of unsealed CCA-wood. Inorganic As doses from animal foods were estimated at 0.22-7.8μg/kg bw/d. Some As levels in bird feathers and crocodilian eggs were higher than prior studies on wild species. However, hair from marmosets had 6.37mg/kg As, 30-fold greater than the reference value, possibly due to their inability to methylate inorganic As. Our data suggested that elevated As in soils and dislodgeable As from CCA-wood could be important sources of As exposure for zoo animals. PMID:26897404
Bacigaluppi, Marco; Comi, Giancarlo; Dirk M Hermann
Animal models of stroke provide an essential tool for the understanding of the complex cellular and molecular pathophysiology of stroke and for testing novel recanalyzing, neuroprotective, neuroregenerative or anti- inflammatory drugs in pre- clinical setting. Since the first description of the distal occlusion of the middle cerebral artery (MCA) in rats, different techniques and methods to induce focal and global ischemia of the brains have been developed and optimized. The different models,...
Jeffery L. Larkin
Full Text Available A recent model of Florida panther (Puma concolor coryi habitat erred in arbitrarily creating buffers around radio locations collected during daylight hours on the assumption that study animals were only at rest during these times. The buffers generated by this method likely cause an overestimation of the amounts and kinds of habitats that are used by the panther. This, and other errors, could lead to the impression that unfragmented forest cover is unimportant to panther conservation, and could encourage inaccurate characterizations of panther habitat. Previous 24-hour monitoring of activity and activity readings made during routine telemetry flights indicate that high levels of activity occur in the early morning hours. Literature on the behavior of the species does not support the creation of large buffers around telemetry locations to compensate for the lack of nighttime telemetry data. A thorough examination of ongoing studies that use global positioning systems may help calibrate future Florida panther habitat models.
Full Text Available Abstract 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.
Quite a substantial number of human disorders have been associated with a primary or a secondary impairment of one or several of the dopaminergic pathways. Among disorders associated with a primary impairment of dopaminergic transmission are Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, and possibly schizophrenia. Diseases of secondary dopamine dysfunction are chiefly represented by Huntington's disease in which dopaminergic transmission is being interrupted by progressive loss of the striatal neurons bearing the postsynaptic D1- and D2-dopamine receptors. Central dopaminergic systems have anatomical as well as organizational properties that render them unique by comparison to other neurotransmission systems, making them able to play a pivotal role in the modulation of various important brain functions such as locomotor activity, attention, and some cognitive abilities. These properties of dopamine neurons have obviously several implications in the clinical expression of human disorders involving dopamine neuron dysfunction. In addition, they can greatly influence the clinical/behavioral consequences of experimental lesions in animal models of dopamine dysfunctions
Full Text Available Varicocele is characterized by abnormal tortuosity and dilation of the veins of the pampiniform plexus within the spermatic cord. Although several reports show the mechanisms by which the varicocele exerts its infertility impact, the exact pathophysiology for varicocele-induced inflammation and its relationship with testicular endocrine disruption remain largely unknown. This review article will update previous findings by discussing the pathophysiology of long term-induced varicocele in rats. Testicular endocrine disruption in experimentally-induced varicocele, new findings related to biochemical alterations in germinal epithelium, and sperm cells apoptosis are highlighted. Recent observations show that varicocele down-regulates first and second maturation divisions, results in Leydig and Sertoli cell inflammation, and increases immune cell infiltration in the testes of the rat as an animal model. Ultimately, previous findings of our laboratory have revealed that varicocele decreased sperm motility, viability and severe DNA damage. Damage in sperm significantly lowers the animal’s fertility potential. Varicocele not only exerts its pathologic impact by lowering the testicular antioxidant capacity but it also down-regulates first and second maturation divisions by exerting biochemical alterations such as reducing the intracytoplasmic carbohydrate ratio in germinal epithelium.
Jones, A D
This paper examines the available experimental and theoretical results describing deposition and clearance of mineral fibres inhaled by animals and humans in order to define the limits which these mechanisms impose on the relevance of animal experiments in the assessment of potential human health risks. Direct experimental data for deposition of spherical particles are extended by examination of the physical processes and by some limited experimental data for fibres. This shows that alveolar deposition efficiency (in rat and in man) is sufficiently similar for particles and fibres with aerodynamic diameters less that 5 microns for rats to be a relevant model for airborne dusts in this size range. Inter-species differences in mechanical clearance are substantial, with clearance being faster in the rat than in man, and this is a factor which should be considered in interpreting animal toxicity studies. The durability of fibres in the biochemical conditions of the lung may be more important over the longer lifespan of humans. PMID:8317856
Stei, Marta M.; Loeffler, Karin U.; Holz, Frank G.; Herwig, Martina C.
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 intraocul...
Salles, Jean Pierre
Hypophosphatasia (HPP) is due to mutations of the tissue non-specific alkaline phosphatase (TNAP) gene expressed in the liver, kidney, and bone. TNAP substrates include inorganic pyrophosphate cleaved into inorganic phosphate (Pi) in bone, pyridoxal-5'-phosphate (PLP), the circulating form of vitamin B6, and phosphoethanolamine (PEA). As an autosomal recessive or dominant disease, HPP results in a range of clinical forms. Its hallmarks are low alkaline phosphatase (AP) and elevated PLP and PEA levels. Perinatal HPP may cause early death with respiratory insufficiency and hypomineralization resulting in deformed limbs and sometimes near-absence of bones and skull. Infantile HPP is diagnosed before 6 months of life. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency in the brain indicate poor prognosis. Craniosynostosis is frequent. Unlike in other forms of rickets, calcium and phosphorus are not decreased, resulting in hypercalciuria and nephrocalcinosis. Hypercalcemic crisis may occur. Failure to thrive and growth retardation are concerns. In infantile and adult forms of HPP, non-traumatic fractures may be the prominent manifestation, with otherwise unexplained chronic pain. Progressive myopathy has been described. Dental manifestations with early loss of teeth are usual in HPP and in a specific form, odontohypophosphatasia. HPP has been studied in knock-out mice models which mimic its severe form. Animal models have made a major contribution to the development of an original enzyme therapy for human infantile HPP, which is however essentially targeted at mineralized tissues. Better knowledge of its extraskeletal manifestations, including pain and neurological symptoms, is therefore required. PMID:26219704
Phipps, Helen W
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). PMID:27604713
Brabander, H.F. de; Poelmans, S.; Schilt, R.; Stephany, R.W.; Bizec, B. le; Draisci, R.; Sterk, S.S.; Ginkel, L.A. van; Courtheyn, D.; Hoof, N. van; Macrì, A.; Wasch, K. de
The review summarizes current knowledge on the possible illegal use of the anabolic steroid boldenone. The presence of boldenone and metabolites in different animal species and the possibility of the occurrence of endogenous boldenone and metabolites is assessed, as are the methods of analysis used
Silva, Teane M. A.; Erica A Costa; Tatiane A. Paixão; Renée M. Tsolis; Santos, Renato L
Brucellosis is a chronic infectious disease caused by Brucella spp., a Gram-negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated...
Darine Froy N. Mabunga; Gonzales, Edson Luck T.; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young
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 environmenta...
Neto, Eraldo Medeiros Costa
This article deals with the use of animals as medicinal resources in Bahia State, Northeastern Brazil. The data come from a processional evaluation of academic performance, since it was an exercise requested by the professor of the discipline Ethnobiology (2007.2 semester) to the students of the course Bahia State Teachers' Undergraduation of Feira de Santana State University. They were asked to make a brief survey, in their respective cities, on the use of animals as medicines. Forty-one students, from 21 cities of the country of Bahia State, have participated with data. A total of 95 animals (common names) were recorded, from which 17 are new additions to the list of medicinal animal species already published. The recording of the use of animals as folk medicines in the state of Bahia provides a significant contribution to the phenomenon of zootherapy, because it opens a space to debate about conservation biology, health public policies, sustainable management of natural resources, bioprospection, and patent. It is necessary to carry out more ethnozoological studies both to comprehend the true importance of zootherapy to the traditional communities and to develop some strategies of sustainable management and use of animal species, especially for those under risk of extinction. PMID:21503516
Roos, de, B.; Sawyer, J K; Katan, M.B.; Rudel, L L
Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys,...