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  1. Estimates of Genetic Parameters of Production Traits for Khuzestan Buffaloes of Iran using Repeated-Records Animal Model

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    Maryam Baharizadeh

    2012-10-01

    Full Text Available Buffalo milk yield records were obtained from monthly records of the Animal Breeding Organization of Iran from 1992 to 2009 in 33 herds raised in the Khuzestan province. Variance components, heritability and repeatability were estimated for milk yield, fat yield, fat percentage, protein yield and protein percentage. These estimates were carried out through single trait animal model using DFREML program. Herd-year-season was considered as fixed effect in the model. For milk production traits, age at calving was fitted as a covariate. The additive genetic and permanent environmental effects were also included in the model. The mean values (±SD for milk yield, fat yield, fat percentage, protein yield and protein percentage were 2285.08±762.47 kg, 144.35±54.86 kg, 6.25±0.90%, 97.30±26.73 kg and 4.19±0.27%, respectively. The heritability (±SE of milk yield, fat yield, fat percentage, protein yield and protein percentage were 0.093±0.08, 0.054±0.06, 0.043±0.05, 0.093±0.16 and zero, respectively. These estimates for repeatability were 0.272, 0.132, 0.043, 0.674 and 0.0002, respectively. Lower values of genetic parameter estimates require more data and reliable pedigree records.

  2. Animal models.

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    Walker, Ellen A

    2010-01-01

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

  3. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

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

  4. Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

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    Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

    2015-06-01

    Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

  5. Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

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    Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

    2014-06-01

    A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014.

  6. Accumulation of radioactivity after repeated infusion of 3H-adrenaline and 3H-noradrenaline in the rat as a model animal.

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    Lepschy, M; Filip, T; Palme, R G

    2014-10-01

    Besides enzymatic inactivation, catecholamines bind non-enzymatically and irreversible to proteins. The physiological impact of these catecholamine adducts is still unclear. We therefore collected basic data about the distribution of catecholamine adducts in the rat after repeated intravenous administration of (3)H-adrenaline and (3)H-noradrenaline. In all animals radioactivity in blood increased until the last injection on Day 7 and decreased then slowly close to background values (plasma) or remained higher (erythrocytes). In all sampled tissues radioactivity could be found, but only in hair high amounts remained present even after 3 weeks. Half-life of rat serum albumin loaded with (3)H-adrenaline or (3)H-noradrenaline was not altered. This study provides basic knowledge about the distribution of catecholamines or their adducts, but physiological effects could not be demonstrated. However, for the first time deposition and accumulation of catecholamines (adducts) in the hair could be proven, suggesting that hair might be used for evaluating long term stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Animal models of dementia

    DEFF Research Database (Denmark)

    Olsson, I. Anna S.; Sandøe, Peter

    2011-01-01

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

  8. Modelling Farm Animal Welfare

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    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

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

  9. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD).

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    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-05-06

    Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg, i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for subsequent methylphenidate-induced conditioned place preference (CPP) and self-administration. Thereafter, the differentially expressed genes in the prefrontal cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which showed CPP to and self-administration of methylphenidate, were analyzed. Genome-wide transcriptome profiling analyses revealed 30 differentially expressed genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9, Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1, Jam2, Asap1). In contrast, 306 genes were differentially expressed in the striatum and among them, 252 were downregulated. The main functional categories overrepresented among the downregulated genes include those involved in cell adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp, Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1, Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic

  10. Modelling Farm Animal Welfare

    Directory of Open Access Journals (Sweden)

    Chérie E. Part

    2013-05-01

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

  11. Animal models of tinnitus.

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    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

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

  12. Animal models of sarcoidosis.

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

    2017-03-01

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

  13. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

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    Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

    2016-01-01

    Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Animal Models of Hemophilia

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

    2013-01-01

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

  15. Animating climate model data

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

    2006-05-01

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

  16. ANIMAL MODELS IN SURGICAL

    African Journals Online (AJOL)

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    experiment also requires a project license. Finally, ... driving, overloading, torture, terrifying or cause or process or permit any animal to be so treated, Cause or permit .... all in an attempt to eliminate or reduce to a minimum discomfort and pain ...

  17. ANIMAL MODELS FOR IMMUNOTOXICITY

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

  18. Animal models of cerebral ischemia

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

    2015-11-01

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

  19. Animal Models in Burn Research

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

    2014-01-01

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

  20. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

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    Yoo, C-H; Lim, S-I [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ({sup 1}H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo {sup 1}H MRS. Methods: We used high-field {sup 1}H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  1. SU-F-I-67: Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

    International Nuclear Information System (INIS)

    Yoo, C-H; Lim, S-I; Song, K-H; Choe, B-Y; Woo, D-C

    2016-01-01

    Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy ("1H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo "1H MRS. Methods: We used high-field "1H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 µL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min. Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively. Conclusion: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo 1H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.

  2. Animal Models for Candidiasis

    Science.gov (United States)

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

    2014-01-01

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

  3. An animal model for tinnitus.

    Science.gov (United States)

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

    1988-03-01

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

  4. High in situ repeatability of behaviour indicates animal personality in the beadlet anemone Actinia equina (Cnidaria.

    Directory of Open Access Journals (Sweden)

    Mark Briffa

    Full Text Available 'Animal personality' means that individuals differ from one another in either single behaviours or suites of related behaviours in a way that is consistent over time. It is usually assumed that such consistent individual differences in behaviour are driven by variation in how individuals respond to information about their environment, rather than by differences in external factors such as variation in microhabitat. Since behavioural variation is ubiquitous in nature we might expect 'animal personality' to be present in diverse taxa, including animals with relatively simple nervous systems. We investigated in situ startle responses in a sea anemone, Actinia equina, to determine whether personalities might be present in this example of an animal with a simple nervous system. We found very high levels of repeatability among individuals that were re-identified in the same locations over a three week sampling period. In a subset of the data, where we used tide-pool temperature measurements to control for a key element of variation in microhabitat, these high levels of repeatability remained. Although a range of other consistent differences in micro-habitat features could have contributed to consistent differences between the behaviour of individuals, these data suggest the presence of animal personality in A. equina. Rather than being restricted to certain groups, personality may be a general feature of animals and may be particularly pronounced in species with simple nervous systems.

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

    Science.gov (United States)

    Sekimizu, N; Paudel, A; Hamamoto, H

    2012-08-01

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

  6. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  7. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. Animal Models of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Carlos Zaragoza

    2011-01-01

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

  9. Animal models of cardiovascular diseases.

    Science.gov (United States)

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

    2011-01-01

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

  10. Animal models of cardiac cachexia.

    Science.gov (United States)

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

    2016-09-15

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

  11. Animal Models for Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Helieh S. Oz

    2011-01-01

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

  12. Animal Models for Periodontal Disease

    Science.gov (United States)

    Oz, Helieh S.; Puleo, David A.

    2011-01-01

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

  13. Animal models for auditory streaming

    Science.gov (United States)

    Itatani, Naoya

    2017-01-01

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

  14. Animal models of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Snehlata V Gajbhiye

    2015-01-01

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

  15. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

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

  16. Animal Models of Zika Virus

    Science.gov (United States)

    Bradley, Michael P; Nagamine, Claude M

    2017-01-01

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

  17. Animal models of drug addiction.

    Science.gov (United States)

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

    2017-09-29

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

  18. Animal model of thermal injuries

    Directory of Open Access Journals (Sweden)

    F. Bečić

    2003-11-01

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

  19. Animal Models of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2014-12-01

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

  20. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    International Nuclear Information System (INIS)

    Bagchi, Manjari

    2017-01-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  1. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    Energy Technology Data Exchange (ETDEWEB)

    Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  2. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads...... to sphericity assumptions, use of F tests and the Greenhouse-Geisser and Huynh-Feldt adjustments to compensate for deviations from sphericity. During a recent implementation of such methods in the R language, the general structure of such transformations was reconsidered, leading to a flexible specification...

  3. Parathyroid diseases and animal models.

    Science.gov (United States)

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

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

  4. Polycystic ovarian disease: animal models.

    Science.gov (United States)

    Mahajan, D K

    1988-12-01

    The reproductive systems of human beings and other vertebrates are grossly similar. In the ovary particularly, the biochemical and physiologic processes are identical not only in the formation of germ cells, the development of primordial follicles and their subsequent growth to Graafian follicles, and eventual ovulation but also in anatomic structure. In a noncarcinogenic human ovary, hypersecretion of androgen causes PCOD. Such hypersecretion may result from a nonpulsatile, constant elevated level of circulating LH or a disturbance in the action of neurotransmitters in the hypothalamus. In studying the pathophysiology of PCOD in humans, one must be aware of the limitations for manipulating the hypothalamic-pituitary axis. Although the rat is a polytocous rodent, the female has a regular ovarian cyclicity of 4 or 5 days, with distinct proestrus, estrus, and diestrus phases. Inasmuch as PCOD can be experimentally produced in the rat, that species is a good model for studying the pathophysiology of human PCOD. These PCOD models and their validity have been described: (1) estradiol-valerate, (2) DHA, (3) constant-light (LL), and (4) neonatally androgenized. Among these, the LL model is noninvasive and seems superior to the others for study of the pathophysiology of PCOD. The production of the polycystic ovarian condition in the rat by the injection of estrogens or androgens in neonate animals, or estradiol or DHA in adult rats, or the administration of antigonadotropins to these animals all cause a sudden appearance of the persistent estrus state by disturbing the metabolic and physiologic processes, whereas exposure of the adult rat to LL causes polycystic ovaries gradually, similar to what is seen in human idiopathic PCOD. After about 50 days of LL, the rat becomes anovulatory and the ovaries contain thickened tunica albuginea and many atretic follicles, and the tertiary follicles are considerably distended and cystic. The granulosa and theca cells appear normal

  5. Complexity of repeated game model in electric power triopoly

    International Nuclear Information System (INIS)

    Ma Junhai; Ji Weizhuo

    2009-01-01

    According to the repeated game model in electric power duopoly, a triopoly outputs game model is presented. On the basis of some hypotheses, the dynamic characters are demonstrated with theoretical analysis and numerical simulations. The results show that the triopoly model is a chaotic system and it is better than the duopoly model in applications.

  6. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

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

  7. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

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

  8. A General Model for Repeated Audit Controls Using Monotone Subsampling

    OpenAIRE

    Raats, V.M.; van der Genugten, B.B.; Moors, J.J.A.

    2002-01-01

    In categorical repeated audit controls, fallible auditors classify sample elements in order to estimate the population fraction of elements in certain categories.To take possible misclassifications into account, subsequent checks are performed with a decreasing number of observations.In this paper a model is presented for a general repeated audit control system, where k subsequent auditors classify elements into r categories.Two different sub-sampling procedures will be discussed, named 'stra...

  9. Repeat Assessed Values Model for Housing Price Index

    Directory of Open Access Journals (Sweden)

    Carini Manuela

    2017-12-01

    Full Text Available This study proposes an innovative methodology, named Repeat Appraised Price Model (RAV, useful for determining the price index numbers for real estate markets and the corresponding index numbers of hedonic prices of main real estate characteristics in the case of a lack of data. The methodological approach proposed in this paper aims to appraise the time series of price index numbers. It integrates the principles of the method of repeat sales with the peculiarities of the Hedonic Price Method, overcoming the problem of an almost total absence of repeat sales for the same property in a given time range; on the other hand, the technique aims to overcome the limitation of the repeat sales technique concerning the inability to take into account the characteristics of individual properties.

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

    OpenAIRE

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

    2016-01-01

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

  11. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

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

  12. Animal models of cerebral arterial gas embolism

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  15. Repeat-aware modeling and correction of short read errors.

    Science.gov (United States)

    Yang, Xiao; Aluru, Srinivas; Dorman, Karin S

    2011-02-15

    High-throughput short read sequencing is revolutionizing genomics and systems biology research by enabling cost-effective deep coverage sequencing of genomes and transcriptomes. Error detection and correction are crucial to many short read sequencing applications including de novo genome sequencing, genome resequencing, and digital gene expression analysis. Short read error detection is typically carried out by counting the observed frequencies of kmers in reads and validating those with frequencies exceeding a threshold. In case of genomes with high repeat content, an erroneous kmer may be frequently observed if it has few nucleotide differences with valid kmers with multiple occurrences in the genome. Error detection and correction were mostly applied to genomes with low repeat content and this remains a challenging problem for genomes with high repeat content. We develop a statistical model and a computational method for error detection and correction in the presence of genomic repeats. We propose a method to infer genomic frequencies of kmers from their observed frequencies by analyzing the misread relationships among observed kmers. We also propose a method to estimate the threshold useful for validating kmers whose estimated genomic frequency exceeds the threshold. We demonstrate that superior error detection is achieved using these methods. Furthermore, we break away from the common assumption of uniformly distributed errors within a read, and provide a framework to model position-dependent error occurrence frequencies common to many short read platforms. Lastly, we achieve better error correction in genomes with high repeat content. The software is implemented in C++ and is freely available under GNU GPL3 license and Boost Software V1.0 license at "http://aluru-sun.ece.iastate.edu/doku.php?id = redeem". We introduce a statistical framework to model sequencing errors in next-generation reads, which led to promising results in detecting and correcting errors

  16. Modeling and evaluating repeatability and reproducibility of ordinal classifications

    NARCIS (Netherlands)

    de Mast, J.; van Wieringen, W.N.

    2010-01-01

    This paper argues that currently available methods for the assessment of the repeatability and reproducibility of ordinal classifications are not satisfactory. The paper aims to study whether we can modify a class of models from Item Response Theory, well established for the study of the reliability

  17. Overview of Animal Models of Obesity

    Science.gov (United States)

    Lutz, Thomas A.; Woods, Stephen C.

    2012-01-01

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

  18. Animal Models of Calcific Aortic Valve Disease

    Directory of Open Access Journals (Sweden)

    Krista L. Sider

    2011-01-01

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

  19. Animal Models of Chemotherapy-induced Mucositis

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  20. Evaluation of animal models of neurobehavioral disorders

    Directory of Open Access Journals (Sweden)

    Nordquist Rebecca E

    2009-02-01

    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

  1. Refinement of a model of repeated cerebrospinal fluid collection in conscious rats.

    Science.gov (United States)

    Amen, Eva Maria; Brecheisen, Muriel; Sach-Peltason, Lisa; Bergadano, Alessandra

    2017-02-01

    The cannulation of the cisterna magna in rats for in vivo sampling of cerebrospinal fluid serves as a valuable model for studying the delivery of new drugs into the central nervous system or disease models. It offers the advantages of repeated sampling without anesthesia-induced bias and using animals as their own controls. An established model was retrospectively reviewed for the outcomes and it was hypothesized that by refining the method, i.e. by (1) implementing pathophysiological-based anesthesia and analgesia, (2) using state-of-the-art peri-operative monitoring and supportive care, (3) increasing stability of the cement-cannula assembly, and (4) selecting a more adaptable animal strain, the outcome in using the model - quantified by peri-operative mortality, survival time and stability of the implant - could be improved and could enhance animal welfare. After refinement of the technique, peri-operative mortality decreased significantly (7 animals out of 73 compared with 4 out of 322; P = 0.001), survival time increased significantly (36 ± 14 days compared with 28 ± 18 days; P concept of Russell and Burch was successfully addressed and animal welfare was improved by (1) the reduction in the total number of animals needed as a result of lower mortality or fewer euthanizations due to technical failure, and frequent use of individual rats over a time frame; and (2) improving the scientific quality of the model.

  2. Animal models: an important tool in mycology.

    Science.gov (United States)

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

    2007-12-01

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

  3. Parâmetros genéticos para a produção de leite de controles individuais de vacas da raça Gir estimados com modelos de repetibilidade e regressão aleatória Estimation of genetic parameters for test day milk records of first lactation Gyr cows using repeatability and random regression animal models

    Directory of Open Access Journals (Sweden)

    Claudio Napolis Costa

    2005-10-01

    número de estimativas negativas entre as PLC do início e fim da lactação do que a FAS. Exceto para a FAS, observou-se redução das estimativas de correlação genética próximas à unidade entre as PLC adjacentes para valores negativos entre as PLC no início e no fim da lactação. Entre os polinômios de Legendre, o de quinta ordem apresentou um melhor o ajuste das PLC. Os resultados indicam o potencial de uso de regressão aleatória, com os modelos LP5 e a FAS apresentando-se como os mais adequados para a modelagem das variâncias genética e de efeito permanente das PLC da raça Gir.Data comprising 8,183 test day records of 1,273 first lactations of Gyr cows from herds supervised by ABCZ were used to estimate variance components and genetic parameters for milk yield using repeatability and random regression animal models by REML. Genetic modelling of logarithmic (FAS, exponential (FW curves was compared to orthogonal Legendre polynomials (LP of order 3 to 5. Residual variance was assumed to be constant in all (ME=1 or some periods of lactation (ME=4. Lactation milk yield in 305-d was also adjusted by an animal model. Genetic variance, heritability and repeatability for test day milk yields estimated by a repeatability animal model were 1.74 kg2, 0.27, and 0.76, respectively. Genetic variance and heritability estimates for lactation milk yield were respectively 121,094.6 and 0.22. Heritability estimates from FAS and FW, respectively, decreased from 0,59 and 0.74 at the beginning of lactation to 0.20 at the end of the period. Except for a fifth-order LP with ME=1, heritability estimates decreased from around 0,70 at early lactation to 0,30 at the end of lactation. Residual variance estimates were slightly smaller for logarithimic than for exponential curves both for homogeneous and heterogeneous variance assumptions. Estimates of residual variance in all stages of lactation decreased as the order of LP increased and depended on the assumption about ME

  4. Animal models in fetal medicine and obstetrics

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  5. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

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

  6. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

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

  7. Animal models for cancer and uses thereof

    NARCIS (Netherlands)

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

    2017-01-01

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

  8. Animal models of osteoporosis - necessity and limitations

    Directory of Open Access Journals (Sweden)

    Turner A. Simon

    2001-06-01

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

  9. The case for repeatable analysis with energy economy optimization models

    International Nuclear Information System (INIS)

    DeCarolis, Joseph F.; Hunter, Kevin; Sreepathi, Sarat

    2012-01-01

    Energy economy optimization (EEO) models employ formal search techniques to explore the future decision space over several decades in order to deliver policy-relevant insights. EEO models are a critical tool for decision-makers who must make near-term decisions with long-term effects in the face of large future uncertainties. While the number of model-based analyses proliferates, insufficient attention is paid to transparency in model development and application. Given the complex, data-intensive nature of EEO models and the general lack of access to source code and data, many of the assumptions underlying model-based analysis are hidden from external observers. This paper discusses the simplifications and subjective judgments involved in the model building process, which cannot be fully articulated in journal papers, reports, or model documentation. In addition, we argue that for all practical purposes, EEO model-based insights cannot be validated through comparison to real world outcomes. As a result, modelers are left without credible metrics to assess a model's ability to deliver reliable insight. We assert that EEO models should be discoverable through interrogation of publicly available source code and data. In addition, third parties should be able to run a specific model instance in order to independently verify published results. Yet a review of twelve EEO models suggests that in most cases, replication of model results is currently impossible. We provide several recommendations to help develop and sustain a software framework for repeatable model analysis.

  10. Small Animal Models for Evaluating Filovirus Countermeasures.

    Science.gov (United States)

    Banadyga, Logan; Wong, Gary; Qiu, Xiangguo

    2018-05-11

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

  11. Final model of multicriterionevaluation of animal welfare

    DEFF Research Database (Denmark)

    Bonde, Marianne; Botreau, R; Bracke, MBM

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

  12. Animal models for rotator cuff repair.

    Science.gov (United States)

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

    2016-11-01

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

  13. Basic mechanisms of MCD in animal models.

    Science.gov (United States)

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

    2009-09-01

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

  14. Retinal Cell Degeneration in Animal Models

    Directory of Open Access Journals (Sweden)

    Masayuki Niwa

    2016-01-01

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

  15. Optogenetics in animal model of alcohol addiction

    Science.gov (United States)

    Nalberczak, Maria; Radwanska, Kasia

    2014-11-01

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

  16. Animal models of preeclampsia; uses and limitations.

    LENUS (Irish Health Repository)

    McCarthy, F P

    2012-01-31

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

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

    Science.gov (United States)

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

    2011-12-01

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

  18. Animal models for Gaucher disease research.

    Science.gov (United States)

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

    2011-11-01

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

  19. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    Tamar Farfel-Becker

    2011-11-01

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

  20. Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

    Science.gov (United States)

    Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

    2011-02-15

    The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Arnoldo eSantos

    2015-10-01

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

  2. Modeling intraindividual variability with repeated measures data methods and applications

    CERN Document Server

    Hershberger, Scott L

    2013-01-01

    This book examines how individuals behave across time and to what degree that behavior changes, fluctuates, or remains stable.It features the most current methods on modeling repeated measures data as reported by a distinguished group of experts in the field. The goal is to make the latest techniques used to assess intraindividual variability accessible to a wide range of researchers. Each chapter is written in a ""user-friendly"" style such that even the ""novice"" data analyst can easily apply the techniques.Each chapter features:a minimum discussion of mathematical detail;an empirical examp

  3. Animal models of asthma: utility and limitations

    Directory of Open Access Journals (Sweden)

    Aun MV

    2017-11-01

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

  4. Osteoarthritis: new insights in animal models.

    Science.gov (United States)

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

    2012-01-01

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

  5. Laboratory animal models for esophageal cancer

    Directory of Open Access Journals (Sweden)

    Dhanya Venugopalan Nair

    2016-11-01

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

  6. Osteoarthritis: New Insights in Animal Models

    OpenAIRE

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

    2012-01-01

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

  7. Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

    International Nuclear Information System (INIS)

    Carpenter, R.L.; Barr, F.P.; Leydig, R.L.; Rajala, R.E.

    1979-01-01

    A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch

  8. On model selections for repeated measurement data in clinical studies.

    Science.gov (United States)

    Zou, Baiming; Jin, Bo; Koch, Gary G; Zhou, Haibo; Borst, Stephen E; Menon, Sandeep; Shuster, Jonathan J

    2015-05-10

    Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Animal models of exercise and obesity.

    Science.gov (United States)

    Kasper, Christine E

    2013-01-01

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

  10. Henipavirus Infections: Lessons from Animal Models

    Directory of Open Access Journals (Sweden)

    Kévin P. Dhondt

    2013-04-01

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

  11. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

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

    2001-01-01

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

  12. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

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

  13. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Animal models to study plaque vulnerability

    NARCIS (Netherlands)

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

    2007-01-01

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

  15. Animal model of human disease. Multiple myeloma

    NARCIS (Netherlands)

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

    1988-01-01

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

  16. Braking System Modeling and Brake Temperature Response to Repeated Cycle

    Directory of Open Access Journals (Sweden)

    Zaini Dalimus

    2014-12-01

    Full Text Available Braking safety is crucial while driving the passenger or commercial vehicles. Large amount of kinetic energy is absorbed by four brakes fitted in the vehicle. If the braking system fails to work, road accident could happen and may result in death. This research aims to model braking system together with vehicle in Matlab/Simulink software and measure actual brake temperature. First, brake characteristic and vehicle dynamic model were generated to estimate friction force and dissipated heat. Next, Arduino based prototype brake temperature monitoring was developed and tested on the road. From the experiment, it was found that brake temperature tends to increase steadily in long repeated deceleration and acceleration cycle.

  17. Animal models of chronic obstructive pulmonary disease.

    Science.gov (United States)

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

    2015-03-01

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

  18. Animal models of obesity and diabetes mellitus

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  19. Large Mammalian Animal Models of Heart Disease

    Directory of Open Access Journals (Sweden)

    Paula Camacho

    2016-10-01

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

  20. Animal Models of Diverticulosis: Review and Recommendations.

    Science.gov (United States)

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

    2018-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Veronesi Paola

    2007-08-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  3. Animal models of contraception: utility and limitations

    Directory of Open Access Journals (Sweden)

    Liechty ER

    2015-04-01

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

  4. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  5. Animal Cancer Models of Skeletal Metastasis

    Directory of Open Access Journals (Sweden)

    Catherine Hibberd

    2013-01-01

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

  6. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

    International Nuclear Information System (INIS)

    Teng, S.; Tebby, C.; Barcellini-Couget, S.; De Sousa, G.; Brochot, C.; Rahmani, R.; Pery, A.R.R.

    2016-01-01

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.

  7. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

    Energy Technology Data Exchange (ETDEWEB)

    Teng, S.; Tebby, C. [Models for Toxicology and Ecotoxicology Unit, INERIS, Parc Technologique Alata, BP 2, 60550 Verneuil-en-Halatte (France); Barcellini-Couget, S. [ODESIA Neosciences, Sophia Antipolis, 400 route des chappes, 06903 Sophia Antipolis (France); De Sousa, G. [INRA, ToxAlim, 400 route des Chappes, BP, 167 06903 Sophia Antipolis, Cedex (France); Brochot, C. [Models for Toxicology and Ecotoxicology Unit, INERIS, Parc Technologique Alata, BP 2, 60550 Verneuil-en-Halatte (France); Rahmani, R. [INRA, ToxAlim, 400 route des Chappes, BP, 167 06903 Sophia Antipolis, Cedex (France); Pery, A.R.R., E-mail: alexandre.pery@agroparistech.fr [AgroParisTech, UMR 1402 INRA-AgroParisTech Ecosys, 78850 Thiverval Grignon (France); INRA, UMR 1402 INRA-AgroParisTech Ecosys, 78850 Thiverval Grignon (France)

    2016-08-15

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.

  8. Constraints on pulsed emission model for repeating FRB 121102

    Science.gov (United States)

    Kisaka, Shota; Enoto, Teruaki; Shibata, Shinpei

    2017-12-01

    Recent localization of the repeating fast radio burst (FRB) 121102 revealed the distance of its host galaxy and luminosities of the bursts. We investigated constraints on the young neutron star (NS) model, that (a) the FRB intrinsic luminosity is supported by the spin-down energy, and (b) the FRB duration is shorter than the NS rotation period. In the case of a circular cone emission geometry, conditions (a) and (b) determine the NS parameters within very small ranges, compared with that from only condition (a) discussed in previous works. Anisotropy of the pulsed emission does not affect the area of the allowed parameter region by virtue of condition (b). The determined parameters are consistent with those independently limited by the properties of the possible persistent radio counterpart and the circumburst environments such as surrounding materials. Since the NS in the allowed parameter region is older than the spin-down timescale, the hypothetical GRP (giant radio pulse)-like model expects a rapid radio flux decay of ≲1 Jy within a few years as the spin-down luminosity decreases. The continuous monitoring will provide constraints on the young NS models. If no flux evolution is seen, we need to consider an alternative model, e.g., the magnetically powered flare.

  9. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

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

  10. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. Eradication of Transboundary Animal Diseases: Can the Rinderpest Success Story be Repeated?

    Science.gov (United States)

    Thomson, G R; Penrith, M-L

    2017-04-01

    A matrix system was developed to aid in the evaluation of the technical amenability to eradication, through mass vaccination, of transboundary animal diseases (TADs). The system involved evaluation of three basic criteria - disease management efficiency, surveillance and epidemiological factors - each in turn comprised of a number of elements (17 in all). On that basis, 25 TADs that have occurred or do occur in southern Africa and for which vaccines are available, in addition to rinderpest (incorporated as a yardstick because it has been eradicated worldwide), were ranked. Cluster analysis was also applied using the same criteria to the 26 diseases, creating division into three groups. One cluster contained only diseases transmitted by arthropods (e.g. African horse sickness and Rift Valley fever) and considered difficult to eradicate because technologies for managing parasitic arthropods on a large scale are unavailable, while a second cluster contained diseases that have been widely considered to be eradicable [rinderpest, canine rabies, the Eurasian serotypes of foot and mouth disease virus (O, A, C & Asia 1) and peste des petits ruminants] as well classical swine fever, Newcastle disease and lumpy skin disease. The third cluster contained all the other TADs evaluated with the implication that these constitute TADs that would be more difficult to eradicate. However, it is acknowledged that the scores assigned in the course of this study may be biased. The point is that the system proposed offers an objective method for assessment of the technical eradicability of TADs; the rankings and groupings derived during this study are less important than the provision of a systematic approach for further development and evaluation. © 2015 Blackwell Verlag GmbH.

  12. Animal model for hepatitis C virus infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2015-01-01

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

  13. Deformation Models Tracking, Animation and Applications

    CERN Document Server

    Torres, Arnau; Gómez, Javier

    2013-01-01

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

  14. Animal models of age related macular degeneration

    Science.gov (United States)

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

    2013-01-01

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

  15. Animal models for Gaucher disease research

    OpenAIRE

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

    2011-01-01

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

  16. Animal Models Utilized in HTLV-1 Research

    Directory of Open Access Journals (Sweden)

    Amanda R. Panfil

    2013-01-01

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

  17. Animal Modeling and Neurocircuitry of Dual Diagnosis

    Science.gov (United States)

    Chambers, R. Andrew

    2010-01-01

    Dual diagnosis is a problem of tremendous depth and scope, spanning many classes of mental disorders and addictive drugs. Animal models of psychiatric disorders studied in addiction paradigms suggest a unitary nature of mental illness and addiction vulnerability both on the neurocircuit and clinical-behavioral levels. These models provide platforms for exploring the interactive roles of biological, environmental and developmental factors on neurocircuits commonly involved in psychiatric and addiction diseases. While suggestive of the artifice of segregated research, training, and clinical cultures between psychiatric and addiction fields, this research may lead to more parsimonious, integrative and preventative treatments for dual diagnosis. PMID:20585464

  18. An animal model to study regenerative endodontics.

    Science.gov (United States)

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

    2011-02-01

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

  19. Animal models for HIV/AIDS research

    Science.gov (United States)

    Hatziioannou, Theodora; Evans, David T.

    2015-01-01

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

  20. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

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

  1. Test–retest repeatability of quantitative cardiac 11C-meta-hydroxyephedrine measurements in rats by small animal positron emission tomography

    International Nuclear Information System (INIS)

    Thackeray, James T.; Renaud, Jennifer M.; Kordos, Myra; Klein, Ran; Kemp, Robert A. de; Beanlands, Rob S.B.; DaSilva, Jean N.

    2013-01-01

    Introduction: The norepinephrine analogue 11 C-meta-hydroxyephedrine (HED) has been used to interrogate sympathetic neuronal reuptake in cardiovascular disease. Application for longitudinal studies in small animal models of disease necessitates an understanding of test–retest variability. This study evaluated the repeatability of multiple quantitative cardiac measurements of HED retention and washout and the pharmacological response to reuptake blockade and enhanced norepinephrine levels. Methods: Small animal PET images were acquired over 60 min following HED administration to healthy male Sprague Dawley rats. Paired test and retest scans were undertaken in individual animals over 7 days. Additional HED scans were conducted following administration of norepinephrine reuptake inhibitor desipramine or continuous infusion of exogenous norepinephrine. HED retention was quantified by retention index, standardized uptake value (SUV), monoexponential and one-compartment washout. Plasma and cardiac norepinephrine were measured by high performance liquid chromatography. Results: Test retest variability was lower for retention index (15% ± 12%) and SUV (19% ± 15%) as compared to monoexponential washout rates (21% ± 13%). Desipramine pretreatment reduced myocardial HED retention index by 69% and SUV by 85%. Chase treatment with desipramine increased monoexponential HED washout by 197% compared to untreated controls. Norepinephrine infusion dose-dependently reduced HED accumulation, reflected by both retention index and SUV, with a corresponding increase in monoexponential washout. Plasma and cardiac norepinephrine levels correlated with HED quantitative measurements. Conclusion: The repeatability of HED retention index, SUV, and monoexponential washout supports its suitability for longitudinal PET studies in rats. Uptake and washout of HED are sensitive to acute increases in norepinephrine concentration

  2. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    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...... 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...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  3. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models.

    Science.gov (United States)

    Teng, S; Tebby, C; Barcellini-Couget, S; De Sousa, G; Brochot, C; Rahmani, R; Pery, A R R

    2016-08-15

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

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

  5. ANIMAL BEHAVIOR AND WELL-BEING SYMPOSIUM: The Common Swine Industry Audit: Future steps to assure positive on-farm animal welfare utilizing validated, repeatable and feasible animal-based measures.

    Science.gov (United States)

    Pairis-Garcia, M; Moeller, S J

    2017-03-01

    The Common Swine Industry Audit (CSIA) was developed and scientifically evaluated through the combined efforts of a task force consisting of university scientists, veterinarians, pork producers, packers, processers, and retail and food service personnel to provide stakeholders throughout the pork chain with a consistent, reliable, and verifiable system to ensure on-farm swine welfare and food safety. The CSIA tool was built from the framework of the Pork Quality Assurance Plus (PQA Plus) site assessment program with the purpose of developing a single, common audit platform for the U.S. swine industry. Twenty-seven key aspects of swine care are captured and evaluated in CSIA and cover the specific focal areas of animal records, animal observations, facilities, and caretakers. Animal-based measures represent approximately 50% of CSIA evaluation criteria and encompass critical failure criteria, including observation of willful acts of abuse and determination of timely euthanasia. Objective, science-based measures of animal well-being parameters (e.g., BCS, lameness, lesions, hernias) are assessed within CSIA using statistically validated sample sizes providing a detection ability of 1% with 95% confidence. The common CSIA platform is used to identify care issues and facilitate continuous improvement in animal care through a validated, repeatable, and feasible animal-based audit process. Task force members provide continual updates to the CSIA tool with a specific focus toward 1) identification and interpretation of appropriate animal-based measures that provide inherent value to pig welfare, 2) establishment of acceptability thresholds for animal-based measures, and 3) interpretation of CSIA data for use and improvement of welfare within the U.S. swine industry.

  6. Animal model of neuropathic tachycardia syndrome

    Science.gov (United States)

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

    2001-01-01

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

  7. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    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.

  8. Towards an animal model of callousness.

    Science.gov (United States)

    Hernandez-Lallement, Julen; van Wingerden, Marijn; Kalenscher, Tobias

    2016-12-28

    Callous-unemotional traits - the insensitivity to other's welfare and well-being - are characterized by a lack of empathy. They are characteristic of psychopathy and can be found in other anti-social disorders, such as conduct disorder. Because of the increasing prevalence of anti-social disorders and the rising societal costs of violence and aggression, it is of great importance to elucidate the psychological and physiological mechanisms underlying callousness in the search for pharmacological treatments. One promising avenue is to create a relevant animal model to explore the neural bases of callousness. Here, we review recent advances in rodent models of pro-social choice that could be applied to probe the absence of pro-sociality as a proxy of callous behavior, and provide future directions for the exploration of the neural substrates of callousness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Animal models for investigating chronic pancreatitis

    Science.gov (United States)

    2011-01-01

    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

  10. A General Model for Repeated Audit Controls Using Monotone Subsampling

    NARCIS (Netherlands)

    Raats, V.M.; van der Genugten, B.B.; Moors, J.J.A.

    2002-01-01

    In categorical repeated audit controls, fallible auditors classify sample elements in order to estimate the population fraction of elements in certain categories.To take possible misclassifications into account, subsequent checks are performed with a decreasing number of observations.In this paper a

  11. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohan Kumar Pasupuleti

    2016-01-01

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

  14. Analysis of a kinetic multi-segment foot model. Part I: Model repeatability and kinematic validity.

    Science.gov (United States)

    Bruening, Dustin A; Cooney, Kevin M; Buczek, Frank L

    2012-04-01

    Kinematic multi-segment foot models are still evolving, but have seen increased use in clinical and research settings. The addition of kinetics may increase knowledge of foot and ankle function as well as influence multi-segment foot model evolution; however, previous kinetic models are too complex for clinical use. In this study we present a three-segment kinetic foot model and thorough evaluation of model performance during normal gait. In this first of two companion papers, model reference frames and joint centers are analyzed for repeatability, joint translations are measured, segment rigidity characterized, and sample joint angles presented. Within-tester and between-tester repeatability were first assessed using 10 healthy pediatric participants, while kinematic parameters were subsequently measured on 17 additional healthy pediatric participants. Repeatability errors were generally low for all sagittal plane measures as well as transverse plane Hindfoot and Forefoot segments (median<3°), while the least repeatable orientations were the Hindfoot coronal plane and Hallux transverse plane. Joint translations were generally less than 2mm in any one direction, while segment rigidity analysis suggested rigid body behavior for the Shank and Hindfoot, with the Forefoot violating the rigid body assumptions in terminal stance/pre-swing. Joint excursions were consistent with previously published studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

    Roy, Sumit; Laerum, Frode; Brosstad, Frank; Kvernebo, Knut; Sakariassen, Kjell S.

    1998-01-01

    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

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

    Science.gov (United States)

    Rodgers, R J

    1997-11-01

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

  17. RASopathies: unraveling mechanisms with animal models

    Directory of Open Access Journals (Sweden)

    Granton A. Jindal

    2015-08-01

    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.

  18. Repeatability of the Oxford Foot Model in children with foot deformity

    NARCIS (Netherlands)

    McCahill, Jennifer; Stebbins, Julie; Koning, Bart; Harlaar, Jaap; Theologis, Tim

    Introduction The Oxford Foot Model (OFM) is a multi-segment, kinematic model developed to assess foot motion. It has previously been assessed for repeatability in healthy populations. To determine the OFM's reliability for detecting foot deformity, it is important to know repeatability in

  19. Effect of Saraswatarishta in animal models of behavior despair

    Directory of Open Access Journals (Sweden)

    Reshma R Parekar

    2014-01-01

    Full Text Available Background: Saraswatarishta (SA is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ′Saraswatarishta′(SA alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part were randomized into 6 groups- Group 1: Distilled water (1 mL, Group 2: Imipramine (30 mg/kg, Group 3: Fluoxetine (10 mg/kg, Group 4: SA (1.8 mL/kg, Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST with single exposure to FST (Part 1 and repeated exposure for 14 days (Part 2. In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4. In each part, rats were subjected to open field test (OFT for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti-depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co-administration with fluoxetine showed more promising effects.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  1. Wound healing in animal models: review article

    Directory of Open Access Journals (Sweden)

    Fariba Jaffary

    2017-10-01

    Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

  2. [Computer optical topography: a study of the repeatability of the results of human body model examination].

    Science.gov (United States)

    Sarnadskiĭ, V N

    2007-01-01

    The problem of repeatability of the results of examination of a plastic human body model is considered. The model was examined in 7 positions using an optical topograph for kyphosis diagnosis. The examination was performed under television camera monitoring. It was shown that variation of the model position in the camera view affected the repeatability of the results of topographic examination, especially if the model-to-camera distance was changed. A study of the repeatability of the results of optical topographic examination can help to increase the reliability of the topographic method, which is widely used for medical screening of children and adolescents.

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

    Science.gov (United States)

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

    2009-01-01

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

  4. Autoshaping of ethanol drinking: an animal model of binge drinking.

    Science.gov (United States)

    Tomie, Arthur; di Poce, Jason; Derenzo, Christopher C; Pohorecky, Larissa A

    2002-01-01

    To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (CS) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedures and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminated from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the presentation of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of ethanol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

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

    International Nuclear Information System (INIS)

    Wu Xilin; Yang Feng

    2002-01-01

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

  6. Experimental animal models for COPD: a methodological review

    Directory of Open Access Journals (Sweden)

    Vahideh Ghorani

    2017-05-01

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

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

    International Nuclear Information System (INIS)

    Wagner, Kay-Uwe

    2004-01-01

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

  8. The genetic analysis of repeated measures I: Simplex models

    NARCIS (Netherlands)

    Molenaar, P.C.M.; Boomsma, D.I.

    1987-01-01

    Extends the simplex model to a model that may be used for the genetic and environmental analysis of covariance (ANCOVA) structures. This "double" simplex structure can be specified as a linear structural relationships model. It is shown that data that give rise to a simplex correlation structure,

  9. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

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

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

    CERN Document Server

    Blain, John M

    2014-01-01

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

  11. The necessity of animal models in pain research.

    Science.gov (United States)

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

    2010-10-01

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

  12. Modeling Behavior and Variation for Crowd Animation

    Science.gov (United States)

    2009-08-01

    characters and environments with- out having to design new behavior graphs. For example, we generated animations for a skateboarder and a horse using...also have motion data for a skateboarder and a horse. Their graphs are similar to the one in Figure 3.3 right. For the skateboarder , there are five

  13. Animation of 3D Model of Human Head

    Directory of Open Access Journals (Sweden)

    V. Michalcin

    2007-04-01

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

  14. Animal Model Selection for Inhalational HCN Exposure

    Science.gov (United States)

    2016-08-01

    effects. Following acute inhalation exposure in humans and animals, cyanide is found in the lung, heart, blood , kidneys, and brain (Ballantyne, 1983...Pritchard, 2007). Other direct or secondary effects associated with CN are reacting with the ferric and carbonyl group of enzymes (e.g. catalase...mechanisms occurs before myocardial depression. Clinically, an initial period of bradycardia and hypertension may occur, followed by hypotension with reflex

  15. Animal Models of Compulsive Eating Behavior

    OpenAIRE

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

    2014-01-01

    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-medica...

  16. Modeling of oxide reduction in repeated-batch pyroprocessing

    International Nuclear Information System (INIS)

    Lee, Hyo Jik; Im, Hun Suk; Park, Geun Il

    2016-01-01

    Highlights: • Pyroprocessing is a complicated batch-type operation. • Discrete event system modeling was used to create an integrated operation model. • Simulation showed that could be accomplished. • The dynamic material flow helps us understand the process operation. • We showed that complex material flow could be simulated in terms of mass balance. - Abstract: Pyroprocessing is a complicated batch-type operation, involving a highly complex material flow logic with a huge number of unit processes. Discrete event system modeling was used to create an integrated operation model for which simulation showed that dynamic material flow could be accomplished to provide considerable insight into the process operation. In the model simulation, the amount of material transported upstream and downstream in the process satisfies a mass balance equation while considering the hold-up incurred by every batch operation. This study also simulated, in detail, an oxide reduction group process embracing electrolytic reduction, cathode processing, and salt purification. Based on the default operation scenario, it showed that complex material flows could be precisely simulated in terms of the mass balance. Specifically, the amount of high-heat elements remaining in the molten salt bath is analyzed to evaluate the operation scenario.

  17. Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment.

    Science.gov (United States)

    Mouri, Akihiro; Noda, Yukihiro; Enomoto, Takeshi; Nabeshima, Toshitaka

    2007-01-01

    In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficits and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of schizophrenia, schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia.

  18. Aspects of animal models for major neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Lefter Radu

    2014-01-01

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

  19. The Use of Animal Models in Behavioural Neuroscience Research

    NARCIS (Netherlands)

    Bovenkerk, B.; Kaldewaij, F.

    2015-01-01

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

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

    NARCIS (Netherlands)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

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

  1. Stress and adaptation : Toward ecologically relevant animal models

    NARCIS (Netherlands)

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

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

  2. Animals

    International Nuclear Information System (INIS)

    Skuterud, L.; Strand, P.; Howard, B.J.

    1997-01-01

    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)

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Science.gov (United States)

    Sliva, Katja

    2015-02-01

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

  5. Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

    Science.gov (United States)

    Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

    2015-08-01

    Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. Published by Elsevier Inc.

  6. Animal Models of Hemophilia and Related Bleeding Disorders

    Science.gov (United States)

    Lozier, Jay N.; Nichols, Timothy C.

    2013-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

  8. Time series sightability modeling of animal populations.

    Science.gov (United States)

    ArchMiller, Althea A; Dorazio, Robert M; St Clair, Katherine; Fieberg, John R

    2018-01-01

    Logistic regression models-or "sightability models"-fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT) estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces) surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only) analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model) with year-specific parameters and a temporally-smoothed model (TS model) that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.

  9. Animator

    Science.gov (United States)

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  10. Using Computational and Mechanical Models to Study Animal Locomotion

    OpenAIRE

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

    2012-01-01

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

  11. Animal models of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Sagvolden Terje

    2005-07-01

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

  12. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

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

    2017-07-01

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

  13. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    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). 68 refs.

  14. Time series sightability modeling of animal populations

    Science.gov (United States)

    ArchMiller, Althea A.; Dorazio, Robert; St. Clair, Katherine; Fieberg, John R.

    2018-01-01

    Logistic regression models—or “sightability models”—fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT) estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces) surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only) analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model) with year-specific parameters and a temporally-smoothed model (TS model) that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.

  15. IVIM: modeling, experimental validation and application to animal models

    International Nuclear Information System (INIS)

    Fournet, Gabrielle

    2016-01-01

    This PhD thesis is centered on the study of the IVIM ('Intravoxel Incoherent Motion') MRI sequence. This sequence allows for the study of the blood microvasculature such as the capillaries, arterioles and venules. To be sensitive only to moving groups of spins, diffusion gradients are added before and after the 180 degrees pulse of a spin echo (SE) sequence. The signal component corresponding to spins diffusing in the tissue can be separated from the one related to spins travelling in the blood vessels which is called the IVIM signal. These two components are weighted by f IVIM which represents the volume fraction of blood inside the tissue. The IVIM signal is usually modelled by a mono-exponential (ME) function and characterized by a pseudo-diffusion coefficient, D*. We propose instead a bi-exponential IVIM model consisting of a slow pool, characterized by F slow and D* slow corresponding to the capillaries as in the ME model, and a fast pool, characterized by F fast and D* fast, related to larger vessels such as medium-size arterioles and venules. This model was validated experimentally and more information was retrieved by comparing the experimental signals to a dictionary of simulated IVIM signals. The influence of the pulse sequence, the repetition time and the diffusion encoding time was also studied. Finally, the IVIM sequence was applied to the study of an animal model of Alzheimer's disease. (author) [fr

  16. Immunobiological outcomes of repeated chlamydial infection from two models of within-host population dynamics.

    Directory of Open Access Journals (Sweden)

    David M Vickers

    Full Text Available BACKGROUND: Chlamydia trachomatis is a common human pathogen that mediates disease processes capable of inflicting serious complications on reproduction. Aggressive inflammatory immune responses are thought to not only direct a person's level of immunity but also the potential for immunopathology. With human immunobiology being debated as a cause of prevailing epidemiological trends, we examined some fundamental issues regarding susceptibility to multiple chlamydial infections that could have implications for infection spread. We argue that, compared to less-frequent exposure, frequent exposure to chlamydia may well produce unique immunobiological characteristics that likely to have important clinical and epidemiological implications. METHODS AND RESULTS: As a novel tool for studying chlamydia, we applied principles of modeling within-host pathogen dynamics to enable an understanding of some fundamental characteristics of an individual's immunobiology during multiple chlamydial infections. While the models were able to reproduce shorter-term infection kinetics of primary and secondary infections previously observed in animal models, it was also observed that longer periods between initial and second infection may increase an individual's chlamydial load and lengthen their duration of infectiousness. The cessation of short-term repeated exposure did not allow for the formation of long-lasting immunity. However, frequent re-exposure non-intuitively linked the formation of protective immunity, persistent infection, and the potential for immunopathology. CONCLUSIONS: Overall, these results provide interesting insights that should be verified with continued study. Nevertheless, these results appear to raise challenges for current evidence of the development of long-lasting immunity against chlamydia, and suggest the existence of a previously unidentified mechanism for the formation of persistent infection. The obvious next goal is to investigate the

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

    OpenAIRE

    Eldridge S. Adams; Michael Mesterton-Gibbons

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

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

  19. Kinematic repeatability of a multi-segment foot model for dance.

    Science.gov (United States)

    Carter, Sarah L; Sato, Nahoko; Hopper, Luke S

    2018-03-01

    The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux. Intra and inter-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability for the first metatarsophalangeal joint in the sagittal plane. Intra-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability during flex-point-flex across all inter-segmental angles except for the tibia-hindfoot and hindfoot-midfoot frontal planes. Inter-assessor repeatability ranged from poor to excellent (0.5 > ICC ≥ 0.75) for the 3D segment rotations. The most repeatable measure was the tibia-foot dorsiflexion/plantar flexion articulation whereas the least repeatable measure was the hindfoot-midfoot adduction/abduction articulation. The variation found in the inter-assessor results is likely due to inconsistencies in marker placement. This 3D dance specific multi-segment foot model provides insight into which kinematic measures can be reliably used to ascertain in vivo technical errors and/or biomechanical abnormalities in a dancer's foot motion.

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

    Science.gov (United States)

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

    2016-03-01

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

  1. Dog as an animal model for neurostimulation.

    Science.gov (United States)

    Hassouna, M; Li, J S; Elhilali, M

    1994-01-01

    The dog provides an important model to study the effect of neural stimulation of different parts of the central and peripheral nervous systems. A multitude of experiments on neurostimulation and neuromodulation to ensure bladder evacuation have been conducted on dogs. The present article reviews the most prominent contributions in the English literature related to neurostimulation using the dog as an experimental model. The various modes of stimulation using dogs as a model and the rationale for their use as well as their shortcomings will be examined. The prominent anatomic features in the neural control of the bladder and the technical aspects involved in neurostimulation of the canine bladder will be reviewed.

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

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

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

  3. Animal models for testing anti-prion drugs.

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

    2017-10-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

  6. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  7. Assessment of Venous Thrombosis in Animal Models.

    Science.gov (United States)

    Grover, Steven P; Evans, Colin E; Patel, Ashish S; Modarai, Bijan; Saha, Prakash; Smith, Alberto

    2016-02-01

    Deep vein thrombosis and common complications, including pulmonary embolism and post-thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here, we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro-computed tomography, and high-frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition. © 2015 American Heart Association, Inc.

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

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

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

  9. Lung cancer risk models from experimental animals

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1988-03-01

    The objective of this paper is to present analyses of data based on methods that adequately account for time-related factors and competiting risks, and that yield results that are expressed in a form comparable to results obtained from recent analyses of epidemiological studies of humans exposed to radon and radon daughters. These epidemiological analyses have modeled the hazard, or age-specific death rates, as a function of factors such as dose and dose rate, time from exposure, and time from cessation of exposure. The starting point for many of the analyses of human data has been the constant relative risk modeling which the age-specific death rates are assumed to be a function of cumulative dose, and the risks due to exposure are assumed to be proportional to the age-specific baseline death rates. However, departures from this initial model, such as dependence of risks on age at risk and/or time from exposure, have been investigated. These analyses have frequently been based on a non-parametric model that requires minimal assumptions regarding the baseline risks and their dependence on age

  10. Modeling animal movements using stochastic differential equations

    Science.gov (United States)

    Haiganoush K. Preisler; Alan A. Ager; Bruce K. Johnson; John G. Kie

    2004-01-01

    We describe the use of bivariate stochastic differential equations (SDE) for modeling movements of 216 radiocollared female Rocky Mountain elk at the Starkey Experimental Forest and Range in northeastern Oregon. Spatially and temporally explicit vector fields were estimated using approximating difference equations and nonparametric regression techniques. Estimated...

  11. Animal and human models to understand ageing.

    Science.gov (United States)

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

    2016-11-01

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

  12. Advances in Animal Models of Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhang Hang

    2015-12-01

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

  13. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

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

  14. Animal models for evaluation of oral delivery of biopharmaceuticals

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Damgaard, Lars Holm

    2007-01-01

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

  16. Parsimonious Structural Equation Models for Repeated Measures Data, with Application to the Study of Consumer Preferences

    Science.gov (United States)

    Elrod, Terry; Haubl, Gerald; Tipps, Steven W.

    2012-01-01

    Recent research reflects a growing awareness of the value of using structural equation models to analyze repeated measures data. However, such data, particularly in the presence of covariates, often lead to models that either fit the data poorly, are exceedingly general and hard to interpret, or are specified in a manner that is highly data…

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

    Directory of Open Access Journals (Sweden)

    Keizo Kanasaki

    2011-01-01

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

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

    Science.gov (United States)

    Tilles, Paulo F C; Petrovskii, Sergei V

    2016-07-01

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

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

    Science.gov (United States)

    Crystal, Jonathon D

    2009-03-01

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

  20. Reflected stochastic differential equation models for constrained animal movement

    Science.gov (United States)

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

    2017-01-01

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

  1. Stop staring facial modeling and animation done right

    CERN Document Server

    Osipa, Jason

    2010-01-01

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

  2. Chimeric animal models in human stem cell biology.

    Science.gov (United States)

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

    2009-01-01

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

  3. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

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

  4. Large animal models for vaccine development and testing.

    Science.gov (United States)

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

    2015-01-01

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

  5. Animal Models Used to Explore Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  6. Repeatability of the Oxford Foot Model in children with foot deformity.

    Science.gov (United States)

    McCahill, Jennifer; Stebbins, Julie; Koning, Bart; Harlaar, Jaap; Theologis, Tim

    2018-03-01

    The Oxford Foot Model (OFM) is a multi-segment, kinematic model developed to assess foot motion. It has previously been assessed for repeatability in healthy populations. To determine the OFM's reliability for detecting foot deformity, it is important to know repeatability in pathological conditions. The aim of the study was to assess the repeatability of the OFM in children with foot deformity. Intra-tester repeatability was assessed for 45 children (15 typically developing, 15 hemiplegic, 15 clubfoot). Inter-tester repeatability was assessed in the clubfoot population. The mean absolute differences between testers (clubfoot) and sessions (clubfoot and hemiplegic) were calculated for each of 15 clinically relevant, kinematic variables and compared to typically developing children. Children with clubfoot showed a mean difference between visits of 2.9° and a mean difference between raters of 3.6° Mean absolute differences were within one degree for the intra and inter-rater reliability in 12/15 variables. Hindfoot rotation, forefoot/tibia abduction and forefoot supination were the most variable between testers. Overall the clubfoot data were less variable than the typically developing population. Children with hemiplegia demonstrated slightly higher differences between sessions (mean 4.1°), with the most reliable data in the sagittal plane, and largest differences in the transverse plane. The OFM was designed to measure different types of foot deformity. The results of this study show that it provides repeatable results in children with foot deformity. To be distinguished from measurement artifact, changes in foot kinematics as a result of intervention or natural progression over time must be greater than the repeatability reported here. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Elementary of animal model for percutaneous and ocular penetration

    Directory of Open Access Journals (Sweden)

    Kalpesh Chhotalal Ashara

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Javier Blesa

    2012-01-01

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

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

    Science.gov (United States)

    Earl, Julia E; Zollner, Patrick A

    2017-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Repeated maternal intramuscular or intraamniotic erythromycin incompletely resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy.

    Science.gov (United States)

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Watts, Rory; Megharaj, Smruthi; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Spiller, O Brad; Keelan, Jeffrey A; Newnham, John P

    2014-08-01

    Ureaplasma spp are the most commonly isolated microorganisms in association with preterm birth. Maternal erythromycin administration is a standard treatment for preterm prelabor rupture of membranes. There is little evidence of its effectiveness in eradicating Ureaplasma spp from the intrauterine cavity and fetus. We used a sheep model of intrauterine Ureaplasma spp infection to investigate the efficacy of repeated maternal intramuscular and intraamniotic erythromycin treatment to eradicate such an infection. Thirty ewes with singleton pregnancies received an intraamniotic injection of 10(7) color change units of erythromycin-sensitive Ureaplasma parvum serovar 3 at 55 days' gestation. At 116 days' gestation, 28 ewes with viable fetuses were randomized to receive (1) intraamniotic and maternal intramuscular saline solution treatment (n = 8), (2) single intraamniotic and repeated maternal intramuscular erythromycin treatment (n = 10), or (3) single maternal intramuscular and repeated intraamniotic erythromycin treatment (n = 10). Fetuses were surgically delivered at 125 days' gestation. Treatment efficacy was assessed by culture, quantitative polymerase chain reaction, and histopathologic evaluation. Animals treated with intraamniotic erythromycin had significantly less viable U parvum serovar 3 in the amniotic fluid at delivery. However, neither combination of maternal intramuscular and intraamniotic erythromycin treatment successfully cleared U parvum serovar 3 from the amniotic fluid or fetal tissues. Three de novo erythromycin-resistant U parvum isolates were identified in erythromycin-treated animals. Erythromycin treatment, given both to the ewe and into the amniotic cavity, fails to eradicate intrauterine and fetal U parvum serovar 3 infection and may lead to development of erythromycin resistant U parvum. Copyright © 2014 Mosby, Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

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

  13. Life sciences research in space: The requirement for animal models

    Science.gov (United States)

    Fuller, C. A.; Philips, R. W.; Ballard, R. W.

    1987-01-01

    Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.

  14. Repeatability of the Oxford Foot Model for Kinematic Gait Analysis of the Foot and Ankle

    NARCIS (Netherlands)

    van Hoeve, S.; Vos, J.; Weijers, P.; Verbruggen, J.; Willems, P.; Poeze, M.; Meijer, K.

    2015-01-01

    INTRODUCTION: Kinematic gait analysis via the multi-segmental Oxford foot model (OFM) may be a valuable addition to the biomechanical examination of the foot and ankle. The aim of this study is to assess the repeatability of the OFM in healthy subjects. METHODS: Nine healthy subjects, without a

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

    Directory of Open Access Journals (Sweden)

    HUANG Haiyan

    2014-09-01

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

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

    Science.gov (United States)

    Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

    2011-10-01

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

  17. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

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

  18. Th17 in Animal Models of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Motomu Hashimoto

    2017-07-01

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

  19. Animal Models for Tuberculosis in Translational and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Lingjun Zhan

    2017-05-01

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

  20. Behavioral models of tinnitus and hyperacusis in animals

    Directory of Open Access Journals (Sweden)

    Sarah H Hayes

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    SONAL eGOSWAMI

    2013-05-01

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

  2. Animal models of GM2 gangliosidosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Lawson CA

    2016-07-01

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

  3. Animal models of GM2 gangliosidosis: utility and limitations

    Science.gov (United States)

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

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

  4. Animal Models for the Study of Female Sexual Dysfunction

    Science.gov (United States)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2017-11-01

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

  8. Investigation of dimensional variation in parts manufactured by fused deposition modeling using Gauge Repeatability and Reproducibility

    Science.gov (United States)

    Mohamed, Omar Ahmed; Hasan Masood, Syed; Lal Bhowmik, Jahar

    2018-02-01

    In the additive manufacturing (AM) market, the question is raised by industry and AM users on how reproducible and repeatable the fused deposition modeling (FDM) process is in providing good dimensional accuracy. This paper aims to investigate and evaluate the repeatability and reproducibility of the FDM process through a systematic approach to answer this frequently asked question. A case study based on the statistical gage repeatability and reproducibility (gage R&R) technique is proposed to investigate the dimensional variations in the printed parts of the FDM process. After running the simulation and analysis of the data, the FDM process capability is evaluated, which would help the industry for better understanding the performance of FDM technology.

  9. Mouse Models of C9orf72 Hexanucleotide Repeat Expansion in Amyotrophic Lateral Sclerosis/ Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Ranjan Batra

    2017-07-01

    Full Text Available The presence of hexanucleotide repeat expansion (HRE in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2 HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN translation mechanism, and on loss-of-function of the C9orf72 protein. Immense effort to elucidate these mechanisms has been put forth and toxic gain-of-function models have especially gained attention. Various mouse models that recapitulate distinct disease-related pathological, functional, and behavioral phenotypes have been generated and characterized. Although these models express the C9orf72 HRE mutation, there are numerous differences among them, including the transgenesis approach to introduce G4C2-repeat DNA, genomic coverage of C9orf72 features in the transgene, G4C2-repeat length after genomic stabilization, spatiotemporal expression profiles of RNA foci and RAN protein aggregates, neuropathological features, and neurodegeneration-related clinical symptoms. This review aims to (1 provide an overview of the key characteristics; (2 provide insights into potential pathological factors contributing to neurotoxicity and clinical phenotypes through systematic comparison of these models.

  10. Joint modelling of repeated measurement and time-to-event data: an introductory tutorial.

    Science.gov (United States)

    Asar, Özgür; Ritchie, James; Kalra, Philip A; Diggle, Peter J

    2015-02-01

    The term 'joint modelling' is used in the statistical literature to refer to methods for simultaneously analysing longitudinal measurement outcomes, also called repeated measurement data, and time-to-event outcomes, also called survival data. A typical example from nephrology is a study in which the data from each participant consist of repeated estimated glomerular filtration rate (eGFR) measurements and time to initiation of renal replacement therapy (RRT). Joint models typically combine linear mixed effects models for repeated measurements and Cox models for censored survival outcomes. Our aim in this paper is to present an introductory tutorial on joint modelling methods, with a case study in nephrology. We describe the development of the joint modelling framework and compare the results with those obtained by the more widely used approaches of conducting separate analyses of the repeated measurements and survival times based on a linear mixed effects model and a Cox model, respectively. Our case study concerns a data set from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS). We also provide details of our open-source software implementation to allow others to replicate and/or modify our analysis. The results for the conventional linear mixed effects model and the longitudinal component of the joint models were found to be similar. However, there were considerable differences between the results for the Cox model with time-varying covariate and the time-to-event component of the joint model. For example, the relationship between kidney function as measured by eGFR and the hazard for initiation of RRT was significantly underestimated by the Cox model that treats eGFR as a time-varying covariate, because the Cox model does not take measurement error in eGFR into account. Joint models should be preferred for simultaneous analyses of repeated measurement and survival data, especially when the former is measured with error and the association

  11. Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET

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    Adrian F. Ocneanu

    2017-01-01

    Full Text Available Purpose. Myocardial blood flow (MBF quantification with Rb82 positron emission tomography (PET is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic Rb82 PET, from which MBF was quantified using 1-tissue-compartment kinetic model variants: (1 blood-pool versus uptake region sampled input function (Blood/Uptake-ROI, (2 dual spillover correction (SOC-On/Off, (3 right blood correction (RBC-On/Off, (4 arterial blood transit delay (Delay-On/Off, and (5 distribution volume (DV constraint (Global/Regional-DV. Repeatability of MBF, stress/rest myocardial flow reserve (MFR, and stress/rest MBF difference (ΔMBF was assessed using nonparametric reproducibility coefficients (RPCnp = 1.45 × interquartile range. Results. MBF using SOC-On, RVBC-Off, Blood-ROI, Global-DV, and Delay-Off was most repeatable for combined rest and stress: RPCnp = 0.21 mL/min/g (15.8%. Corresponding MFR and ΔMBF RPCnp were 0.42 (20.2% and 0.24 mL/min/g (23.5%. MBF repeatability improved with SOC-On at stress (p<0.001 and tended to improve with RBC-Off at both rest and stress (p<0.08. DV and ROI did not significantly influence repeatability. The Delay-On model was overdetermined and did not reliably converge. Conclusion. MBF and MFR test-retest repeatability were the best with dual spillover correction, left atrium blood input function, and global DV.

  12. Ubiquitous expression of CUG or CAG trinucleotide repeat RNA causes common morphological defects in a Drosophila model of RNA-mediated pathology.

    Directory of Open Access Journals (Sweden)

    Kynan T Lawlor

    Full Text Available Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington's disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 and 2. A shared genetic basis, and overlapping clinical features for some of these diseases, indicate that common pathways may contribute to pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins and expanded repeat RNA, have been identified by the use of model systems, that may account for shared pathology. The use of such animal models enables identification of distinct pathways and their 'molecular hallmarks' that can be used to determine the contribution of each pathway in human pathology. Here we characterise a tergite disruption phenotype in adult flies, caused by ubiquitous expression of either untranslated CUG or CAG expanded repeat RNA. Using the tergite phenotype as a quantitative trait we define a new genetic system in which to examine 'hairpin' repeat RNA-mediated cellular perturbation. Further experiments use this system to examine whether pathways involving Muscleblind sequestration or Dicer processing, which have been shown to mediate repeat RNA-mediated pathology in other model systems, contribute to cellular perturbation in this model.

  13. Animal Models of Tick-Borne Hemorrhagic Fever Viruses

    Directory of Open Access Journals (Sweden)

    Heinz Feldmann

    2013-05-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  15. Perinatal Hypoxia and Ischemia in Animal Models of Schizophrenia

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    Dimitri Hefter

    2018-03-01

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

  16. Animal Models of Diabetic Retinopathy: Summary and Comparison

    Science.gov (United States)

    Lo, Amy C. Y.

    2013-01-01

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

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

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

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

  18. Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.

    Science.gov (United States)

    Ma, Yanyuan; Wang, Yuanjia

    2014-04-15

    Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members. Copyright © 2013 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2012-05-09

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

  20. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Toyoda, Atsushi

    2017-07-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2008-10-01

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

  4. An animal model for the neuromodulation of neurogenic bladder dysfunction.

    Science.gov (United States)

    Zvara, P; Sahi, S; Hassouna, M M

    1998-08-01

    To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

  5. Genetic Evaluation and Ranking of Different Animal Models Using ...

    African Journals Online (AJOL)

    An animal model utilizes all relationships available in a given data set. Estimates for variance components for additive direct, additive maternal, maternal environmental and direct environmental effects, and their covariances between direct and maternal genetic effects for post weaning growth traits have been obtained with ...

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

    African Journals Online (AJOL)

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

  7. Infectious diseases among animals : combining models with data

    NARCIS (Netherlands)

    Koeijer, A.A. de

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the

  8. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. Social Stress in Rats : An Animal Model of Depression?

    NARCIS (Netherlands)

    Koolhaas, J.M.; Meerlo, P.; De Boer, S..; Strubbe, J.H.; Bohus, B.

    1995-01-01

    Our current understanding of the physiological mechanisms underlying depressive disorders is not only based on behavioral, neuroendocrine and pharmacological studies in depressed humans, but also on experimental studies in a wide variety of animal models of depression. Ideally, the two approaches

  10. Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

    NARCIS (Netherlands)

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

    1993-01-01

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

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  12. The miniature pig as an animal model in biomedical research

    Czech Academy of Sciences Publication Activity Database

    Vodička, Petr; Smetana Jr., K.; Dvořánková, B.; Emerick, T.; Xu, Y.; Ourednik, J.; Ourednik, V.; Motlík, Jan

    2005-01-01

    Roč. 1049, - (2005), s. 161-171 ISSN 0077-8923 R&D Projects: GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50450515 Keywords : animal model * stem cell * transgenic pig Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.971, year: 2005

  13. Animal Models of Diabetes Mellitus for Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Naoaki Sakata

    2012-01-01

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

  14. An Experimental Animal Model for Abdominal Fascia Healing after Surgery

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H-C; Klein, M

    2013-01-01

    be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia......Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

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

    Science.gov (United States)

    Chujitarom, Wannaporn; Piriyasurawong, Pallop

    2017-01-01

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

  16. Computer-animated model of accommodation and presbyopia.

    Science.gov (United States)

    Goldberg, Daniel B

    2015-02-01

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

  17. Experimental protocols for behavioral imaging: seeing animal models of drug abuse in a new light.

    Science.gov (United States)

    Aarons, Alexandra R; Talan, Amanda; Schiffer, Wynne K

    2012-01-01

    Behavioral neuroimaging is a rapidly evolving discipline that represents a marriage between the fields of behavioral neuroscience and preclinical molecular imaging. This union highlights the changing role of imaging in translational research. Techniques developed for humans are now widely applied in the study of animal models of brain disorders such as drug addiction. Small animal or preclinical imaging allows us to interrogate core features of addiction from both behavioral and biological endpoints. Snapshots of brain activity allow us to better understand changes in brain function and behavior associated with initial drug exposure, the emergence of drug escalation, and repeated bouts of drug withdrawal and relapse. Here we review the development and validation of new behavioral imaging paradigms and several clinically relevant radiotracers used to capture dynamic molecular events in behaving animals. We will discuss ways in which behavioral imaging protocols can be optimized to increase throughput and quantitative methods. Finally, we discuss our experience with the practical aspects of behavioral neuroimaging, so investigators can utilize effective animal models to better understand the addicted brain and behavior.

  18. Discussion on the establishment of blood glucose fluctuation animal models

    OpenAIRE

    Chun-Liu Gai; Jing-Ru Zhao; Xiao-Long Chen

    2014-01-01

    AIM: To provide the experimental basis for the in vivo study of blood glucose fluctuation injury mechanism, through intraperitoneal injection of glucose to establish blood glucose fluctuation animal models and to simulate blood glucose fluctuation of patients with diabetes.METHODS: Rats were randomly divided into four groups: normal control group(NC), normal fluctuation group(NF), diabetes mellitus group(DM)and diabetes fluctuation group(DF). Diabetic models were induced through intraperitone...

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-05-14

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

  1. Tupaia belangeri as an experimental animal model for viral infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  2. Animal models for Ebola and Marburg virus infections

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

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

  3. Animal models for Ebola and Marburg virus infections

    Directory of Open Access Journals (Sweden)

    Eri eNakayama

    2013-09-01

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

  4. Extent of Mycobacterium bovis transmission among animals of dairy and beef cattle and deer farms in South Korea determined by variable-number tandem repeats typing.

    Science.gov (United States)

    Je, Sungmo; Ku, Bok Kyung; Jeon, Bo-Young; Kim, Jae-Myoung; Jung, Suk-Chan; Cho, Sang-Nae

    2015-04-17

    Identifying sources of Mycobacterium bovis transmission would be essential for establishing effective control programs of bovine tuberculosis (TB), a major zoonosis threatening human health worldwide. As an effort to determine the extent of M. bovis transmission among dairy and beef cattle and deer populations, a mycobacterial interspersed repetitive units (MIRU)-variable-number tandem repeats (VNTR) typing method was employed for analysis of 131 M. bovis isolates from 59 Holstein dairy cattle, 39 Korean beef cattle, and 33 deer. Of 31 MIRU-VNTR markers, 15 showed allelic diversity. The most discriminatory locus for M. bovis isolates was VNTR 3336 (h=0.59) followed by QUB 26, MIRU 31, VNTR 2401, and VNTR 3171 which showed high discriminatory power (h=0.43). The combined VNTR loci had an allelic diversity of 0.83. On the basis of the VNTR profiles of 30 VNTR loci, 24 genotypes were identified, and two genotypes were highly prevalent among all M. bovis isolates (33.6% and 19.1%, respectively), thus indicating that more than 50% of the isolates shared common molecular characteristics. Six additional genotypes were common in 2 of the 3 animal species, suggesting a wide interspecies transmission of M. bovis. This study thus demonstrates that MIRU-VNTR typing is useful in differentiation of M. bovis isolates and that M. bovis transmission occurs frequently among farmed animal species, highlighting the importance of bovine TB control programs in different animal species which are often raised in the same villages. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Animal models of enterovirus 71 infection: applications and limitations

    Science.gov (United States)

    2014-01-01

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252

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

    Directory of Open Access Journals (Sweden)

    Enderli TA

    2016-09-01

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

  7. A method of shadow puppet figure modeling and animation

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Science.gov (United States)

    Roth, J A; Flaming, K P

    1990-01-01

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

  9. Multi-scale inference of interaction rules in animal groups using Bayesian model selection.

    Directory of Open Access Journals (Sweden)

    Richard P Mann

    Full Text Available Inference of interaction rules of animals moving in groups usually relies on an analysis of large scale system behaviour. Models are tuned through repeated simulation until they match the observed behaviour. More recent work has used the fine scale motions of animals to validate and fit the rules of interaction of animals in groups. Here, we use a Bayesian methodology to compare a variety of models to the collective motion of glass prawns (Paratya australiensis. We show that these exhibit a stereotypical 'phase transition', whereby an increase in density leads to the onset of collective motion in one direction. We fit models to this data, which range from: a mean-field model where all prawns interact globally; to a spatial Markovian model where prawns are self-propelled particles influenced only by the current positions and directions of their neighbours; up to non-Markovian models where prawns have 'memory' of previous interactions, integrating their experiences over time when deciding to change behaviour. We show that the mean-field model fits the large scale behaviour of the system, but does not capture the observed locality of interactions. Traditional self-propelled particle models fail to capture the fine scale dynamics of the system. The most sophisticated model, the non-Markovian model, provides a good match to the data at both the fine scale and in terms of reproducing global dynamics, while maintaining a biologically plausible perceptual range. We conclude that prawns' movements are influenced by not just the current direction of nearby conspecifics, but also those encountered in the recent past. Given the simplicity of prawns as a study system our research suggests that self-propelled particle models of collective motion should, if they are to be realistic at multiple biological scales, include memory of previous interactions and other non-Markovian effects.

  10. Multi-scale inference of interaction rules in animal groups using Bayesian model selection.

    Directory of Open Access Journals (Sweden)

    Richard P Mann

    2012-01-01

    Full Text Available Inference of interaction rules of animals moving in groups usually relies on an analysis of large scale system behaviour. Models are tuned through repeated simulation until they match the observed behaviour. More recent work has used the fine scale motions of animals to validate and fit the rules of interaction of animals in groups. Here, we use a Bayesian methodology to compare a variety of models to the collective motion of glass prawns (Paratya australiensis. We show that these exhibit a stereotypical 'phase transition', whereby an increase in density leads to the onset of collective motion in one direction. We fit models to this data, which range from: a mean-field model where all prawns interact globally; to a spatial Markovian model where prawns are self-propelled particles influenced only by the current positions and directions of their neighbours; up to non-Markovian models where prawns have 'memory' of previous interactions, integrating their experiences over time when deciding to change behaviour. We show that the mean-field model fits the large scale behaviour of the system, but does not capture fine scale rules of interaction, which are primarily mediated by physical contact. Conversely, the Markovian self-propelled particle model captures the fine scale rules of interaction but fails to reproduce global dynamics. The most sophisticated model, the non-Markovian model, provides a good match to the data at both the fine scale and in terms of reproducing global dynamics. We conclude that prawns' movements are influenced by not just the current direction of nearby conspecifics, but also those encountered in the recent past. Given the simplicity of prawns as a study system our research suggests that self-propelled particle models of collective motion should, if they are to be realistic at multiple biological scales, include memory of previous interactions and other non-Markovian effects.

  11. Sleep and Obesity: A focus on animal models

    Science.gov (United States)

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

    2012-01-01

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

  12. Repeatability of a 3D multi-segment foot model protocol in presence of foot deformities.

    Science.gov (United States)

    Deschamps, Kevin; Staes, Filip; Bruyninckx, Herman; Busschots, Ellen; Matricali, Giovanni A; Spaepen, Pieter; Meyer, Christophe; Desloovere, Kaat

    2012-07-01

    Repeatability studies on 3D multi-segment foot models (3DMFMs) have mainly considered healthy participants which contrasts with the widespread application of these models to evaluate foot pathologies. The current study aimed at establishing the repeatability of the 3DMFM described by Leardini et al. in presence of foot deformities. Foot kinematics of eight adult participants were analyzed using a repeated-measures design including two therapists with different levels of experience. The inter-trial variability was higher compared to the kinematics of healthy subjects. Consideration of relative angles resulted in the lowest inter-session variability. The absolute 3D rotations between the Sha-Cal and Cal-Met seem to have the lowest variability in both therapists. A general trend towards higher σ(sess)/σ(trial) ratios was observed when the midfoot was involved. The current study indicates that not only relative 3D rotations and planar angles can be measured consistently in patients, also a number of absolute parameters can be consistently measured serving as basis for the decision making process. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Fixed recurrence and slip models better predict earthquake behavior than the time- and slip-predictable models 1: repeating earthquakes

    Science.gov (United States)

    Rubinstein, Justin L.; Ellsworth, William L.; Chen, Kate Huihsuan; Uchida, Naoki

    2012-01-01

    The behavior of individual events in repeating earthquake sequences in California, Taiwan and Japan is better predicted by a model with fixed inter-event time or fixed slip than it is by the time- and slip-predictable models for earthquake occurrence. Given that repeating earthquakes are highly regular in both inter-event time and seismic moment, the time- and slip-predictable models seem ideally suited to explain their behavior. Taken together with evidence from the companion manuscript that shows similar results for laboratory experiments we conclude that the short-term predictions of the time- and slip-predictable models should be rejected in favor of earthquake models that assume either fixed slip or fixed recurrence interval. This implies that the elastic rebound model underlying the time- and slip-predictable models offers no additional value in describing earthquake behavior in an event-to-event sense, but its value in a long-term sense cannot be determined. These models likely fail because they rely on assumptions that oversimplify the earthquake cycle. We note that the time and slip of these events is predicted quite well by fixed slip and fixed recurrence models, so in some sense they are time- and slip-predictable. While fixed recurrence and slip models better predict repeating earthquake behavior than the time- and slip-predictable models, we observe a correlation between slip and the preceding recurrence time for many repeating earthquake sequences in Parkfield, California. This correlation is not found in other regions, and the sequences with the correlative slip-predictable behavior are not distinguishable from nearby earthquake sequences that do not exhibit this behavior.

  14. Analysis of oligonucleotide array experiments with repeated measures using mixed models

    Directory of Open Access Journals (Sweden)

    Getchell Thomas V

    2004-12-01

    Full Text Available Abstract Background Two or more factor mixed factorial experiments are becoming increasingly common in microarray data analysis. In this case study, the two factors are presence (Patients with Alzheimer's disease or absence (Control of the disease, and brain regions including olfactory bulb (OB or cerebellum (CER. In the design considered in this manuscript, OB and CER are repeated measurements from the same subject and, hence, are correlated. It is critical to identify sources of variability in the analysis of oligonucleotide array experiments with repeated measures and correlations among data points have to be considered. In addition, multiple testing problems are more complicated in experiments with multi-level treatments or treatment combinations. Results In this study we adopted a linear mixed model to analyze oligonucleotide array experiments with repeated measures. We first construct a generalized F test to select differentially expressed genes. The Benjamini and Hochberg (BH procedure of controlling false discovery rate (FDR at 5% was applied to the P values of the generalized F test. For those genes with significant generalized F test, we then categorize them based on whether the interaction terms were significant or not at the α-level (αnew = 0.0033 determined by the FDR procedure. Since simple effects may be examined for the genes with significant interaction effect, we adopt the protected Fisher's least significant difference test (LSD procedure at the level of αnew to control the family-wise error rate (FWER for each gene examined. Conclusions A linear mixed model is appropriate for analysis of oligonucleotide array experiments with repeated measures. We constructed a generalized F test to select differentially expressed genes, and then applied a specific sequence of tests to identify factorial effects. This sequence of tests applied was designed to control for gene based FWER.

  15. Microscopic transport model animation visualisation on KML base

    Science.gov (United States)

    Yatskiv, I.; Savrasovs, M.

    2012-10-01

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

  16. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

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

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

    Science.gov (United States)

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

    2001-09-01

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

  18. An animal model to train Lichtenstein inguinal hernia repair

    DEFF Research Database (Denmark)

    Rosenberg, J; Presch, I; Pommergaard, H C

    2013-01-01

    , thus complicating the procedure if operation should be done in the inguinal canal. The chain of lymph nodes resembles the human spermatic cord and can be used to perform Lichtenstein's hernia repair. RESULTS: This experimental surgical model has been tested on two adult male pigs and three adult female...... pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation...

  19. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    Science.gov (United States)

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.

  20. Cardiovascular Changes in Animal Models of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexandre M. Lehnen

    2013-01-01

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

  1. Gender Differences in Animal Models of Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Hagit Cohen

    2011-01-01

    Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.

  2. Animal models of social anxiety disorder and their validity criteria.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João

    2014-09-26

    Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Animal models for oral transmission of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Sarah E F D'Orazio

    2014-02-01

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

  4. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

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

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

    Science.gov (United States)

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

    2014-12-30

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

  6. Animal models of tic disorders: A translational perspective

    Science.gov (United States)

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

    2014-01-01

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

  7. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    OpenAIRE

    Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

    2015-01-01

    We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

  8. A novel animal model of dysphagia following stroke.

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

    Handforth, Adrian

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lavoie

    2012-01-01

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

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

    Science.gov (United States)

    Hager, Christine

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

  12. The establishment of animal model of acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

    2008-01-01

    Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

  13. Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification.

    Directory of Open Access Journals (Sweden)

    Bonita J Brewer

    2015-12-01

    Full Text Available DNA replication errors are a major driver of evolution--from single nucleotide polymorphisms to large-scale copy number variations (CNVs. Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model--Origin-Dependent Inverted-Repeat Amplification (ODIRA-proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error-the ligation of leading and lagging nascent strands to create "closed" forks-can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent--a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins

  14. Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification.

    Science.gov (United States)

    Brewer, Bonita J; Payen, Celia; Di Rienzi, Sara C; Higgins, Megan M; Ong, Giang; Dunham, Maitreya J; Raghuraman, M K

    2015-12-01

    DNA replication errors are a major driver of evolution--from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model--Origin-Dependent Inverted-Repeat Amplification (ODIRA)-proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error-the ligation of leading and lagging nascent strands to create "closed" forks-can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent--a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of interstitial

  15. Validation of Diagnostic Imaging Based on Repeat Examinations. An Image Interpretation Model

    International Nuclear Information System (INIS)

    Isberg, B.; Jorulf, H.; Thorstensen, Oe.

    2004-01-01

    Purpose: To develop an interpretation model, based on repeatedly acquired images, aimed at improving assessments of technical efficacy and diagnostic accuracy in the detection of small lesions. Material and Methods: A theoretical model is proposed. The studied population consists of subjects that develop focal lesions which increase in size in organs of interest during the study period. The imaging modality produces images that can be re-interpreted with high precision, e.g. conventional radiography, computed tomography, and magnetic resonance imaging. At least four repeat examinations are carried out. Results: The interpretation is performed in four or five steps: 1. Independent readers interpret the examinations chronologically without access to previous or subsequent films. 2. Lesions found on images at the last examination are included in the analysis, with interpretation in consensus. 3. By concurrent back-reading in consensus, the lesions are identified on previous images until they are so small that even in retrospect they are undetectable. The earliest examination at which included lesions appear is recorded, and the lesions are verified by their growth (imaging reference standard). Lesion size and other characteristics may be recorded. 4. Records made at step 1 are corrected to those of steps 2 and 3. False positives are recorded. 5. (Optional) Lesion type is confirmed by another diagnostic test. Conclusion: Applied on subjects with progressive disease, the proposed image interpretation model may improve assessments of technical efficacy and diagnostic accuracy in the detection of small focal lesions. The model may provide an accurate imaging reference standard as well as repeated detection rates and false-positive rates for tested imaging modalities. However, potential review bias necessitates a strict protocol

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

    Science.gov (United States)

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

    2016-04-01

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

  17. Gene therapy in animal models of autosomal dominant retinitis pigmentosa

    Science.gov (United States)

    Rossmiller, Brian; Mao, Haoyu

    2012-01-01

    Gene therapy for dominantly inherited genetic disease is more difficult than gene-based therapy for recessive disorders, which can be treated with gene supplementation. Treatment of dominant disease may require gene supplementation partnered with suppression of the expression of the mutant gene either at the DNA level, by gene repair, or at the RNA level by RNA interference or transcriptional repression. In this review, we examine some of the gene delivery approaches used to treat animal models of autosomal dominant retinitis pigmentosa, focusing on those models associated with mutations in the gene for rhodopsin. We conclude that combinatorial approaches have the greatest promise for success. PMID:23077406

  18. Biochemical correlates in an animal model of depression

    International Nuclear Information System (INIS)

    Johnson, J.O.

    1986-01-01

    A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action

  19. Modelling the interactions between animal venom peptides and membrane proteins.

    Science.gov (United States)

    Hung, Andrew; Kuyucak, Serdar; Schroeder, Christina I; Kaas, Quentin

    2017-12-01

    The active components of animal venoms are mostly peptide toxins, which typically target ion channels and receptors of both the central and peripheral nervous system, interfering with action potential conduction and/or synaptic transmission. The high degree of sequence conservation of their molecular targets makes a range of these toxins active at human receptors. The high selectivity and potency displayed by some of these toxins have prompted their use as pharmacological tools as well as drugs or drug leads. Molecular modelling has played an essential role in increasing our molecular-level understanding of the activity and specificity of animal toxins, as well as engineering them for biotechnological and pharmaceutical applications. This review focuses on the biological insights gained from computational and experimental studies of animal venom toxins interacting with membranes and ion channels. A host of recent X-ray crystallography and electron-microscopy structures of the toxin targets has contributed to a dramatic increase in the accuracy of the molecular models of toxin binding modes greatly advancing this exciting field of study. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Diagnosis of abdominal abscess: A large animal model

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  1. Animal models as tools to study the pathophysiology of depression

    Directory of Open Access Journals (Sweden)

    Helena M. Abelaira

    2013-01-01

    Full Text Available The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

  2. Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

    Directory of Open Access Journals (Sweden)

    GILDA NEVES

    2017-08-01

    Full Text Available ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

  3. Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects.

    Science.gov (United States)

    Neves, Gilda; Borsoi, Milene; Antonio, Camila B; Pranke, Mariana A; Betti, Andresa H; Rates, Stela M K

    2017-01-01

    Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

  4. Development of virtual hands using animation software and graphical modelling

    International Nuclear Information System (INIS)

    Oliveira, Erick da S.; Junior, Alberico B. de C.

    2016-01-01

    The numerical dosimetry uses virtual anthropomorphic simulators to represent the human being in computational framework and thus assess the risks associated with exposure to a radioactive source. With the development of computer animation software, the development of these simulators was facilitated using only knowledge of human anatomy to prepare various types of simulators (man, woman, child and baby) in various positions (sitting, standing, running) or part thereof (head, trunk and limbs). These simulators are constructed by loops of handling and due to the versatility of the method, one can create various geometries irradiation was not possible before. In this work, we have built an exhibition of a radiopharmaceutical scenario manipulating radioactive material using animation software and graphical modeling and anatomical database. (author)

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

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

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

  6. Animal models of gene-environment interactions in schizophrenia.

    Science.gov (United States)

    Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V

    2009-12-07

    The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.

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

    Science.gov (United States)

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

    2014-04-01

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

  8. The virtual craniofacial patient: 3D jaw modeling and animation.

    Science.gov (United States)

    Enciso, Reyes; Memon, Ahmed; Fidaleo, Douglas A; Neumann, Ulrich; Mah, James

    2003-01-01

    In this paper, we present new developments in the area of 3D human jaw modeling and animation. CT (Computed Tomography) scans have traditionally been used to evaluate patients with dental implants, assess tumors, cysts, fractures and surgical procedures. More recently this data has been utilized to generate models. Researchers have reported semi-automatic techniques to segment and model the human jaw from CT images and manually segment the jaw from MRI images. Recently opto-electronic and ultrasonic-based systems (JMA from Zebris) have been developed to record mandibular position and movement. In this research project we introduce: (1) automatic patient-specific three-dimensional jaw modeling from CT data and (2) three-dimensional jaw motion simulation using jaw tracking data from the JMA system (Zebris).

  9. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  10. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan Jana

    2012-01-01

    Full Text Available Angelman syndrome (AS is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.

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

    Science.gov (United States)

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

    2015-06-04

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

  12. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  13. Analyzing Repeated Measures Marginal Models on Sample Surveys with Resampling Methods

    Directory of Open Access Journals (Sweden)

    James D. Knoke

    2005-12-01

    Full Text Available Packaged statistical software for analyzing categorical, repeated measures marginal models on sample survey data with binary covariates does not appear to be available. Consequently, this report describes a customized SAS program which accomplishes such an analysis on survey data with jackknifed replicate weights for which the primary sampling unit information has been suppressed for respondent confidentiality. First, the program employs the Macro Language and the Output Delivery System (ODS to estimate the means and covariances of indicator variables for the response variables, taking the design into account. Then, it uses PROC CATMOD and ODS, ignoring the survey design, to obtain the design matrix and hypothesis test specifications. Finally, it enters these results into another run of CATMOD, which performs automated direct input of the survey design specifications and accomplishes the appropriate analysis. This customized SAS program can be employed, with minor editing, to analyze general categorical, repeated measures marginal models on sample surveys with replicate weights. Finally, the results of our analysis accounting for the survey design are compared to the results of two alternate analyses of the same data. This comparison confirms that such alternate analyses, which do not properly account for the design, do not produce useful results.

  14. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    Science.gov (United States)

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol. Copyright © 2014. Published by Elsevier Ireland Ltd.

  15. Establishing column batch repeatability according to Quality by Design (QbD) principles using modeling software.

    Science.gov (United States)

    Rácz, Norbert; Kormány, Róbert; Fekete, Jenő; Molnár, Imre

    2015-04-10

    Column technology needs further improvement even today. To get information of batch-to-batch repeatability, intelligent modeling software was applied. Twelve columns from the same production process, but from different batches were compared in this work. In this paper, the retention parameters of these columns with real life sample solutes were studied. The following parameters were selected for measurements: gradient time, temperature and pH. Based on calculated results, batch-to-batch repeatability of BEH columns was evaluated. Two parallel measurements on two columns from the same batch were performed to obtain information about the quality of packing. Calculating the average of individual working points at the highest critical resolution (R(s,crit)) it was found that the robustness, calculated with a newly released robustness module, had a success rate >98% among the predicted 3(6) = 729 experiments for all 12 columns. With the help of retention modeling all substances could be separated independently from the batch and/or packing, using the same conditions, having high robustness of the experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Using Computational and Mechanical Models to Study Animal Locomotion

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  18. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    Directory of Open Access Journals (Sweden)

    Gyula Varadi

    2015-01-01

    Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

  19. Zebrafish: an animal model for research in veterinary medicine.

    Science.gov (United States)

    Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J

    2015-01-01

    The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic

  20. Fuzzy classification of phantom parent groups in an animal model

    Directory of Open Access Journals (Sweden)

    Fikse Freddy

    2009-09-01

    Full Text Available Abstract Background Genetic evaluation models often include genetic groups to account for unequal genetic level of animals with unknown parentage. The definition of phantom parent groups usually includes a time component (e.g. years. Combining several time periods to ensure sufficiently large groups may create problems since all phantom parents in a group are considered contemporaries. Methods To avoid the downside of such distinct classification, a fuzzy logic approach is suggested. A phantom parent can be assigned to several genetic groups, with proportions between zero and one that sum to one. Rules were presented for assigning coefficients to the inverse of the relationship matrix for fuzzy-classified genetic groups. This approach was illustrated with simulated data from ten generations of mass selection. Observations and pedigree records were randomly deleted. Phantom parent groups were defined on the basis of gender and generation number. In one scenario, uncertainty about generation of birth was simulated for some animals with unknown parents. In the distinct classification, one of the two possible generations of birth was randomly chosen to assign phantom parents to genetic groups for animals with simulated uncertainty, whereas the phantom parents were assigned to both possible genetic groups in the fuzzy classification. Results The empirical prediction error variance (PEV was somewhat lower for fuzzy-classified genetic groups. The ranking of animals with unknown parents was more correct and less variable across replicates in comparison with distinct genetic groups. In another scenario, each phantom parent was assigned to three groups, one pertaining to its gender, and two pertaining to the first and last generation, with proportion depending on the (true generation of birth. Due to the lower number of groups, the empirical PEV of breeding values was smaller when genetic groups were fuzzy-classified. Conclusion Fuzzy

  1. Aggression, Social Stress, and the Immune System in Humans and Animal Models

    Directory of Open Access Journals (Sweden)

    Aki Takahashi

    2018-03-01

    Full Text Available Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression.

  2. Aggression, Social Stress, and the Immune System in Humans and Animal Models.

    Science.gov (United States)

    Takahashi, Aki; Flanigan, Meghan E; McEwen, Bruce S; Russo, Scott J

    2018-01-01

    Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression.

  3. Utility of Small Animal Models of Developmental Programming.

    Science.gov (United States)

    Reynolds, Clare M; Vickers, Mark H

    2018-01-01

    Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.

  4. Establishment of animal model with half-liver cirrhosis

    International Nuclear Information System (INIS)

    Yang Zhenghan; Zhou Cheng; Chen Min; Xie Jingxia; Zhang Yuewu; Hu Bifang; Mo Hongbo; Wu Xiao

    2003-01-01

    Objective: To establish a new cirrhosis model suitable for imaging study. Methods: Via a 4 F catheter, 50-100 μl of carbon tetrachloride was injected into the left or right hepatic artery of 12 dogs fortnightly. Liver functional test, imaging study, and pathological examination were performed in these dogs regularly. Results: As the times of injection increased, necrosis of hepatocytes, fibrosis, and cirrhosis of the liver aggravated. In each dog, cirrhosis was more serious in the half liver with carbon tetrachloride injection than in the other half liver without carbon tetrachloride injection. With this model, it was convenient to perform the imaging study of liver cirrhosis. Conclusion: Animal model with half-liver cirrhosis can be established by combining catheter technique and traditional method

  5. Three-dimensional temporomandibular joint modeling and animation.

    Science.gov (United States)

    Cascone, Piero; Rinaldi, Fabrizio; Pagnoni, Mario; Marianetti, Tito Matteo; Tedaldi, Massimiliano

    2008-11-01

    The three-dimensional (3D) temporomandibular joint (TMJ) model derives from a study of the cranium by 3D virtual reality and mandibular function animation. The starting point of the project is high-fidelity digital acquisition of a human dry skull. The cooperation between the maxillofacial surgeon and the cartoonist enables the reconstruction of the fibroconnective components of the TMJ that are the keystone for comprehension of the anatomic and functional features of the mandible. The skeletal model is customized with the apposition of the temporomandibular ligament, the articular disk, the retrodiskal tissue, and the medial and the lateral ligament of the disk. The simulation of TMJ movement is the result of the integration of up-to-date data on the biomechanical restrictions. The 3D TMJ model is an easy-to-use application that may be run on a personal computer for the study of the TMJ and its biomechanics.

  6. Using animal models to study post-partum psychiatric disorders.

    Science.gov (United States)

    Perani, C V; Slattery, D A

    2014-10-01

    The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. © 2014 The British Pharmacological Society.

  7. Hepatoprotective activity of Musa paradisiaca on experimental animal models.

    Science.gov (United States)

    Nirmala, M; Girija, K; Lakshman, K; Divya, T

    2012-01-01

    To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

  8. A novel animal model for hyperdynamic airway collapse.

    Science.gov (United States)

    Tsukada, Hisashi; O'Donnell, Carl R; Garland, Robert; Herth, Felix; Decamp, Malcolm; Ernst, Armin

    2010-12-01

    Tracheobronchomalacia (TBM) is increasingly recognized as a condition associated with significant pulmonary morbidity. However, treatment is invasive and complex, and because there is no appropriate animal model, novel diagnostic and treatment strategies are difficult to evaluate. We endeavored to develop a reliable airway model to simulate hyperdynamic airway collapse in humans. Seven 20-kg male sheep were enrolled in this study. Tracheomalacia was created by submucosal resection of > 50% of the circumference of 10 consecutive cervical tracheal cartilage rings through a midline cervical incision. A silicone stent was placed in the trachea to prevent airway collapse during recovery. Tracheal collapsibility was assessed at protocol-specific time points by bronchoscopy and multidetector CT imaging while temporarily removing the stent. Esophageal pressure and flow data were collected to assess flow limitation during spontaneous breathing. All animals tolerated the surgical procedure well and were stented without complications. One sheep died at 2 weeks because of respiratory failure related to stent migration. In all sheep, near-total forced inspiratory airway collapse was observed up to 3 months postprocedure. Esophageal manometry demonstrated flow limitation associated with large negative pleural pressure swings during rapid spontaneous inhalation. Hyperdynamic airway collapse can reliably be induced with this technique. It may serve as a model for evaluation of novel diagnostic and therapeutic strategies for TBM.

  9. Steroid-associated osteonecrosis animal model in rats

    Directory of Open Access Journals (Sweden)

    Li-Zhen Zheng

    2018-04-01

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

  10. Group size effects in two repeated game models of a global climate agreement

    Energy Technology Data Exchange (ETDEWEB)

    Helland, Leif

    2002-07-01

    What levels of total abatement can one hope for in a global climate agreement. Some potential answers to this question are provided by game theory. This working paper contains a critical discussion of two (prominent) game ,models that answer the question quite pessimistically. Both models take the n-person, infinitely repeated prisoner's dilemma game as their point of departure. The first model is a full information model and utilises the motion of a weakly re negotiation proof equilibrium. This results in the (maybe counterintuitive) prediction that an agreement that can provide high utility to the group will attract less total abatement than an agreement that can only provide low utility to the group. The second model assumes imperfect public information and utilises the notion of a trigger level equilibrium. This results in the (more intuitive) prediction that the level of total abatements will increase with improved verification techniques for a given player set. Still the level of total abatements decrease with an increasing player set for a given verification technique. Empirical implications of the two models are identified and it is argued that one should confront these with experimentally generated data in order to discriminate between the models. One reason for this is that historical data on abatement efforts in a global climate agreement do not exist since no such agreement has entered into force yet. (Author)

  11. Group size effects in two repeated game models of a global climate agreement

    International Nuclear Information System (INIS)

    Helland, Leif

    2002-01-01

    What levels of total abatement can one hope for in a global climate agreement. Some potential answers to this question are provided by game theory. This working paper contains a critical discussion of two (prominent) game ,models that answer the question quite pessimistically. Both models take the n-person, infinitely repeated prisoner's dilemma game as their point of departure. The first model is a full information model and utilises the motion of a weakly re negotiation proof equilibrium. This results in the (maybe counterintuitive) prediction that an agreement that can provide high utility to the group will attract less total abatement than an agreement that can only provide low utility to the group. The second model assumes imperfect public information and utilises the notion of a trigger level equilibrium. This results in the (more intuitive) prediction that the level of total abatements will increase with improved verification techniques for a given player set. Still the level of total abatements decrease with an increasing player set for a given verification technique. Empirical implications of the two models are identified and it is argued that one should confront these with experimentally generated data in order to discriminate between the models. One reason for this is that historical data on abatement efforts in a global climate agreement do not exist since no such agreement has entered into force yet. (Author)

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Use, misuse and extensions of "ideal gas" models of animal encounter.

    Science.gov (United States)

    Hutchinson, John M C; Waser, Peter M

    2007-08-01

    Biologists have repeatedly rediscovered classical models from physics predicting collision rates in an ideal gas. These models, and their two-dimensional analogues, have been used to predict rates and durations of encounters among animals or social groups that move randomly and independently, given population density, velocity, and distance at which an encounter occurs. They have helped to separate cases of mixed-species association based on behavioural attraction from those that simply reflect high population densities, and to detect cases of attraction or avoidance among conspecifics. They have been used to estimate the impact of population density, speeds of movement and size on rates of encounter between members of the opposite sex, between gametes, between predators and prey, and between observers and the individuals that they are counting. One limitation of published models has been that they predict rates of encounter, but give no means of determining whether observations differ significantly from predictions. Another uncertainty is the robustness of the predictions when animal movements deviate from the model's assumptions in specific, biologically relevant ways. Here, we review applications of the ideal gas model, derive extensions of the model to cover some more realistic movement patterns, correct several errors that have arisen in the literature, and show how to generate confidence limits for expected rates of encounter among independently moving individuals. We illustrate these results using data from mangabey monkeys originally used along with the ideal gas model to argue that groups avoid each other. Although agent-based simulations provide a more flexible alternative approach, the ideal gas model remains both a valuable null model and a useful, less onerous, approximation to biological reality.

  14. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

    Directory of Open Access Journals (Sweden)

    Ami eCohen

    2013-06-01

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

  15. Computer-aided pulmonary image analysis in small animal models

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: ulasbagci@gmail.com [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2015-07-15

    Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Developing the Pieta House Suicide Intervention Model: a quasi-experimental, repeated measures design.

    Science.gov (United States)

    Surgenor, Paul Wg; Freeman, Joan; O'Connor, Cindy

    2015-01-01

    While most crisis intervention models adhere to a generalised theoretical framework, the lack of clarity around how these should be enacted has resulted in a proliferation of models, most of which have little to no empirical support. The primary aim of this research was to propose a suicide intervention model that would resolve the client's suicidal crisis by decreasing their suicidal ideation and improve their outlook through enhancing a range of protective factors. The secondary aim was to assess the impact of this model on negative and positive outlook. A quasi-experimental, pre-test post-test repeated measures design was employed. A questionnaire assessing self-esteem, depression, and positive and negative suicidal ideation was administered to the same participants pre- and post- therapy facilitating paired responses. Multiple analysis of variance and paired-samples t-tests were conducted to establish whether therapy using the PH-SIM had a significant effect on the clients' negative and positive outlook. Analyses revealed a statistically significant effect of therapy for depression, negative suicidal ideation, self-esteem, and positive suicidal ideation. Negative outlook was significantly lower after therapy and positive outlook significantly higher. The decreased negative outlook and increased positive outlook following therapy provide some support for the proposed model in fulfilling its role, though additional research is required to establish the precise role of the intervention model in achieving this.

  18. A Neutron Star-White Dwarf Binary Model for Repeating Fast Radio Burst 121102

    Science.gov (United States)

    Gu, Wei-Min; Dong, Yi-Ze; Liu, Tong; Ma, Renyi; Wang, Junfeng

    2016-06-01

    We propose a compact binary model for the fast radio burst (FRB) repeaters, where the system consists of a magnetic white dwarf (WD) and a neutron star (NS) with strong bipolar magnetic fields. When the WD fills its Roche lobe, mass transfer will occur from the WD to the NS through the inner Lagrange point. The accreted magnetized materials may trigger magnetic reconnection when they approach the NS surface, and therefore the electrons can be accelerated to an ultra-relativistic speed. In this scenario, the curvature radiation of the electrons moving along the NS magnetic field lines can account for the characteristic frequency and the timescale of an FRB. Owing to the conservation of angular momentum, the WD may be kicked away after a burst, and the next burst may appear when the system becomes semi-detached again through the gravitational radiation. By comparing our analyses with the observations, we show that such an intermittent Roche-lobe overflow mechanism can be responsible for the observed repeating behavior of FRB 121102.

  19. A NEUTRON STAR–WHITE DWARF BINARY MODEL FOR REPEATING FAST RADIO BURST 121102

    International Nuclear Information System (INIS)

    Gu, Wei-Min; Dong, Yi-Ze; Liu, Tong; Ma, Renyi; Wang, Junfeng

    2016-01-01

    We propose a compact binary model for the fast radio burst (FRB) repeaters, where the system consists of a magnetic white dwarf (WD) and a neutron star (NS) with strong bipolar magnetic fields. When the WD fills its Roche lobe, mass transfer will occur from the WD to the NS through the inner Lagrange point. The accreted magnetized materials may trigger magnetic reconnection when they approach the NS surface, and therefore the electrons can be accelerated to an ultra-relativistic speed. In this scenario, the curvature radiation of the electrons moving along the NS magnetic field lines can account for the characteristic frequency and the timescale of an FRB. Owing to the conservation of angular momentum, the WD may be kicked away after a burst, and the next burst may appear when the system becomes semi-detached again through the gravitational radiation. By comparing our analyses with the observations, we show that such an intermittent Roche-lobe overflow mechanism can be responsible for the observed repeating behavior of FRB 121102.

  20. A NEUTRON STAR–WHITE DWARF BINARY MODEL FOR REPEATING FAST RADIO BURST 121102

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Wei-Min; Dong, Yi-Ze; Liu, Tong; Ma, Renyi; Wang, Junfeng, E-mail: guwm@xmu.edu.cn [Department of Astronomy, Xiamen University, Xiamen, Fujian 361005 (China)

    2016-06-01

    We propose a compact binary model for the fast radio burst (FRB) repeaters, where the system consists of a magnetic white dwarf (WD) and a neutron star (NS) with strong bipolar magnetic fields. When the WD fills its Roche lobe, mass transfer will occur from the WD to the NS through the inner Lagrange point. The accreted magnetized materials may trigger magnetic reconnection when they approach the NS surface, and therefore the electrons can be accelerated to an ultra-relativistic speed. In this scenario, the curvature radiation of the electrons moving along the NS magnetic field lines can account for the characteristic frequency and the timescale of an FRB. Owing to the conservation of angular momentum, the WD may be kicked away after a burst, and the next burst may appear when the system becomes semi-detached again through the gravitational radiation. By comparing our analyses with the observations, we show that such an intermittent Roche-lobe overflow mechanism can be responsible for the observed repeating behavior of FRB 121102.

  1. The animal model determines the results of Aeromonas virulence factors

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2016-10-01

    Full Text Available The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of A. hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analysed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-1∆vapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild type. Variations between models were evidenced using the AH-1∆rmlB, which lacks the O-antigen lipopolysaccharide (LPS, and the AH-1∆wahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH-1ΔFlaB-J (lacking polar flagella and unable to swim and the AH-1::motX (non-motile but producing flagella. They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study

  2. An Animal Model for Human EBV-Associated Hemophagocytic Syndrome

    Science.gov (United States)

    Hayashi, Kazuhiko; Ohara, Nobuya; Teramoto, Norihiro; Onoda, Sachiyo; Chen, Hong-Li; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Yates, John; Akagi, Tadaatsu

    2001-01-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS. PMID:11290571

  3. Experimental animal data and modeling of late somatic effects

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1988-01-01

    This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable

  4. Immune-mediated animal models of Tourette syndrome

    Science.gov (United States)

    Hornig, Mady; Lipkin, W. Ian

    2014-01-01

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

  5. Can animal models contribute to understanding tinnitus heterogeneity in humans?

    Directory of Open Access Journals (Sweden)

    Jos J Eggermont

    2016-11-01

    Full Text Available The brain activity of humans with tinnitus of various etiologies is typically studied with EEG/MEG and fMRI-based imaging techniques. Consequently, they measure population responses and mostly from the neocortex. The latter also underlies changes in neural networks that may be attributed to tinnitus. However, factors not strictly related to tinnitus such as hearing loss and hyperacusis, as well as other co-occurring disorders play a prominent role in these changes. Different types of tinnitus can often not be resolved with these brain-imaging techniques. In animal models of putative behavioral signs of tinnitus, neural activity ranging from auditory nerve to auditory cortex, is studied largely by single unit recordings, augmented by local field potentials (LFPs, and the neural correlates of tinnitus are mainly based on spontaneous neural activity, such as spontaneous firing rates (SFR and pair-wise spontaneous spike-firing correlations. Neural correlates of hyperacusis rely on measurement of stimulus-evoked activity and are measured as increased driven firing rates and LFP amplitudes. Connectivity studies would rely on correlated neural activity between pairs of neurons or LFP amplitudes, but are only recently explored. In animal models of tinnitus only two etiologies are extensively studied; tinnitus evoked by salicylate application and by noise exposure. It appears that they have quite different neural biomarkers. The unanswered question then is: does this different etiology also result in different tinnitus?

  6. An intermediate animal model of spinal cord stimulation

    Directory of Open Access Journals (Sweden)

    Thomas Guiho

    2016-06-01

    Full Text Available Spinal cord injuries (SCI result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self- catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.

  7. Dissecting OCD Circuits: From Animal Models to Targeted Treatments

    Science.gov (United States)

    Ahmari, Susanne E.; Dougherty, Darin D.

    2015-01-01

    Obsessive Compulsive Disorder (OCD) is a chronic, severe mental illness with up to 2–3% prevalence worldwide, which has been classified as one of the world’s 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms 1. Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. PMID:25952989

  8. An analysis of single amino acid repeats as use case for application specific background models

    Directory of Open Access Journals (Sweden)

    Sykacek Peter

    2011-05-01

    Full Text Available Abstract Background Sequence analysis aims to identify biologically relevant signals against a backdrop of functionally meaningless variation. Increasingly, it is recognized that the quality of the background model directly affects the performance of analyses. State-of-the-art approaches rely on classical sequence models that are adapted to the studied dataset. Although performing well in the analysis of globular protein domains, these models break down in regions of stronger compositional bias or low complexity. While these regions are typically filtered, there is increasing anecdotal evidence of functional roles. This motivates an exploration of more complex sequence models and application-specific approaches for the investigation of biased regions. Results Traditional Markov-chains and application-specific regression models are compared using the example of predicting runs of single amino acids, a particularly simple class of biased regions. Cross-fold validation experiments reveal that the alternative regression models capture the multi-variate trends well, despite their low dimensionality and in contrast even to higher-order Markov-predictors. We show how the significance of unusual observations can be computed for such empirical models. The power of a dedicated model in the detection of biologically interesting signals is then demonstrated in an analysis identifying the unexpected enrichment of contiguous leucine-repeats in signal-peptides. Considering different reference sets, we show how the question examined actually defines what constitutes the 'background'. Results can thus be highly sensitive to the choice of appropriate model training sets. Conversely, the choice of reference data determines the questions that can be investigated in an analysis. Conclusions Using a specific case of studying biased regions as an example, we have demonstrated that the construction of application-specific background models is both necessary and

  9. Animal Models of Lymphangioleiomyomatosis (LAM) and Tuberous Sclerosis Complex (TSC)

    Science.gov (United States)

    2010-01-01

    Abstract Animal models of lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC) are highly desired to enable detailed investigation of the pathogenesis of these diseases. Multiple rats and mice have been generated in which a mutation similar to that occurring in TSC patients is present in an allele of Tsc1 or Tsc2. Unfortunately, these mice do not develop pathologic lesions that match those seen in LAM or TSC. However, these Tsc rodent models have been useful in confirming the two-hit model of tumor development in TSC, and in providing systems in which therapeutic trials (e.g., rapamycin) can be performed. In addition, conditional alleles of both Tsc1 and Tsc2 have provided the opportunity to target loss of these genes to specific tissues and organs, to probe the in vivo function of these genes, and attempt to generate better models. Efforts to generate an authentic LAM model are impeded by a lack of understanding of the cell of origin of this process. However, ongoing studies provide hope that such a model will be generated in the coming years. PMID:20235887

  10. Modeling warfare in social animals: a "chemical" approach.

    Science.gov (United States)

    Santarlasci, Alisa; Martelloni, Gianluca; Frizzi, Filippo; Santini, Giacomo; Bagnoli, Franco

    2014-01-01

    We present here a general method for modelling the dynamics of battles among social animals. The proposed method exploits the procedures widely used to model chemical reactions, but still uncommon in behavioural studies. We applied this methodology to the interpretation of experimental observations of battles between two species of ants (Lasius neglectus and Lasius paralienus), but this scheme may have a wider applicability and can be extended to other species as well. We performed two types of experiment labelled as interaction and mortality. The interaction experiments are designed to obtain information on the combat dynamics and lasted one hour. The mortality ones provide information on the casualty rates of the two species and lasted five hours. We modelled the interactions among ants using a chemical model which considers the single ant individuals and fighting groups analogously to atoms and molecules. The mean-field behaviour of the model is described by a set of non-linear differential equations. We also performed stochastic simulations of the corresponding agent-based model by means of the Gillespie event-driven integration scheme. By fitting the stochastic trajectories with the deterministic model, we obtained the probability distribution of the reaction parameters. The main result that we obtained is a dominance phase diagram, that gives the average trajectory of a generic battle, for an arbitrary number of opponents. This phase diagram was validated with some extra experiments. With respect to other war models (e.g., Lanchester's ones), our chemical model considers all phases of the battle and not only casualties. This allows a more detailed description of the battle (with a larger number of parameters), allowing the development of more sophisticated models (e.g., spatial ones), with the goal of distinguishing collective effects from the strategic ones.

  11. Modeling Warfare in Social Animals: A "Chemical" Approach

    Science.gov (United States)

    Santarlasci, Alisa; Martelloni, Gianluca; Frizzi, Filippo; Santini, Giacomo; Bagnoli, Franco

    2014-01-01

    We present here a general method for modelling the dynamics of battles among social animals. The proposed method exploits the procedures widely used to model chemical reactions, but still uncommon in behavioural studies. We applied this methodology to the interpretation of experimental observations of battles between two species of ants (Lasius neglectus and Lasius paralienus), but this scheme may have a wider applicability and can be extended to other species as well. We performed two types of experiment labelled as interaction and mortality. The interaction experiments are designed to obtain information on the combat dynamics and lasted one hour. The mortality ones provide information on the casualty rates of the two species and lasted five hours. We modelled the interactions among ants using a chemical model which considers the single ant individuals and fighting groups analogously to atoms and molecules. The mean-field behaviour of the model is described by a set of non-linear differential equations. We also performed stochastic simulations of the corresponding agent-based model by means of the Gillespie event-driven integration scheme. By fitting the stochastic trajectories with the deterministic model, we obtained the probability distribution of the reaction parameters. The main result that we obtained is a dominance phase diagram, that gives the average trajectory of a generic battle, for an arbitrary number of opponents. This phase diagram was validated with some extra experiments. With respect to other war models (e.g., Lanchester's ones), our chemical model considers all phases of the battle and not only casualties. This allows a more detailed description of the battle (with a larger number of parameters), allowing the development of more sophisticated models (e.g., spatial ones), with the goal of distinguishing collective effects from the strategic ones. PMID:25369269

  12. Modeling warfare in social animals: a "chemical" approach.

    Directory of Open Access Journals (Sweden)

    Alisa Santarlasci

    Full Text Available We present here a general method for modelling the dynamics of battles among social animals. The proposed method exploits the procedures widely used to model chemical reactions, but still uncommon in behavioural studies. We applied this methodology to the interpretation of experimental observations of battles between two species of ants (Lasius neglectus and Lasius paralienus, but this scheme may have a wider applicability and can be extended to other species as well. We performed two types of experiment labelled as interaction and mortality. The interaction experiments are designed to obtain information on the combat dynamics and lasted one hour. The mortality ones provide information on the casualty rates of the two species and lasted five hours. We modelled the interactions among ants using a chemical model which considers the single ant individuals and fighting groups analogously to atoms and molecules. The mean-field behaviour of the model is described by a set of non-linear differential equations. We also performed stochastic simulations of the corresponding agent-based model by means of the Gillespie event-driven integration scheme. By fitting the stochastic trajectories with the deterministic model, we obtained the probability distribution of the reaction parameters. The main result that we obtained is a dominance phase diagram, that gives the average trajectory of a generic battle, for an arbitrary number of opponents. This phase diagram was validated with some extra experiments. With respect to other war models (e.g., Lanchester's ones, our chemical model considers all phases of the battle and not only casualties. This allows a more detailed description of the battle (with a larger number of parameters, allowing the development of more sophisticated models (e.g., spatial ones, with the goal of distinguishing collective effects from the strategic ones.

  13. On modeling animal movements using Brownian motion with measurement error.

    Science.gov (United States)

    Pozdnyakov, Vladimir; Meyer, Thomas; Wang, Yu-Bo; Yan, Jun

    2014-02-01

    Modeling animal movements with Brownian motion (or more generally by a Gaussian process) has a long tradition in ecological studies. The recent Brownian bridge movement model (BBMM), which incorporates measurement errors, has been quickly adopted by ecologists because of its simplicity and tractability. We discuss some nontrivial properties of the discrete-time stochastic process that results from observing a Brownian motion with added normal noise at discrete times. In particular, we demonstrate that the observed sequence of random variables is not Markov. Consequently the expected occupation time between two successively observed locations does not depend on just those two observations; the whole path must be taken into account. Nonetheless, the exact likelihood function of the observed time series remains tractable; it requires only sparse matrix computations. The likelihood-based estimation procedure is described in detail and compared to the BBMM estimation.

  14. What We Have Learned from Animal Models of Dry Eye

    Science.gov (United States)

    Stern, Michael E.; Pflugfelder, Stephen C.

    2017-01-01

    Animal models have proved valuable to investigate the pathogenesis of dry eye disease, identify therapeutic targets and the efficacy of candidate therapeutics for dry eye. Pharmacological inhibition of the lacrimal functional unit and exposure of the mouse eye to desiccating stress was found to activate innate immune pathways, promote dendritic cell maturation and initiate an adaptive T cell response to ocular surface antigens. Disease relevant mediators and pathways have been identified through use of genetically altered mice, specific inhibitors and adoptive transfer of desiccating stress primed CD4+ T cells to naïve recipients. Findings from mouse models have elucidated the mechanism of action of cyclosporine A and the rationale for developing lifitegrast, the two currently approved therapeutics in the US. PMID:28282318

  15. Shopping Centers as Panther Habitat: Inferring Animal Locations from Models

    Directory of Open Access Journals (Sweden)

    David S. Maehr

    2004-12-01

    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.

  16. Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model.

    Science.gov (United States)

    Chakraborty, Nabarun; Meyerhoff, James; Jett, Marti; Hammamieh, Rasha

    2017-01-01

    Post-traumatic stress disorder (PTSD) is a debilitating illness that imposes significant emotional and financial burdens on military families. The understanding of PTSD etiology remains elusive; nonetheless, it is clear that PTSD is manifested by a cluster of symptoms including hyperarousal, reexperiencing of traumatic events, and avoidance of trauma reminders. With these characteristics in mind, several rodent models have been developed eliciting PTSD-like features. Animal models with social dimensions are of particular interest, since the social context plays a major role in the development and manifestation of PTSD.For civilians, a core trauma that elicits PTSD might be characterized by a singular life-threatening event such as a car accident. In contrast, among war veterans, PTSD might be triggered by repeated threats and a cumulative psychological burden that coalesced in the combat zone. In capturing this fundamental difference, the aggressor-exposed social stress (Agg-E SS) model imposes highly threatening conspecific trauma on naïve mice repeatedly and randomly.There is abundant evidence that suggests the potential role of genetic contributions to risk factors for PTSD. Specific observations include putatively heritable attributes of the disorder, the cited cases of atypical brain morphology, and the observed neuroendocrine shifts away from normative. Taken together, these features underscore the importance of multi-omics investigations to develop a comprehensive picture. More daunting will be the task of downstream analysis with integration of these heterogeneous genotypic and phenotypic data types to deliver putative clinical biomarkers. Researchers are advocating for a systems biology approach, which has demonstrated an increasingly robust potential for integrating multidisciplinary data. By applying a systems biology approach here, we have connected the tissue-specific molecular perturbations to the behaviors displayed by mice subjected to Agg-E SS. A

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

    Czech Academy of Sciences Publication Activity Database

    Svojanovská, Markéta; Stuchlík, Aleš

    2015-01-01

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

  18. Mechanisms Involved in Secondary Cardiac Dysfunction in Animal Models of Trauma and Hemorrhagic Shock.

    Science.gov (United States)

    Wilson, Nick M; Wall, Johanna; Naganathar, Veena; Brohi, Karim; De'Ath, Henry D

    2017-10-01

    Clinical evidence reveals the existence of a trauma-induced secondary cardiac injury (TISCI) that is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma hemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-like receptors, the exact protagonists of which remain unclear. Shortly following trauma and hemorrhage, cardiomyocytes upregulate gene regulatory protein and inflammatory molecule expression including nuclear factor kappa beta, tumor necrosis factor alpha, and interleukin-6. This is associated with expression of membrane bound adhesion molecules and chemokines leading to marked myocardial leukocyte infiltration. This cell activation and infiltration is linked to a rise in enzymes that cause oxidative and nitrative stress and subsequent protein misfolding within cardiomyocytes. Such protein damage may lead to reduced contractility and myocyte apoptosis. Other molecules have been identified as cardioprotective following injury. These include p38 mitogen-activated protein kinases and heat shock proteins.The balance between increasing damaging mediators and a reduction in cardio-protective molecules appears to define myocardial function following trauma. Exogenous therapeutics have been trialled in rodents with promising abilities to favorably alter this balance, and subsequently lead to improved cardiac function.

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

    Science.gov (United States)

    Cai, Bin; Wang, Ning

    2016-01-01

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

  20. An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.

    Science.gov (United States)

    Bozeman, Andrew P; Dassinger, Melvin S; Birusingh, Rhea J; Burford, Jeffrey M; Smith, Samuel D

    2013-04-01

    Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

  1. Estimating the Prevalence of Atrial Fibrillation from A Three-Class Mixture Model for Repeated Diagnoses

    Science.gov (United States)

    Li, Liang; Mao, Huzhang; Ishwaran, Hemant; Rajeswaran, Jeevanantham; Ehrlinger, John; Blackstone, Eugene H.

    2016-01-01

    Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular heart beat, with or without perceivable symptoms. In clinical practice, the electrocardiogram (ECG) is often used for diagnosis of AF. Since the AF often arrives as recurrent episodes of varying frequency and duration and only the episodes that occur at the time of ECG can be detected, the AF is often underdiagnosed when a limited number of repeated ECGs are used. In studies evaluating the efficacy of AF ablation surgery, each patient undergo multiple ECGs and the AF status at the time of ECG is recorded. The objective of this paper is to estimate the marginal proportions of patients with or without AF in a population, which are important measures of the efficacy of the treatment. The underdiagnosis problem is addressed by a three-class mixture regression model in which a patient’s probability of having no AF, paroxysmal AF, and permanent AF is modeled by auxiliary baseline covariates in a nested logistic regression. A binomial regression model is specified conditional on a subject being in the paroxysmal AF group. The model parameters are estimated by the EM algorithm. These parameters are themselves nuisance parameters for the purpose of this research, but the estimators of the marginal proportions of interest can be expressed as functions of the data and these nuisance parameters and their variances can be estimated by the sandwich method. We examine the performance of the proposed methodology in simulations and two real data applications. PMID:27983754

  2. Caisson disease of bone: a study of the Göttingen mini-pig as an animal model.

    Science.gov (United States)

    Gregg, P J; Walder, D N; Rannie, I

    1980-02-01

    Investigation of the exact aetiology, early diagnosis and prevention of caisson disease of bone has been hindered by the inability to produce, by the use of realistic compression/decompression exposures, truly comparable lesions in animals. Four Gottingen mini-pigs were subjected to repeated exposures to pressures of 27 p.s.i.g. for 6 h over a period of 9 months and decompressed according to standard tables. Two mini-pigs acted as controls. In one animal radiological changes were recognised in the left lower femoral shaft 19 weeks after the exposures were started and subsequent examination of that bone confirmed the presence, at that site, of a lesion which macroscopically and microscopically resembled, in every way, the appearances of those seen in the shafts of long bones in man. It is concluded therefore that, properly used, the mini-pig may be a suitable animal model for the study of this condition in man.

  3. Antithrombin III in animal models of sepsis and organ failure.

    Science.gov (United States)

    Dickneite, G

    1998-01-01

    Antithrombin III (AT III) is the physiological inhibitor of thrombin and other serine proteases of the clotting cascade. In the development of sepsis, septic shock and organ failure, the plasma levels of AT III decrease considerably, suggesting the concept of a substitution therapy with the inhibitor. A decrease of AT III plasma levels might also be associated with other pathological disorders like trauma, burns, pancreatitis or preclampsia. Activation of coagulation and consumption of AT III is the consequence of a generalized inflammation called SIRS (systemic inflammatory response syndrome). The clotting cascade is also frequently activated after organ transplantation, especially if organs are grafted between different species (xenotransplantation). During the past years AT III has been investigated in numerous corresponding disease models in different animal species which will be reviewed here. The bulk of evidence suggests, that AT III substitution reduces morbidity and mortality in the diseased animals. While gaining more experience with AT III, the concept of substitution therapy to maximal baseline plasma levels (100%) appears to become insufficient. Evidence from clinical and preclinical studies now suggests to adjust the AT III plasma levels to about 200%, i.e., doubling the normal value. During the last few years several authors proposed that AT III might not only be an anti-thrombotic agent, but to have in addition an anti-inflammatory effect.

  4. Animal model of rapid crystalloid infusion in rats

    Directory of Open Access Journals (Sweden)

    Flavio Stillitano Orgaes

    2013-04-01

    Full Text Available PURPOSE: To describe an animal model of rapid intravenous infusion with different volumes of crystalloid and discuss the clinical findings. METHODS: Fifty six male Wistar rats were used, divided randomly in seven groups (n = 8. The rats of groups 1 to 6 received lactated Ringer´s solution intravenously, in the rate of 25 ml/min, with different volumes proportional to blood volume (BV. The rats of group 0 were submitted to the same procedure, but did not receive the fluid (control group. The data included respiratory rate, heart rate, saturation of peripheral oxygen (SpO2 in two times (before and after the infusion, and upshots (respiratory arrest and death. Dunnett´s test and ANOVA were used. RESULTS: The clinical signs significantly changed in the 2, 2.5 and 3 fold BV groups. The respiratory arrest was observed in the 1.5, 2, 2.5 and 3 fold BV groups, but death was present only in 2.5 and 3 fold BV groups. CONCLUSIONS: The infusion of crystalloid in the same volume of blood volume did not cause significant variation in respiratory and heart rate, saturation of peripheral oxygen and did not induce respiratory arrest. The infusion of a volume of 3 fold blood volume was lethal to all animals.

  5. Chronic and acute effects of stress on energy balance: are there appropriate animal models?

    Science.gov (United States)

    Harris, Ruth B S

    2015-02-15

    Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

  6. Graphic-based musculoskeletal model for biomechanical analyses and animation.

    Science.gov (United States)

    Chao, Edmund Y S

    2003-04-01

    The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the 'Virtual Human' reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.

  7. Lessons from Animal Models of Cytoplasmic Intermediate Filament Proteins.

    Science.gov (United States)

    Bouameur, Jamal-Eddine; Magin, Thomas M

    Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies. Epidermal keratins, together with desmin, are essential to protect corresponding tissues against mechanical force but also participate in stabilizing cell adhesion and in inflammatory signalling. Surprisingly, other IF proteins contribute to tissue integrity to a much lesser extent than anticipated, pointing towards their role in stress situations. In support, the overexpression of small chaperones or the interference with inflammatory signalling in several settings has been shown to rescue severe tissue pathologies that resulted from the expression of mutant IF proteins. It stills remains an open issue whether the wide range of IF disorders share similar pathomechanisms. Moreover, we lack an understanding how IF proteins participate in signalling processes. Now, with a large number of mouse models in hand, the next challenge will be to develop organotypic cell culture models to dissect pathomechanisms at the molecular level, to employ Crispr/Cas-mediated genome engineering to optimize models and, finally, to combine available animal models with medicinal chemistry for the development of molecular therapies.

  8. Immunological gap in the infectious animal model for biliary atresia.

    Science.gov (United States)

    Czech-Schmidt, G; Verhagen, W; Szavay, P; Leonhardt, J; Petersen, C

    2001-11-01

    Extrahepatic biliary atresia (EHBA), the etiology of which still remains unclear, occurs exclusively in newborns and has recently been simulated in an animal model. It is possible to trigger an EHBA corresponding to the human disease by means of intraperitoneal infection of newborn Balb/c mice with rhesus rotavirus (RRV). The aim of the present study was to determine the conditions and circumstances for inducing biliary atresia in this model focusing on first-line immunological aspects. Newborn as well as pregnant Balb/c mice were intraperitoneally infected with RRV. The highest incidence of cholestasis (86%) was achieved by infection with 10(6) PFU/ml RRV within the first 12 h postpartum, resulting in EHBA with a lethality of 100%. However, the later the newborn mouse is infected, the less likelihood there is that EHBA is triggered. Additionally, the incidence of biliary atresia in this model depends on the quantity of the virus that is given intraperitoneally. However, the development of biliary atresia is not correlated to the virus in the liver. The antepartum infection of pregnant mice does not induce EHBA in the offspring. Female mice that are immunized against RRV protect their newborns from developing RRV-induced cholestasis and EHBA. This protection is transmitted transplacentally and not by breast milk. It is obvious that a temporary immunological gap is essential for virally induced EHBA. Further studies should focus on specific parameters of the immune system of newborn mice in this biliary atresia model. Copyright 2001 Academic Press.

  9. An animal model of tinnitus: a decade of development.

    Science.gov (United States)

    Jastreboff, P J; Sasaki, C T

    1994-01-01

    Although tinnitus affects approximately 9 million people in the United States, a cure remains elusive and the mechanisms of its origin are speculative. The crucial obstacle in tinnitus research has been the lack of an animal model. Over the last decade we have been creating such a model by combining a variety of methodologies, including a behavioral component, to allow for the detection of tinnitus perception. Initially, 2-deoxyglucose had been used to map changes in the metabolic activity after unilateral destruction of the cochlea. It has been found that the initial decrease of the metabolic rate in the auditory nuclei recovered to preoperative values, which could be attributable to the development of tinnitus. The spontaneous activity of single units recorded from the inferior colliculus before and after salicylate administration revealed an increase of discharges, which might reflect the presence of salicylate-induced tinnitus. Recent data have confirmed, and further elaborated this observation, including the discovery of abnormal, epileptic-like, neuronal activity. Finally, the authors have developed a behavioral model of tinnitus, tested it extensively, and used it to measure tinnitus pitch and loudness. The model is presently used for investigating the hypotheses for the mechanisms of tinnitus.

  10. Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy

    Directory of Open Access Journals (Sweden)

    Li X

    2017-01-01

    Full Text Available Xiang Li,1,2 Guangsheng Li,1,3 Keith Dip-Kei Luk,1 Yong Hu1–3 1Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, 2Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 3Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China Background: Cervical spondylotic myelopathy (CSM is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model. Materials and methods: A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1; CSM model with 4-week chronic compression (group 2, 2 weeks (group 3 and 4 weeks (group 4 after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs. Neuropathological change was evaluated by histological examinations. Results: MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52, ladder rung walking test (p < 0.05, F = 14.21 and latencies (p < 0.05, F = 5.76 and amplitudes (p < 0.05, F = 3.8 of

  11. Mechanisms and genes in human strial presbycusis from animal models.

    Science.gov (United States)

    Ohlemiller, Kevin K

    2009-06-24

    Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1(B-lt) mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23(CAST), CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyr(c-2J), BALB/cJ, CBA/CaJ, NOD.NON-H2(nbl)/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyr(c-2J) mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2(nbl) mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse

  12. Haematological and biochemical effects of polyphenolics in animal models.

    Science.gov (United States)

    Gnanamani, Arumugam; Sudha, Munusamy; Deepa, G; Sudha, M; Deivanai, K; Sadulla, S

    2008-07-01

    Polyphenols of natural and synthetic origin are exploited in tanning sector to convert putrescible skin/hide to non-putrescible leather. However, only 30-40% of the inputs have been taken up for processing, the remaining is released as unspent. The existing conventional wastewater treatment systems are inefficient in removing or degrading these unspent polyphenols and thus detrimental to ecosystem. The present study demonstrates the evaluation of impact of both synthetic and natural polyphenols on biochemical and haematological properties of blood and serum in animal models. The results reveal that concentrations of polyphenols play a major role. At higher concentrations, irrespective of their nature, there was a marked change in the lipid profile (81% reduction), followed by insignificant change in glucose levels, RBC and WBC counts and other haematological parameters. At lower concentrations, no significant changes in the above said properties were observed.

  13. Sound preference test in animal models of addicts and phobias.

    Science.gov (United States)

    Soga, Ryo; Shiramatsu, Tomoyo I; Kanzaki, Ryohei; Takahashi, Hirokazu

    2016-08-01

    Biased or too strong preference for a particular object is often problematic, resulting in addiction and phobia. In animal models, alternative forced-choice tasks have been routinely used, but such preference test is far from daily situations that addicts or phobic are facing. In the present study, we developed a behavioral assay to evaluate the preference of sounds in rodents. In the assay, several sounds were presented according to the position of free-moving rats, and quantified the sound preference based on the behavior. A particular tone was paired with microstimulation to the ventral tegmental area (VTA), which plays central roles in reward processing, to increase sound preference. The behaviors of rats were logged during the classical conditioning for six days. Consequently, some behavioral indices suggest that rats search for the conditioned sound. Thus, our data demonstrated that quantitative evaluation of preference in the behavioral assay is feasible.

  14. Anti-inflammatory activity of Heliotropium strigosum in animal models.

    Science.gov (United States)

    Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

    2015-12-01

    The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models. © The Author(s) 2012.

  15. A large animal model for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Moore, M.P.; Griebenow, M.L.

    1992-01-01

    An epithermal neutron beam is needed to treat relatively deep seated tumors. The scattering characteristics of neutrons in this energy range dictate that in vivo experiments be conducted in a large animal to prevent unacceptable total body irradiation. The canine species has proven an excellent model to evaluate the various problems of boron neutron capture utilizing an epithermal neutron beam. This paper discusses three major components of the authors study: (1) the pharmacokinetics of borocaptate sodium (NA 2 B 12 H 11 SH or BSH) in dogs with spontaneously occurring brain tumors, (2) the radiation tolerance of normal tissues in the dog using an epithermal beam alone and in combination with borocaptate sodium, and (3) initial treatment of dogs with spontaneously occurring brain tumors utilizing borocaptate sodium and an epithermal neutron beam

  16. Pathogenesis of presbycusis in animal models: a review.

    Science.gov (United States)

    Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana

    2011-06-01

    Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

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

  18. Two new animal models for actinide toxicity studies

    International Nuclear Information System (INIS)

    Taylor, G.N.; Gardner, P.A.; Jones, C.W.; Lloyd, R.D.; Mays, C.W.

    1979-01-01

    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

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

    Science.gov (United States)

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

  20. Animated pose templates for modeling and detecting human actions.

    Science.gov (United States)

    Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun

    2014-03-01

    This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a

  1. Faults self-organized by repeated earthquakes in a quasi-static antiplane crack model

    Directory of Open Access Journals (Sweden)

    D. Sornette

    1996-01-01

    Full Text Available We study a 2D quasi-static discrete crack anti-plane model of a tectonic plate with long range elastic forces and quenched disorder. The plate is driven at its border and the load is transferred to all elements through elastic forces. This model can be considered as belonging to the class of self-organized models which may exhibit spontaneous criticality, with four additional ingredients compared to sandpile models, namely quenched disorder, boundary driving, long range forces and fast time crack rules. In this 'crack' model, as in the 'dislocation' version previously studied, we find that the occurrence of repeated earthquakes organizes the activity on well-defined fault-like structures. In contrast with the 'dislocation' model, after a transient, the time evolution becomes periodic with run-aways ending each cycle. This stems from the 'crack' stress transfer rule preventing criticality to organize in favour of cyclic behaviour. For sufficiently large disorder and weak stress drop, these large events are preceded by a complex spacetime history of foreshock activity, characterized by a Gutenberg-Richter power law distribution with universal exponent B = 1±0.05. This is similar to a power law distribution of small nucleating droplets before the nucleation of the macroscopic phase in a first-order phase transition. For large disorder and large stress drop, and for certain specific initial disorder configurations, the stress field becomes frustrated in fast time: out-of-plane deformations (thrust and normal faulting and/or a genuine dynamics must be introduced to resolve this frustration.

  2. The memory state heuristic: A formal model based on repeated recognition judgments.

    Science.gov (United States)

    Castela, Marta; Erdfelder, Edgar

    2017-02-01

    The recognition heuristic (RH) theory predicts that, in comparative judgment tasks, if one object is recognized and the other is not, the recognized one is chosen. The memory-state heuristic (MSH) extends the RH by assuming that choices are not affected by recognition judgments per se, but by the memory states underlying these judgments (i.e., recognition certainty, uncertainty, or rejection certainty). Specifically, the larger the discrepancy between memory states, the larger the probability of choosing the object in the higher state. The typical RH paradigm does not allow estimation of the underlying memory states because it is unknown whether the objects were previously experienced or not. Therefore, we extended the paradigm by repeating the recognition task twice. In line with high threshold models of recognition, we assumed that inconsistent recognition judgments result from uncertainty whereas consistent judgments most likely result from memory certainty. In Experiment 1, we fitted 2 nested multinomial models to the data: an MSH model that formalizes the relation between memory states and binary choices explicitly and an approximate model that ignores the (unlikely) possibility of consistent guesses. Both models provided converging results. As predicted, reliance on recognition increased with the discrepancy in the underlying memory states. In Experiment 2, we replicated these results and found support for choice consistency predictions of the MSH. Additionally, recognition and choice latencies were in agreement with the MSH in both experiments. Finally, we validated critical parameters of our MSH model through a cross-validation method and a third experiment. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Impact of model fat emulsions on sensory perception using repeated spoon to spoon ingestion.

    Science.gov (United States)

    Appelqvist, I A M; Poelman, A A M; Cochet-Broch, M; Delahunty, C M

    2016-06-01

    Eating is a dynamic behaviour, in which food interacts with the mechanical and physiological environment of the mouth. This dynamic interaction changes the oral surfaces leaving particles of food and building up a film on the oral surfaces, which may impact on the temporal perception during the eating experience. The effect of repeated spoon to spoon ingestion of oil in water emulsion products (2%-50% w/w oil) was evaluated using descriptive in-mouth and after swallowing sensory attributes. Descriptive sensory analysis indicated that fatty mouthfeel and afterfeel perception (measured post swallowing) increased with the number of spoonfuls for emulsions containing 50% fat. This effect is likely due to the build-up of oil droplet layers deposited on the mouth surfaces. There was an enhancement of fatty afterfeel intensity for 50% fat emulsions containing the more lipophilic aroma ethylhexanoate compared to ethyl butanoate, indicating a cross-modal interaction. No increase in these attributes from spoon to spoon was observed for the low oil emulsions; since most of the oil in the emulsion was swallowed and very little oil was likely to be left in the mouth. Sweetness perception increased as fat level increased in the emulsion due to an increase in the effective concentration of sugar in the aqueous phase. However, the sweetness perceived did not change from spoon to spoon, suggesting that any oil-droplets deposited on the oral surfaces did not form a complete barrier, restricting access of the sucrose to the taste buds. This study highlights the importance of measuring the dynamic nature of eating and demonstrated change in sensory perception occurring with repeated ingestion of model emulsions, which was likely due to a change in mouth environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model.

    Science.gov (United States)

    Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon; Kang, Hoon

    2016-10-01

    Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia.

  5. Three-dimensional modeler for animated images display system

    International Nuclear Information System (INIS)

    Boubekeur, Rania

    1987-01-01

    The mv3d software allows the modeling and display of three dimensional objects in interpretative mode with animation possibility in real time. This system is intended for a graphical extension of a FORTH interpreter (implemented by CEA/IRDI/D.LETI/DEIN) in order to control a specific hardware (3.D card designed and implemented by DEIN) allowing the generation of three dimensional objects. The object description is carried out with a specific graphical language integrated in the FORTH interpreter. Objects are modeled using elementary solids called basic forms (cube, cone, cylinder...) assembled with classical geometric transformations (rotation, translation and scaling). These basic forms are approximated by plane polygonal facets further divided in triangles. Coordinates of the summits of triangles constitute the geometrical data. These are sent to the 3.D. card for processing and display. Performed processing are: geometrical transformations on display, hidden surface elimination, shading and clipping. The mv3d software is not an entire modeler but a simple, modular and extensible tool, to which other specific functions may be easily added such as: robots motion, collisions... (author) [fr

  6. Common Marmosets: A Potential Translational Animal Model of Juvenile Depression

    Directory of Open Access Journals (Sweden)

    Nicole Leite Galvão-Coelho

    2017-09-01

    Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.

  7. Guinea pigs as an animal model for sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2017-01-01

    Full Text Available The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1 gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2 gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

  8. Animal Models of Autism: An Epigenetic and Environmental Viewpoint

    Directory of Open Access Journals (Sweden)

    Keiko Iwata

    2010-01-01

    Full Text Available Autism is a neurodevelopmental disorder of social behavior, which is more common in males than in females. The causes of autism are unknown; there is evidence for a substantial genetic component, but it is likely that a combination of genetic, environmental and epigenetic factors contribute to its complex pathogenesis. Rodent models that mimic the behavioral deficits of autism can be useful tools for dissecting both the etiology and molecular mechanisms. This review discusses animal models of autism generated by prenatal or neonatal environmental challenges, including virus infection and exposure to valproic acid (VPA or stress. Studies of viral infection models suggest that interleukin-6 can influence fetal development and programming. Prenatal exposure to the histone deacetylase inhibitor VPA has been linked to autism in children, and male VPA-exposed rats exhibit a spectrum of autistic-like behaviors. The experience of prenatal stress produces male-specific behavioral abnormalities in rats. These effects may be mediated by epigenetic modifications such as DNA methylation and histone acetylation resulting in alterations to the transcriptome.

  9. Three-dimensional evaluation of the repeatability of scans of stone models and impressions using a blue LED scanner.

    Science.gov (United States)

    Jeon, Jin-Hun; Jung, Il-Do; Kim, Ji-Hwan; Kim, Hae-Young; Kim, Woong-Chul

    2015-01-01

    In this study, we evaluated the repeatability of scans of stone models and impressions of abutment teeth using a blue LED scanner and compared the findings between different abutment teeth types. For the stone models as well as impression of the canines, premolars, and molars, we generated 10 color-difference-maps and reports for each tooth type (n=10 per tooth type). One-way analysis of variance (ANOVA) and independent t-tests were performed to evaluate the repeatability of scans of the stone models and impressions obtained from a blue LED scanner. Our results indicate a high repeatability of scans of stone models and impressions of abutment teeth using the blue LED scanner and suggest a possible clinical advantage for scanning impressions of different abutment teeth types.

  10. A New Tube Gastrostomy Model in Animal Experiments

    Directory of Open Access Journals (Sweden)

    Atakan Sezer

    2013-01-01

    Full Text Available Aim: The orogastric route is the most preferred application method in the vast majority of the animal experiments in which application can be achieved by adding the material to the water of the experiment animal, through an orogastric tube or with a surgically managed ostomy. Material and Method: This experiment was constructed with twelve male Sprague-Dawley rats which were randomly assigned to one of two groups consist of control group ( group C, n: 6 and tube gastrostomy group ( group TG, n: 6.A novel and simple gastrostomy tube was derivated from a silicone foley catheter. Tube gastrostomy apparatus was constituted with a silicone foley catheter (6 French. In the group TG an incision was performed, and the stomach was visualized. A 1 cm incision was made in the midline and opening of the peritoneum. Anchoring sutures were placed and anterior gastric wall was lifted. The gastric wall is then opened. The apparatus was placed into the stomach and pulled through from a tunnel under the skin and fixed to the lateral abdominal wall with a 2/0 silk suture. Result: The procedure was ended in the 10th day of experiment. No mortality was observed in group C. The rats were monitored daily and no abnormal behavior consists of self harming incision site, resistance to oral intake or attending to displace. There was statistically significant difference in increasing alanine transaminase level (p<0.05 and decrease in the total protein and body weight (p<0.05 at the group TG at the end of experiment. There was significant increase in urea levels in Group C (p<0.05 at the end of experiment. The statistically significant decrease was observed in the same period in group C between aspartate transaminase, albumin, total protein, and body weight (p<0.05.  Glucose (p=0.047 and aspartate transaminase (p=0.050 level decrease changes and weight loose (p=0.034 from preoperative period to the end of the experiment between gastrostomy and laparotomy groups were

  11. Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

    Science.gov (United States)

    Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

    2015-01-01

    Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

  12. Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

    Directory of Open Access Journals (Sweden)

    Cristina eFenollar Ferrer

    2015-09-01

    Full Text Available Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to either the outside or inside of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (asymmetry of these systems has been successfully used as a bioinformatic tool, called repeat-swap modeling to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that

  13. An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

    Science.gov (United States)

    Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

    2015-01-01

    Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

  14. A parsimonious approach to modeling animal movement data.

    Directory of Open Access Journals (Sweden)

    Yann Tremblay

    Full Text Available Animal tracking is a growing field in ecology and previous work has shown that simple speed filtering of tracking data is not sufficient and that improvement of tracking location estimates are possible. To date, this has required methods that are complicated and often time-consuming (state-space models, resulting in limited application of this technique and the potential for analysis errors due to poor understanding of the fundamental framework behind the approach. We describe and test an alternative and intuitive approach consisting of bootstrapping random walks biased by forward particles. The model uses recorded data accuracy estimates, and can assimilate other sources of data such as sea-surface temperature, bathymetry and/or physical boundaries. We tested our model using ARGOS and geolocation tracks of elephant seals that also carried GPS tags in addition to PTTs, enabling true validation. Among pinnipeds, elephant seals are extreme divers that spend little time at the surface, which considerably impact the quality of both ARGOS and light-based geolocation tracks. Despite such low overall quality tracks, our model provided location estimates within 4.0, 5.5 and 12.0 km of true location 50% of the time, and within 9, 10.5 and 20.0 km 90% of the time, for above, equal or below average elephant seal ARGOS track qualities, respectively. With geolocation data, 50% of errors were less than 104.8 km (<0.94 degrees, and 90% were less than 199.8 km (<1.80 degrees. Larger errors were due to lack of sea-surface temperature gradients. In addition we show that our model is flexible enough to solve the obstacle avoidance problem by assimilating high resolution coastline data. This reduced the number of invalid on-land location by almost an order of magnitude. The method is intuitive, flexible and efficient, promising extensive utilization in future research.

  15. Hierarchical modeling of genome-wide Short Tandem Repeat (STR) markers infers native American prehistory.

    Science.gov (United States)

    Lewis, Cecil M

    2010-02-01

    This study examines a genome-wide dataset of 678 Short Tandem Repeat loci characterized in 444 individuals representing 29 Native American populations as well as the Tundra Netsi and Yakut populations from Siberia. Using these data, the study tests four current hypotheses regarding the hierarchical distribution of neutral genetic variation in native South American populations: (1) the western region of South America harbors more variation than the eastern region of South America, (2) Central American and western South American populations cluster exclusively, (3) populations speaking the Chibchan-Paezan and Equatorial-Tucanoan language stock emerge as a group within an otherwise South American clade, (4) Chibchan-Paezan populations in Central America emerge together at the tips of the Chibchan-Paezan cluster. This study finds that hierarchical models with the best fit place Central American populations, and populations speaking the Chibchan-Paezan language stock, at a basal position or separated from the South American group, which is more consistent with a serial founder effect into South America than that previously described. Western (Andean) South America is found to harbor similar levels of variation as eastern (Equatorial-Tucanoan and Ge-Pano-Carib) South America, which is inconsistent with an initial west coast migration into South America. Moreover, in all relevant models, the estimates of genetic diversity within geographic regions suggest a major bottleneck or founder effect occurring within the North American subcontinent, before the peopling of Central and South America. 2009 Wiley-Liss, Inc.

  16. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Elsy Nalleli Loria-Cervera

    2014-01-01

    Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

  17. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Directory of Open Access Journals (Sweden)

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  18. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  19. Cochlear third window in the scala vestibuli: an animal model.

    Science.gov (United States)

    Preis, Michal; Attias, Joseph; Hadar, Tuvia; Nageris, Ben I

    2009-08-01

    Pathologic third window has been investigated in both animals and humans, with a third window located in the vestibular apparatus, specifically, dehiscence of the superior semicircular canal, serving as the clinical model. The present study sought to examine the effect of a cochlear third window in the scala vestibuli on the auditory thresholds in fat sand rats that have a unique anatomy of the inner ear that allows for easy surgical access. The experiment included 7 healthy 6-month-old fat sand rats (a total of 10 ears). A pathologic third window was induced by drilling a hole in the bony labyrinth over the scala vestibuli, with preservation of the membranous labyrinth. Auditory brainstem responses to high- and low-frequency acoustic stimuli delivered via air and bone conduction were recorded before and after the procedure. In the preoperative auditory brainstem response recordings, air-conduction thresholds (ACTs) to clicks and tone bursts averaged 9 and 10 dB, respectively, and bone-conduction thresholds averaged 4.5 and 2.9 dB, respectively. Postfenestration ACTs averaged 41 and 42.2 dB, and bone-conduction thresholds averaged 1.1 and 4.3 dB. The change in ACT was statistically significant (p scala vestibuli affects auditory thresholds by causing a decrease in sensitivity to air-conducted sound stimuli. These findings agree with the theoretical model and clinical findings.

  20. Tocopherol And Tocotrienol: Therapeutic Potential In Animal Models of Stress.

    Science.gov (United States)

    Azlina, Mohd Fahami Nur; Kamisah, Yusof; Qodriyah, Mohd Saad

    2017-11-22

    Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation. The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress. This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Cell and small animal models for phenotypic drug discovery

    Directory of Open Access Journals (Sweden)

    Szabo M

    2017-06-01

    Full Text Available Mihaly Szabo,1 Sara Svensson Akusjärvi,1 Ankur Saxena,1 Jianping Liu,2 Gayathri Chandrasekar,1 Satish S Kitambi1 1Department of Microbiology Tumor, and Cell Biology, 2Department of Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden Abstract: The phenotype-based drug discovery (PDD approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery. Keywords: phenotype, screening, PDD, discovery, zebrafish, drug

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Science.gov (United States)

    Herati, Ramin Sedaghat; Wherry, E John

    2018-04-02

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

  4. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

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

    Science.gov (United States)

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

    2015-07-15

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

  6. The Estimation Modelling of Damaged Areas by Harmful Animals

    Science.gov (United States)

    Jang, R.; Sung, M.; Hwang, J.; Jeon, S. W.

    2017-12-01

    The Republic of Korea has undergone rapid development and urban development without sufficient consideration of the environment. This type of growth is accompanied by a reduction in forest area and wildlife habitat. It is a phenomenon that affects the habitat of large mammals more than small. Especially in Korea, the damage caused by wild boar(Sus scrofa) is harsher than other large mammalian species like water deer(Hydropotes inermis), which also means that the number of these reported cases of this species is higher than ones of other mammals. Wild boar has three to eight cubs per year and it is possible to breed every year, which makes it more populous comparing with the fragmented habitats. It could be regarded as one of the top predators in Korea, which it is inevitable for humans to intervene this creature in population control. In addition, some individuals have been forced to be retreated from other habitats in major habitats, or to invade human activity areas for food activity, thereby destroying crops. Ultimately, this mammal species has been treated as farm pest animals through committing road kills and urban emergences. In this study, we has estimated possible farm pest animal present points from the damage district using 2,505 hazardous wildlife damage areas with four types of geological informations, four kinds of forest information, land cover, and distribution of farmland occurred in Gyeongnam province in Korea. In the estimating model, utilizing MAXENT, information of background point was set to 10,000, 70% of the damaged sites were used to construct the model, 30% was used for verification, and 10 times of crossvalidate were proceeded - verified by AUC of ROC. As a result of analyses, AUC was 0.847, and the percent contribution of the forest information was the distance toward inner-forest areas, 36.1%, the land cover, 16.5%, the distance from the field, 14.9%. Furthermore, the permutation importance was 24.9% of the cover, 12.3% of the height

  7. Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer

    OpenAIRE

    Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R

    2008-01-01

    We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consis...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  9. Modeling the effects of repeated systemic administrations of small activity amounts In radionuclide therapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Cepero, Janet; Colom, Camila; Rodriguez, Juan C.

    2008-01-01

    Full text: Good results for radionuclide therapy treatments where repeated short time spaced systemic injection of small activity amounts are given have been reported. Bone marrow and kidneys are usually considered as dose-limiting organs in radionuclide therapy. The treatments in radionuclide therapy with repeated administration could be optimized if irradiation effects in those one might be estimated. Xeno-grafted mice is the often biological model used during the evaluation of candidates for radionuclide therapy. A mathematical model of tumor cell kinetics was combined with another one reported for marrow cell kinetics which allows the calculation of marrow cell survival and proliferation in response to different irradiation schemes. Radionuclide therapy treatment with repeated administrations with radiopharmaceuticals labeled with beta emitters were simulated. The effects on fast-growing and slow-growing tumors were evaluated, as well as radiosensitive and radioresistant tumors. For more realistic estimation of absorbed dose in mice organs the cross-irradiation due to high energy beta particles was included into the MIRD's formula. Tumor and kidneys responses to the irradiation were estimated on the linear-quadratic model framework which was adapted for a multi-exponential dose rate function describing radionuclide therapy treatments with repeated administrations. Published values for murine tumors kinetics, marrows cellular turnover rates and radiosensitivities were used during the calculations. Iso-effective schemes were also determined varying the interval between fractions and the number of administration. For a given tolerated level of thrombocytopenia and absorbed dose in kidneys an optimal regime of radionuclide therapy with repeated administration could be found. The mathematical model presented here allows the prediction of the nadir and duration of thrombocytopenia, the effects on kidneys and the tumor cell response to various treatment schemes

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

    Science.gov (United States)

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

    2010-01-01

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

  11. Development of computational small animal models and their applications in preclinical imaging and therapy research

    NARCIS (Netherlands)

    Xie, Tianwu; Zaidi, Habib

    The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal

  12. A guinea pig model of acute and chronic asthma using permanently instrumented and unrestrained animals

    NARCIS (Netherlands)

    Meurs, Herman; Santing, Ruud E.; Remie, Rene; van der Mark, Thomas W.; Westerhof, Fiona J.; Zuidhof, Annet B.; Bos, I. Sophie T.; Zaagsma, Johan

    2006-01-01

    To investigate mechanisms underlying allergen-induced asthmatic reactions, airway hyperresponsiveness and remodeling, we have developed a guinea pig model of acute and chronic asthma using unanesthetized, unrestrained animals. To measure airway function, ovalbumin (IgE)-sensitized animals are

  13. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  14. Microsurgical tunica albuginea transplantation in an animal model

    Directory of Open Access Journals (Sweden)

    Salvatore Sansalone

    2017-01-01

    Full Text Available Several andrological diseases require surgical repair or reconstruction of tunica albuginea, which envelops the corpora cavernosa penis. Despite intense research efforts involving a variety of biological materials, such as skin, muscle aponeurosis, human dura mater, tunica vaginalis, and pericardium, engineered tunica albuginea suitable for graft use is yet to be obtained. The study investigates microsurgical tunica albuginea allotransplantation in an animal model with the purpose of creation of an organ-specific tissue bank to store penile tissue, from cadaveric donors and male-to-female trans-sexual surgery, for allogeneic transplantation. Materials were tunica albuginea tissue explanted from 15 donor rats, cryopreserved at −80°C, gamma-irradiated, and implanted in 15 recipient rats, of which three rats were used as controls. Penile grafts were explanted at different time intervals; after macroscopic evaluation of the organ, the grafts were processed to morphological, histochemical, and immunohistochemical examinations by light microscopy. Detection of pro-inflammatory cytokines was also performed. Examination of the tunica albuginea allografts collected 1, 3, or 6 months after surgery and of control tunica albuginea fragments showed that tunica albuginea implants achieved biointegration with adjacent tissue at all-time points. The integration of cryopreserved rat tunica albuginea allografts, documented by our study, encourages the exploration of tunica albuginea allotransplantation in humans. In conclusion, the effectiveness and reliability of the tunica albuginea conditioning protocol described here suggest the feasibility of setting up a tunica albuginea bank as a further tissue bank.

  15. Environmental enrichment facilitates cocaine abstinence in an animal conflict model.

    Science.gov (United States)

    Ewing, Scott; Ranaldi, Robert

    2018-03-01

    In this study, we sought to discover if housing in an enriched environment (EE) is an efficacious intervention for encouraging abstinence from cocaine seeking in an animal "conflict" model of abstinence. Sixteen Long-Evans rats were trained in 3-h daily sessions to self-administer a cocaine solution (1 mg/kg/infusion) until each demonstrated a stable pattern of drug-seeking. Afterward, half were placed in EE cages equipped with toys, obstacles, and a running wheel, while the other half were given clean, standard laboratory housing. All rats then completed daily 30-min sessions during which the 2/3 of flooring closest to the self-administration levers was electrified, causing discomfort should they approach the levers; current strength (mA) was increased after every day of drug seeking until the rat ceased activity on the active lever for 3 consecutive sessions (abstinence). Rats housed in EE abstained after fewer days and at lower current strengths than rats in standard housing. These results support the idea that EE administered after the development of a cocaine-taking habit may be an effective strategy to facilitate abstinence. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. System identification of perilymphatic fistula in an animal model

    Science.gov (United States)

    Wall, C. 3rd; Casselbrant, M. L.

    1992-01-01

    An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans.

  17. Detection of bias in animal model pedigree indices of heifers

    Directory of Open Access Journals (Sweden)

    M. LIDAUER

    2008-12-01

    Full Text Available The objective of the study was to test whether the pedigree indices (PI of heifers are biased, and if so, whether the magnitude of the bias varies in different groups of heifers. Therefore, two animal model evaluations with two different data sets were computed. Data with all the records from the national evaluation in December 1994 was used to obtain estimated breeding values (EBV for 305-days' milk yield and protein yield. In the second evaluation, the PIs were estimated for cows calving the first time in 1993 by excluding all their production records from the data. Three different statistics, a simple t-test, the linear regression of EBV on PI, and the polynomial regression of the difference in the predictions (EBV-PI on PI, were computed for three groups of first parity Ayrshire cows: daughters of proven sires, daughters of young sires, and daughters of bull dam candidates. A practically relevant bias was found only in the PIs for the daughters of young sires. On average their PIs were biased upwards by 0.20 standard deviations (78.8 kg for the milk yield and by 0.21 standard deviations (2.2 kg for the protein yield. The polynomial regression analysis showed that the magnitude of the bias in the PIs changed somewhat with the size of the PIs.;

  18. Solitary mammals provide an animal model for autism spectrum disorders.

    Science.gov (United States)

    Reser, Jared Edward

    2014-02-01

    Species of solitary mammals are known to exhibit specialized, neurological adaptations that prepare them to focus working memory on food procurement and survival rather than on social interaction. Solitary and nonmonogamous mammals, which do not form strong social bonds, have been documented to exhibit behaviors and biomarkers that are similar to endophenotypes in autism. Both individuals on the autism spectrum and certain solitary mammals have been reported to be low on measures of affiliative need, bodily expressiveness, bonding and attachment, direct and shared gazing, emotional engagement, conspecific recognition, partner preference, separation distress, and social approach behavior. Solitary mammals also exhibit certain biomarkers that are characteristic of autism, including diminished oxytocin and vasopressin signaling, dysregulation of the endogenous opioid system, increased Hypothalamic-pituitary-adrenal axis (HPA) activity to social encounters, and reduced HPA activity to separation and isolation. The extent of these similarities suggests that solitary mammals may offer a useful model of autism spectrum disorders and an opportunity for investigating genetic and epigenetic etiological factors. If the brain in autism can be shown to exhibit distinct homologous or homoplastic similarities to the brains of solitary animals, it will reveal that they may be central to the phenotype and should be targeted for further investigation. Research of the neurological, cellular, and molecular basis of these specializations in other mammals may provide insight for behavioral analysis, communication intervention, and psychopharmacology for autism.

  19. Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

    Directory of Open Access Journals (Sweden)

    M. Di Domenico

    2012-01-01

    Full Text Available Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

  20. Dysbaric osteonecrosis in divers and caisson workers. An animal model.

    Science.gov (United States)

    Lehner, C E; Adams, W M; Dubielzig, R R; Palta, M; Lanphier, E H

    1997-11-01

    Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.

  1. Animal model for schizophrenia that reflects gene-environment interactions.

    Science.gov (United States)

    Nagai, Taku; Ibi, Daisuke; Yamada, Kiyofumi

    2011-01-01

    Schizophrenia is a devastating psychiatric disorder that impairs mental and social functioning and affects approximately 1% of the population worldwide. Genetic susceptibility factors for schizophrenia have recently been reported, some of which are known to play a role in neurodevelopment; these include neuregulin-1, dysbindin, and disrupted-in-schizophrenia 1 (DISC1). Moreover, epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. The possible interaction between environment and genetic susceptibility factors, especially during neurodevelopment, is proposed as a promising disease etiology of schizophrenia. Polyriboinosinic-polyribocytidilic acid (polyI : C) is a synthetic analogue of double-stranded RNA that leads to the pronounced but time-limited production of pro-inflammatory cytokines. Maternal immune activation by polyI : C exposure in rodents is known to precipitate a wide spectrum of behavioral, cognitive, and pharmacological abnormalities in adult offspring. Recently, we have reported that neonatal injection of polyI : C in mice results in schizophrenia-like behavioral alterations in adulthood. In this review, we show how gene-environment interactions during neurodevelopment result in phenotypic changes in adulthood by injecting polyI : C into transgenic mice that express a dominant-negative form of human DISC1 (DN-DISC1). Our findings suggest that polyI : C-treated DN-DISC1 mice are a well-validated animal model for schizophrenia that reflects gene-environment interactions.

  2. Food Addiction and Binge Eating: Lessons Learned from Animal Models

    Science.gov (United States)

    Diéguez, Carlos

    2018-01-01

    The feeding process is required for basic life, influenced by environment cues and tightly regulated according to demands of the internal milieu by regulatory brain circuits. Although eating behaviour cannot be considered “addictive” under normal circumstances, people can become “addicted” to this behaviour, similarly to how some people are addicted to drugs. The symptoms, cravings and causes of “eating addiction” are remarkably similar to those experienced by drug addicts, and both drug-seeking behaviour as eating addiction share the same neural pathways. However, while the drug addiction process has been highly characterised, eating addiction is a nascent field. In fact, there is still a great controversy over the concept of “food addiction”. This review aims to summarize the most relevant animal models of “eating addictive behaviour”, emphasising binge eating disorder, that could help us to understand the neurobiological mechanisms hidden under this behaviour, and to improve the psychotherapy and pharmacological treatment in patients suffering from these pathologies. PMID:29324652

  3. Implant healing in experimental animal models of diabetes.

    Science.gov (United States)

    Le, Nga N; Rose, Michael B; Levinson, Howard; Klitzman, Bruce

    2011-05-01

    influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices. © 2011 Diabetes Technology Society.

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

    Directory of Open Access Journals (Sweden)

    Schneider Erich

    2007-08-01

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

  5. An animal model of differential genetic risk for methamphetamine intake

    Directory of Open Access Journals (Sweden)

    Tamara ePhillips

    2015-09-01

    Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1 agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the

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

    Science.gov (United States)

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

    2018-06-01

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

  7. Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

    NARCIS (Netherlands)

    Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

    2017-01-01

    BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone

  8. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

    Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-01-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

  9. Disc volume reduction with percutaneous nucleoplasty in an animal model.

    Directory of Open Access Journals (Sweden)

    Richard Kasch

    Full Text Available STUDY DESIGN: We assessed volume following nucleoplasty disc decompression in lower lumbar spines from cadaveric pigs using 7.1Tesla magnetic resonance imaging (MRI. PURPOSE: To investigate coblation-induced volume reductions as a possible mechanism underlying nucleoplasty. METHODS: We assessed volume following nucleoplastic disc decompression in pig spines using 7.1-Tesla MRI. Volumetry was performed in lumbar discs of 21 postmortem pigs. A preoperative image data set was obtained, volume was determined, and either disc decompression or placebo therapy was performed in a randomized manner. Group 1 (nucleoplasty group was treated according to the usual nucleoplasty protocol with coblation current applied to 6 channels for 10 seconds each in an application field of 360°; in group 2 (placebo group the same procedure was performed but without coblation current. After the procedure, a second data set was generated and volumes calculated and matched with the preoperative measurements in a blinded manner. To analyze the effectiveness of nucleoplasty, volumes between treatment and placebo groups were compared. RESULTS: The average preoperative nucleus volume was 0.994 ml (SD: 0.298 ml. In the nucleoplasty group (n = 21 volume was reduced by an average of 0.087 ml (SD: 0.110 ml or 7.14%. In the placebo group (n = 21 volume was increased by an average of 0.075 ml (SD: 0.075 ml or 8.94%. The average nucleoplasty-induced volume reduction was 0.162 ml (SD: 0.124 ml or 16.08%. Volume reduction in lumbar discs was significant in favor of the nucleoplasty group (p<0.0001. CONCLUSIONS: Our study demonstrates that nucleoplasty has a volume-reducing effect on the lumbar nucleus pulposus in an animal model. Furthermore, we show the volume reduction to be a coblation effect of nucleoplasty in porcine discs.

  10. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

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

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-07-01

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

  12. Purkinje Cell Signaling Deficits in Animal Models of Ataxia

    Directory of Open Access Journals (Sweden)

    Eriola Hoxha

    2018-04-01

    Full Text Available Purkinje cell (PC dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction. Mutations affecting Na+ channels (NaV1.1, NaV1.6, NaVβ4, Fgf14 or Rer1 reduce the firing rate of PCs, mainly via an impairment of the Na+ resurgent current. Mutations that reduce Kv3 currents limit the firing rate frequency range. Mutations of Kv1 channels act mainly on inhibitory interneurons, generating excessive GABAergic signaling onto PCs, resulting in episodic ataxia. Kv4.3 mutations are responsible for a complex syndrome with several neurologic dysfunctions including ataxia. Mutations of either Cav or BK channels have similar consequences, consisting in a disruption of the firing pattern of PCs, with loss of precision, leading to ataxia. Another category of pathogenic mechanisms of ataxia regards alterations of synaptic signals arriving at the PC. At the parallel fiber (PF-PC synapse, mutations of glutamate delta-2 (GluD2 or its ligand Crbl1 are responsible for the loss of synaptic contacts, abolishment of long-term depression (LTD and motor deficits. At the same synapse, a correct function of metabotropic glutamate receptor 1 (mGlu1 receptors is necessary to avoid ataxia. Failure of climbing fiber (CF maturation and establishment of PC mono-innervation occurs in a great number of mutant mice, including mGlu1 and its transduction pathway, GluD2, semaphorins and their receptors. All these models have in common the alteration of PC output signals, due to a variety of mechanisms affecting incoming

  13. A Mathematical Model of Repeated Impregnation of Porous Bodies with Solutions of Polymers

    Directory of Open Access Journals (Sweden)

    I. V. Glebov

    2015-01-01

    not meet requirements.The paper presents a developed mathematical model of repeated impregnation of silica fabrics by bakelite varnish with intermediate drying of the workpiece. Equations determining the amount of the polymer and the volatile products after each impregnation-drying cycle are derived.Results of calculations obtained by the mathematical model are given. The calculation results show that the multiple impregnations allow us to increase the polymer content in the prepreg and provide required parameters for a few cycles of impregnation. In the calculations were also considered various drying options with removal of different amounts of solvent. The calculations have shown that providing the specified parameters is possible if more than 50% of solvent contained in the prepreg after impregnation is removed.The mathematical model is part of a patented vacuum manufacturing technology of prepregs and allows us to define the parameters of the prepreg according to the content of the polymer and the volatile products at each stage of the multiple impregnation process of the porous material.

  14. Impact of number of repeated scans on model observer performance for a low-contrast detection task in computed tomography.

    Science.gov (United States)

    Ma, Chi; Yu, Lifeng; Chen, Baiyu; Favazza, Christopher; Leng, Shuai; McCollough, Cynthia

    2016-04-01

    Channelized Hotelling observer (CHO) models have been shown to correlate well with human observers for several phantom-based detection/classification tasks in clinical computed tomography (CT). A large number of repeated scans were used to achieve an accurate estimate of the model's template. The purpose of this study is to investigate how the experimental and CHO model parameters affect the minimum required number of repeated scans. A phantom containing 21 low-contrast objects was scanned on a 128-slice CT scanner at three dose levels. Each scan was repeated 100 times. For each experimental configuration, the low-contrast detectability, quantified as the area under receiver operating characteristic curve, [Formula: see text], was calculated using a previously validated CHO with randomly selected subsets of scans, ranging from 10 to 100. Using [Formula: see text] from the 100 scans as the reference, the accuracy from a smaller number of scans was determined. Our results demonstrated that the minimum number of repeated scans increased when the radiation dose level decreased, object size and contrast level decreased, and the number of channels increased. As a general trend, it increased as the low-contrast detectability decreased. This study provides a basis for the experimental design of task-based image quality assessment in clinical CT using CHO.

  15. Intra-rater repeatability of the Oxford foot model in healthy children in different stages of the foot roll over process during gait

    DEFF Research Database (Denmark)

    Curtis, D J; Bencke, J; Stebbins, J A

    2009-01-01

    BACKGROUND: The repeatability of the Oxford foot model has been reported, but possible variations in the repeatability during the foot roll over process have not been examined. The aim of this study was to determine the relative and absolute repeatability of the model for each stage of the foot...... roll over process during gait and to compare foot kinematic data from this study with that from another centre as a preliminary examination of the model's inter-centre repeatability and validity. METHOD: Eight healthy children were tested twice at the gait laboratory. Foot kinematics from this study...... were plotted against those from an earlier repeatability study and repeatability statistics calculated for the three rockers of stance phase and swing phase. RESULTS: Foot kinematics from this study and an earlier repeatability study produced similar kinematic patterns and joint angle ranges...

  16. Identification of proteins in hyperglycemia and stroke animal models.

    Science.gov (United States)

    Sung, Jin-Hee; Shah, Fawad-Ali; Gim, Sang-Ah; Koh, Phil-Ok

    2016-01-01

    Stroke is a major cause of disability and death in adults. Diabetes mellitus is a metabolic disorder that strongly increases the risk of severe vascular diseases. This study compared changes in proteins of the cerebral cortex during ischemic brain injury between nondiabetic and diabetic animals. Adult male rats were injected with streptozotocin (40 mg/kg) via the intraperitoneal route to induce diabetes and underwent surgical middle cerebral artery occlusion (MCAO) 4 wk after streptozotocin treatment. Cerebral cortex tissues were collected 24 h after MCAO and cerebral cortex proteins were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Several proteins were identified as differentially expressed between nondiabetic and diabetic animals. Among the identified proteins, we focused on the following metabolism-related enzymes: isocitrate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, adenosylhomocysteinase, pyruvate kinase, and glucose-6-phosphate isomerase (neuroleukin). Expression of these proteins was decreased in animals that underwent MCAO. Moreover, protein expression was reduced to a greater extent in diabetic animals than in nondiabetic animals. Reverse transcription-polymerase chain reaction analysis confirmed that the diabetic condition exacerbates the decrease in expression of metabolism-related proteins after MCAO. These results suggest that the diabetic condition may exacerbate brain damage during focal cerebral ischemia through the downregulation of metabolism-related proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

    OpenAIRE

    Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

    2017-01-01

    BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, inter...

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

    Directory of Open Access Journals (Sweden)

    Aya Nakae

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    Wancket, L M

    2015-09-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  4. The impact of the postnatal gut microbiota on animal models

    DEFF Research Database (Denmark)

    Hansen, Axel Jacob Kornerup; Ejsing-Duun, Maria; Aasted, Bent

    2007-01-01

    Quality control of laboratory animals has been mostly concentrated on eliminating and securing the absence of specific infections, but event barrier bred laboratory animals harbour a huge number of gut bacteria. There is scientific evidence that the nature of the gut microbiota especially in early...... correlated to factors related to early exposure to microorganisms, e.g. the so-called hygiene hypothesis claims that the increasing human incidence of allergy. T1D, RA and IBD may be due to the lack of such exposure. It is possible today by various molecular techniques to profile the gut microbiota...

  5. Developing Pre-Algebraic Thinking in Generalizing Repeating Pattern Using SOLO Model

    Science.gov (United States)

    Lian, Lim Hooi; Yew, Wun Thiam

    2011-01-01

    In this paper, researchers discussed the application of the generalization perspective in helping the primary school pupils to develop their pre-algebraic thinking in generalizing repeating pattern. There are two main stages of the generalization perspective had been adapted, namely investigating and generalizing the pattern. Since the Biggs and…

  6. Design and analysis of effects of triplet repeat oligonucleotides in cell models for myotonic dystrophy

    NARCIS (Netherlands)

    Gonzalez-Barriga, A.; Mulders, S.A.M.; Giessen, J. van der; Hooijer, J.D.; Bijl, S.; Kessel, I.D.G. van; Beers, J. van; Deutekom, J.C. van; Fransen, J.A.M.; Wieringa, B.; Wansink, D.G.

    2013-01-01

    Myotonic dystrophy type 1 (DM1) is caused by DM protein kinase (DMPK) transcripts containing an expanded (CUG)n repeat. Antisense oligonucleotide (AON)-mediated suppression of these mutant RNAs is considered a promising therapeutic strategy for this severe disorder. Earlier, we identified a

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

    Science.gov (United States)

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

    2018-01-01

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

  8. Low-dose computed tomography to detect body-packing in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Maurer, M.H., E-mail: martin.maurer@charite.de [Klinik fuer Strahlenheilkunde, Charite - Universitaetsmedizin, Berlin (Germany); Niehues, S.M.; Schnapauff, D.; Grieser, C.; Rothe, J.H. [Klinik fuer Strahlenheilkunde, Charite - Universitaetsmedizin, Berlin (Germany); Waldmueller, D. [Bildungs- und Wissenschaftszentrum der Bundesfinanzverwaltung, Berlin (Germany); Chopra, S.S. [Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Charite - Universitaetsmedizin, Berlin (Germany); Hamm, B.; Denecke, T. [Klinik fuer Strahlenheilkunde, Charite - Universitaetsmedizin, Berlin (Germany)

    2011-05-15

    Objective: To assess the possible extent of dose reduction for low-dose computed tomography (CT) in the detection of body-packing (ingested drug packets) as an alternative to plain radiographs in an animal model. Materials and methods: Twelve packets containing cocaine (purity >80%) were introduced into the intestine of an experimental animal (crossbred pig), which was then repeatedly examined by abdominal CT with stepwise dose reduction (tube voltage, 80 kV; tube current, 10-350 mA). Three blinded readers independently evaluated the CT datasets starting with the lowest tube current and noted the numbers of packets detected at the different tube currents used. In addition, 1 experienced reader determined the number of packets detectable on plain abdominal radiographs and ultrasound. Results: The threshold for correct identification of all 12 drug packets was 100 mA for reader 1 and 125 mA for readers 2 and 3. Above these thresholds all 3 readers consistently identified all 12 packets. The effective dose of a low-dose CT scan with 125 mA (including scout view) was 1.0 mSv, which was below that of 2 conventional abdominal radiographs (1.2 mSv). The reader interpreting the conventional radiographs identified a total of 9 drug packets and detected 8 packets by abdominal ultrasound. Conclusions: Extensive dose reduction makes low-dose CT a valuable alternative imaging modality for the examination of suspected body-packers and might replace conventional abdominal radiographs as the first-line imaging modality.

  9. Repeated subretinal surgery and removal of subretinal decalin is well tolerated - evidence from a porcine model.

    Science.gov (United States)

    Sørensen, Nina Buus; Klemp, Kristian; Kjær, Troels Wesenberg; Heegaard, Steffen; la Cour, Morten; Kiilgaard, Jens Folke

    2017-09-01

    Subretinal perfluorocarbon liquid (PFCL) is a serious complication that can occur after retinal detachment repair. It is possible to remove the PFCL surgically, but retinal damage related to the procedure is unknown. Also, increasing interest in subretinal treatment makes it relevant to examine the functional and morphological consequences of repeated subretinal manipulation. We hypothesized that PFCL in a porcine model can be injected in the subretinal space and removed with minimal effect on retinal structure and function. The left eyes of ten healthy three-month-old female domestic pigs were included. Multifocal electroretinograms (mfERG) were recorded before surgery. Following vitrectomy, a PFCL bleb (decalin) was injected subretinally using a 41G cannula. After 14 days the decalin was removed through a 41G cannula in combination with a 2 ml syringe and an intermediate flexible tube. Two weeks after removal, a control mfERG was recorded, the pigs were enucleated and sacrificed and eyes were examined histologically. All statistics were carried out with a paired t-test in SAS Enterprise Guide 7.1® (SAS Institute Inc., Cary, NC, USA). There was no significant difference in mfERG amplitude ratio (left/right eye) between baseline and recordings two weeks after removal of decalin (P1 (M = 0.26, SD = 0.80, p = 0.39), second order kernel (M = -0.18, SD = 0.86, p = 0.57), Direct Response (M = 0.39, SD = 0.61, p = 0.12) or Induced Component (M = -0.03, SD = 0.40, p = 0.80)). Histologically, the photoreceptor outer segments were minimally affected. Otherwise the retina was normal 14 days after removal of decalin. In four pigs the subretinal decalin displaced inferiorly and was no longer accessible for removal. Subretinal decalin can be removed within 14 days without lasting retinal damage. Decalin is a heavy liquid where the risk of displacement is high. Future studies using PFCLs to control duration of an experimental retinal separation

  10. Studying the Mammalian Intestinal Microbiome Using Animal Models

    NARCIS (Netherlands)

    Hugenholtz, F.; Zhang, J.; O'Toole, P.W.; Smidt, H.

    2016-01-01

    The gastrointestinal (GI) tract of humans and animals is colonized by microorganisms immediately after birth. The composition of the GI tract microbiota undergoes remarkable alterations during early age, reaches a relative stable status in adulthood, and is driven by external factors such as

  11. Testing Experimental Compounds against Leishmaniansis in Laboratory Animal Model Systems

    Science.gov (United States)

    1984-09-01

    consulted in five human and two canine cases of suspected leishmaniasis. Two of the 5 human cases were isoenzyme typed as L. b. braziliensis ( Peru ...animal. The latter may be of use in controlling some of the complications of diabetes . %’Wr WF ’ 56 PU BLICAT I ONS_ Griffith, O.W., "Mechanism of

  12. Are animal models useful for studying human disc disorders / degeneration?

    NARCIS (Netherlands)

    Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

    2008-01-01

    Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

  13. Zebrafish: A Versatile Animal Model for Fertility Research

    Directory of Open Access Journals (Sweden)

    Jing Ying Hoo

    2016-01-01

    Full Text Available The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.

  14. Animal models : Implications for human aggression and violence

    NARCIS (Netherlands)

    de Boer, Sietse; Bushman, Brad

    2017-01-01

    A large body of animal neurobehavioral research convincingly demonstrates that abnormal expressions of aggressive behavior principally find their origin in a dys- regulation of the deeply rooted neuronal circuits and/or neurochemical pathways in the brain that mediate normal social

  15. Feedlot cattle susceptibility to heat stress: an animal specific model

    Science.gov (United States)

    The extreme effects of heat stress in a feedlot situation can cause losses exceeding 5% of all the cattle on feed in a single feedlot. These losses can be very devastating to a localized area of feedlot producers. Animal stress is a result of the combination of three different components: environm...

  16. Animal Models for Testing the DOHaD Hypothesis

    Science.gov (United States)

    Since the seminal work in human populations by David Barker and colleagues, several species of animals have been used in the laboratory to test the Developmental Origins of Health and Disease (DOHaD) hypothesis. Rats, mice, guinea pigs, sheep, pigs and non-human primates have bee...

  17. Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type.

    Science.gov (United States)

    Crestani, Carlos C

    2016-01-01

    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress.

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

    Science.gov (United States)

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

    2012-12-01

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

  19. Comparison of Repeated Measurement Design and Mixed Models in Evaluation of the Entonox Effect on Labor Pain

    Directory of Open Access Journals (Sweden)

    Nasim Karimi

    2017-01-01

    Full Text Available Background & objectives: In many medical studies, the response variable is measured repeatedly over time to evaluate the treatment effect that is known as longitudinal study. The analysis method for this type of data is repeated measures ANOVA that uses only one correlation structure and the results are not valid with inappropriate correlation structure. To avoid this problem, a convenient alternative is mixed models. So, the aim of this study was to compare of mixed and repeated measurement models for examination of the Entonox effect on the labor pain. Methods: This experimental study was designed to compare the effect of Entonox and oxygen inhalation on pain relief between two groups. Data were analyzed using repeated measurement and mixed models with different correlation structures. Selection and comparison of proper correlation structures performed using Akaike information criterion, Bayesian information criterion and restricted log-likelihood. Data were analyzed using SPSS-22. Results: Results of our study showed that all variables containing analgesia methods, labor duration of the first and second stages, and time were significant in these tests. In mixed model, heterogeneous first-order autoregressive, first-order autoregressive, heterogeneous Toeplitz and unstructured correlation structures were recognized as the best structures. Also, all variables were significant in these structures. Unstructured variance covariance matrix was recognized as the worst structure and labor duration of the first and second stages was not significant in this structure. Conclusions: This study showed that the Entonox inhalation has a significant effect on pain relief in primiparous and it is confirmed by all of the models.

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

    Science.gov (United States)

    Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

    2015-12-01

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

  1. Economic Crises and the Complexity of Animal Spirits Modeling

    Directory of Open Access Journals (Sweden)

    Grigore PIROŞCĂ

    2011-02-01

    Full Text Available The rationale of this research goes into the origins of the economic crises from a different way of economic thinking, hence the professional interest on bringing again into the light the concept of animal spirits, used for the first time from classic liberals like David Hume, developed by doctrine founder John Maynard Keynes, and captured as groundbreaking economic crisis hypothesis in Nobel Prize laureates’ books like George Akerlof. A familiar account of the last financial crisis underlines the collapse of confidence and evaporation of trust which leaded to failure of corporate governance and easy money policy. Nor were these problems of recent origin; they were rooted in deep structural changes in the economy that date back many years. Financial innovations overheated the world economy and gained steam because of irrational exuberance over a risk free better future. Considering the evidence analyzed in this paper work, this approach of economic crisis through animal spirits puts forward new highlights of economic thought.

  2. Pathogenicity of Cryptosporidium parvum - evaluation of an animal infection model

    DEFF Research Database (Denmark)

    Enemark, Heidi L.; Bille-Hansen, Vivi; Lind, Peter

    2003-01-01

    and rectum. The unintended presence of rotavirus in some of the experimental animals revealed an additive or synergistic effect between rotavirus and C. parvum as indicated by prolonged diarrhoea, increased oocyst shedding, decreased weight gain and elevated levels of serum haptoglobin and serum amyloid...... A (SAA) in piglets infected simultaneously with both pathogens. The difference in daily weight gain between infected and control animals was significant only for piglets co-infected with rotavirus. The acute phase response of haptoglobin and SAA was characterised by a large individual variation....... In piglets, co-infected with rotavirus, the levels of serum haptoglobin were 3.5 and 4.6 times higher in the infected versus the controls 6 and 9 dpi, respectively (mean values: 2411 mug/ml +/- S.D. 2023 and 1840 mug/ml +/- S.D. 1697). In the controls infected with rotavirus, peak haptoglobin concentration...

  3. A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pyburn, Tasia M.; Bensing, Barbara A.; Xiong, Yan Q.; Melancon, Bruce J.; Tomasiak, Thomas M.; Ward, Nicholas J.; Yankovskaya, Victoria; Oliver, Kevin M.; Cecchini, Gary; Sulikowski, Gary A.; Tyska, Matthew J.; Sullam, Paul M.; Iverson, T.M. (VA); (UCLA); (Vanderbilt); (UCSF)

    2014-10-02

    GspB is a serine-rich repeat (SRR) adhesin of Streptococcus gordonii that mediates binding of this organism to human platelets via its interaction with sialyl-T antigen on the receptor GPIb{alpha}. This interaction appears to be a major virulence determinant in the pathogenesis of infective endocarditis. To address the mechanism by which GspB recognizes its carbohydrate ligand, we determined the high-resolution x-ray crystal structure of the GspB binding region (GspB{sub BR}), both alone and in complex with a disaccharide precursor to sialyl-T antigen. Analysis of the GspB{sub BR} structure revealed that it is comprised of three independently folded subdomains or modules: (1) an Ig-fold resembling a CnaA domain from prokaryotic pathogens; (2) a second Ig-fold resembling the binding region of mammalian Siglecs; (3) a subdomain of unique fold. The disaccharide was found to bind in a pocket within the Siglec subdomain, but at a site distinct from that observed in mammalian Siglecs. Confirming the biological relevance of this binding pocket, we produced three isogenic variants of S. gordonii, each containing a single point mutation of a residue lining this binding pocket. These variants have reduced binding to carbohydrates of GPIb{alpha}. Further examination of purified GspB{sub BR}-R484E showed reduced binding to sialyl-T antigen while S. gordonii harboring this mutation did not efficiently bind platelets and showed a significant reduction in virulence, as measured by an animal model of endocarditis. Analysis of other SRR proteins revealed that the predicted binding regions of these adhesins also had a modular organization, with those known to bind carbohydrate receptors having modules homologous to the Siglec and Unique subdomains of GspBBR. This suggests that the binding specificity of the SRR family of adhesins is determined by the type and organization of discrete modules within the binding domains, which may affect the tropism of organisms for different tissues.

  4. Brachytherapy on restenosis. {sup 32}P radioisotope in animal model

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R.; Rivera, E.; Cocca, C.; Martin, G.; Cricco, G. [Buenos Aires Univ. (Argentina). School of Pharmacy and Biochemistry; Croci, M.; Guzman, L.

    2000-05-01

    Despite a notorious decline in age-adjusted death rates for cardiovascular pathologies, coronary artery disease still remains as the main cause of mortality above the age of 40 in men and 60 in women. More than 25% of death in persons over the age of 35 are due to coronary disease. In about 50% of men and 30% of women, the first manifestation of the disease is an acute myocardial infarction and 10% a sudden cardiac death. In Argentina it is estimated that in 1998 about 100.000-115.000 people suffered as first manifestation of coronary illness a myocardial acute infarct. Angioplasty has an important and well established site in the treatment of the coronary illness and restenosis represents the principal complication of this method for myocardial re-vascularization. About a 35-40% of treated arteries present restenosis within the first six month the intervention with the concomitant need of re-interventions, re-hospitalizations, by-pass surgery, work discontinuity and the high cost for the health system. A number of drugs were tested as anti-restenosis: anticoagulants, aspirin, antispasmodics and lipid-lowering agents but none was clearly efficient; also, experimental studies in which intravascular irradiation with different source types and energies, radiation doses and doses rate to prevent restenosis was utilized; however, there is no consensus in many aspects of this intravascular brachytherapy. The first step in this work was to induce the experimental model in rabbits. Afterwards, by means of the balloon methodology and stent implantation, brachytherapy experiments were carried out to evaluate the biological effect on different layers of arteries, with different Doses using a beta particle emitting radioisotope ({sup 32}P). The arteriosclerotic lesions were induced in New Zealand rabbits through the administration of a diet with high cholesterol content. Angioplastic interventions on femoral arteries were done with balloon methodology and controlled by

  5. Brachytherapy on restenosis. 32P radioisotope in animal model

    International Nuclear Information System (INIS)

    Bergoc, R.; Rivera, E.; Cocca, C.; Martin, G.; Cricco, G.; Croci, M.; Guzman, L.

    2000-01-01

    Despite a notorious decline in age-adjusted death rates for cardiovascular pathologies, coronary artery disease still remains as the main cause of mortality above the age of 40 in men and 60 in women. More than 25% of death in persons over the age of 35 are due to coronary disease. In about 50% of men and 30% of women, the first manifestation of the disease is an acute myocardial infarction and 10% a sudden cardiac death. In Argentina it is estimated that in 1998 about 100.000-115.000 people suffered as first manifestation of coronary illness a myocardial acute infarct. Angioplasty has an important and well established site in the treatment of the coronary illness and restenosis represents the principal complication of this method for myocardial re-vascularization. About a 35-40% of treated arteries present restenosis within the first six month the intervention with the concomitant need of re-interventions, re-hospitalizations, by-pass surgery, work discontinuity and the high cost for the health system. A number of drugs were tested as anti-restenosis: anticoagulants, aspirin, antispasmodics and lipid-lowering agents but none was clearly efficient; also, experimental studies in which intravascular irradiation with different source types and energies, radiation doses and doses rate to prevent restenosis was utilized; however, there is no consensus in many aspects of this intravascular brachytherapy. The first step in this work was to induce the experimental model in rabbits. Afterwards, by means of the balloon methodology and stent implantation, brachytherapy experiments were carried out to evaluate the biological effect on different layers of arteries, with different Doses using a beta particle emitting radioisotope ( 32 P). The arteriosclerotic lesions were induced in New Zealand rabbits through the administration of a diet with high cholesterol content. Angioplastic interventions on femoral arteries were done with balloon methodology and controlled by fluoroscopy

  6. Repeated short climatic change affects the epidermal differentiation program and leads to matrix remodeling in a human organotypic skin model.

    Science.gov (United States)

    Boutrand, Laetitia-Barbollat; Thépot, Amélie; Muther, Charlotte; Boher, Aurélie; Robic, Julie; Guéré, Christelle; Vié, Katell; Damour, Odile; Lamartine, Jérôme

    2017-01-01

    Human skin is subject to frequent changes in ambient temperature and humidity and needs to cope with these environmental modifications. To decipher the molecular response of human skin to repeated climatic change, a versatile model of skin equivalent subject to "hot-wet" (40°C, 80% relative humidity [RH]) or "cold-dry" (10°C, 40% RH) climatic stress repeated daily was used. To obtain an exhaustive view of the molecular mechanisms elicited by climatic change, large-scale gene expression DNA microarray analysis was performed and modulated function was determined by bioinformatic annotation. This analysis revealed several functions, including epidermal differentiation and extracellular matrix, impacted by repeated variations in climatic conditions. Some of these molecular changes were confirmed by histological examination and protein expression. Both treatments (hot-wet and cold-dry) reduced the expression of genes encoding collagens, laminin, and proteoglycans, suggesting a profound remodeling of the extracellular matrix. Strong induction of the entire family of late cornified envelope genes after cold-dry exposure, confirmed at protein level, was also observed. These changes correlated with an increase in epidermal differentiation markers such as corneodesmosin and a thickening of the stratum corneum, indicating possible implementation of defense mechanisms against dehydration. This study for the first time reveals the complex pattern of molecular response allowing adaption of human skin to repeated change in its climatic environment.

  7. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    International Nuclear Information System (INIS)

    Inoue, Yusuke; Okubo, Toshiyuki; Tojo, Arinobu; Sekine, Rieko; Soda, Yasushi; Kobayashi, Seiichiro; Nomura, Akiko; Izawa, Kiyoko; Kitamura, Toshio; Ohtomo, Kuni

    2006-01-01

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  8. A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

    Directory of Open Access Journals (Sweden)

    Edward Rockenstein

    Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

  9. Production of Accurate Skeletal Models of Domestic Animals Using Three-Dimensional Scanning and Printing Technology

    Science.gov (United States)

    Li, Fangzheng; Liu, Chunying; Song, Xuexiong; Huan, Yanjun; Gao, Shansong; Jiang, Zhongling

    2018-01-01

    Access to adequate anatomical specimens can be an important aspect in learning the anatomy of domestic animals. In this study, the authors utilized a structured light scanner and fused deposition modeling (FDM) printer to produce highly accurate animal skeletal models. First, various components of the bovine skeleton, including the femur, the…

  10. Teaching Neurophysiology, Neuropharmacology, and Experimental Design Using Animal Models of Psychiatric and Neurological Disorders

    Science.gov (United States)

    Morsink, Maarten C.; Dukers, Danny F.

    2009-01-01

    Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…

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

    Science.gov (United States)

    2016-03-14

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

  12. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

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

    OpenAIRE

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

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

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

    Directory of Open Access Journals (Sweden)

    Armfield Jason M

    2007-12-01

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

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

    Science.gov (United States)

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

    2008-03-01

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

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

    Science.gov (United States)

    Andersen, Monica L; Winter, Lucile M F

    2017-09-04

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

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

    Science.gov (United States)

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

    2018-02-01

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

  18. Mice selected for high versus low stress reactivity: a new animal model for affective disorders.

    Science.gov (United States)

    Touma, Chadi; Bunck, Mirjam; Glasl, Lisa; Nussbaumer, Markus; Palme, Rupert; Stein, Hendrik; Wolferstätter, Michael; Zeh, Ramona; Zimbelmann, Marina; Holsboer, Florian; Landgraf, Rainer

    2008-07-01

    Affective disorders such as major depression are among the most prevalent and costly diseases of the central nervous system, but the underlying mechanisms are still poorly understood. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions (hyper- or hypo-activity) of the hypothalamic-pituitary-adrenal (HPA) axis, play a prominent role in the development of major depressive disorders. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel parameters underlying increased or decreased stress reactivity. Starting from a population of outbred mice (parental generation: 100 males and 100 females of the CD-1 strain), two breeding lines were established according to the outcome of a 'stress reactivity test' (SRT), consisting of a 15-min restraint period and tail blood samplings immediately before and after exposure to the stressor. Mice showing a very high or a very low secretion of corticosterone in the SRT, i.e. animals expressing a hyper- or a hypo-reactivity of the HPA axis, were selected for the 'high reactivity' (HR) and the 'low reactivity' (LR) breeding line, respectively. Additionally, a third breeding line was established consisting of animals with an 'intermediate reactivity' (IR) in the SRT. Already in the first generation, i.e. animals derived from breeding pairs selected from the parental generation, significant differences in the reactivity of the HPA axis between HR, IR, and LR mice were observed. Moreover, these differences were found across all subsequent generations and could be increased by selective breeding, which indicates a genetic basis of the respective phenotype. Repeated testing of individuals in the SRT furthermore proved that the observed differences in stress responsiveness are present already early in life and can be regarded as a robust genetic predisposition. Tests investigating the animal's emotionality including anxiety

  19. Experimental and modelling buckling of wood-based columns under repeated loading

    Directory of Open Access Journals (Sweden)

    Nafa Z.

    2010-06-01

    Full Text Available Collapse of timber constructions can appear under the effect of load that exceeds the resistance of a carrying element or under the effect of a geometrical instability like buckling. In addition, loading can be constant or varying for example loads due to wind or earthquakes. The aim of this paper is to study the behaviour and the lifetime of columns in wood or based-wood material such as glulam (GL or laminated veneer lumber (LVL under repeated loading leading to buckling.

  20. Identification of Pentatricopeptide Repeat Proteins in the Model Organism Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Sam Manna

    2013-01-01

    Full Text Available Pentatricopeptide repeat (PPR proteins are RNA binding proteins with functions in organelle RNA metabolism. They are found in all eukaryotes but have been most extensively studied in plants. We report on the identification of 12 PPR-encoding genes in the genome of the protist Dictyostelium discoideum, with potential homologs in other members of the same lineage and some predicted novel functions for the encoded gene products in protists. For one of the gene products, we show that it localizes to the mitochondria, and we also demonstrate that antisense inhibition of its expression leads to slower growth, a phenotype associated with mitochondrial dysfunction.

  1. How to study sex differences in addiction using animal models.

    Science.gov (United States)

    Carroll, Marilyn E; Lynch, Wendy J

    2016-09-01

    The importance of studying sex as a biological variable in biomedical research is becoming increasingly apparent. There is a particular need in preclinical studies of addiction to include both sexes, as female animals are often excluded from studies, leaving large gaps in our knowledge of not only sex differences and potential prevention and treatment strategies but also with regard to the basic neurobiology of addiction. This review focuses on methodology that has been developed in preclinical studies to examine sex differences in the behavioral aspects and neurobiological mechanisms related to addiction across the full range of the addiction process, including initiation (acquisition), maintenance, escalation, withdrawal, relapse to drug seeking and treatment. This review also discusses strategic and technical issues that need to be considered when comparing females and males, including the role of ovarian hormones and how sex differences interact with other major vulnerability factors in addiction, such as impulsivity, compulsivity and age (adolescent versus adult). Novel treatments for addiction are also discussed, such as competing non-drug rewards, repurposed medications such as progesterone and treatment combinations. Practical aspects of conducting research comparing female and male animals are also considered. Making sex differences a point of examination requires additional effort and consideration; however, such studies are necessary given mounting evidence demonstrating that the addiction process occurs differently in males and females. These studies should lead to a better understanding of individual differences in the development of addiction and effective treatments for males and females. © 2016 Society for the Study of Addiction.

  2. Prediction and repeatability of milk coagulation properties and curd-firming modeling parameters of ovine milk using Fourier-transform infrared spectroscopy and Bayesian models.

    Science.gov (United States)

    Ferragina, A; Cipolat-Gotet, C; Cecchinato, A; Pazzola, M; Dettori, M L; Vacca, G M; Bittante, G

    2017-05-01

    The aim of this study was to apply Bayesian models to the Fourier-transform infrared spectroscopy spectra of individual sheep milk samples to derive calibration equations to predict traditional and modeled milk coagulation properties (MCP), and to assess the repeatability of MCP measures and their predictions. Data consisted of 1,002 individual milk samples collected from Sarda ewes reared in 22 farms in the region of Sardinia (Italy) for which MCP and modeled curd-firming parameters were available. Two milk samples were taken from 87 ewes and analyzed with the aim of estimating repeatability, whereas a single sample was taken from the other 915 ewes. Therefore, a total of 1,089 analyses were performed. For each sample, 2 spectra in the infrared region 5,011 to 925 cm -1 were available and averaged before data analysis. BayesB models were used to calibrate equations for each of the traits. Prediction accuracy was estimated for each trait and model using 20 replicates of a training-testing validation procedure. The repeatability of MCP measures and their predictions were also compared. The correlations between measured and predicted traits, in the external validation, were always higher than 0.5 (0.88 for rennet coagulation time). We confirmed that the most important element for finding the prediction accuracy is the repeatability of the gold standard analyses used for building calibration equations. Repeatability measures of the predicted traits were generally high (≥95%), even for those traits with moderate analytical repeatability. Our results show that Bayesian models applied to Fourier-transform infrared spectra are powerful tools for cheap and rapid prediction of important traits in ovine milk and, compared with other methods, could help in the interpretation of results. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. Social Fear Learning: from Animal Models to Human Function.

    Science.gov (United States)

    Debiec, Jacek; Olsson, Andreas

    2017-07-01

    Learning about potential threats is critical for survival. Learned fear responses are acquired either through direct experiences or indirectly through social transmission. Social fear learning (SFL), also known as vicarious fear learning, is a paradigm successfully used for studying the transmission of threat information between individuals. Animal and human studies have begun to elucidate the behavioral, neural and molecular mechanisms of SFL. Recent research suggests that social learning mechanisms underlie a wide range of adaptive and maladaptive phenomena, from supporting flexible avoidance in dynamic environments to intergenerational transmission of trauma and anxiety disorders. This review discusses recent advances in SFL studies and their implications for basic, social and clinical sciences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV.

    Directory of Open Access Journals (Sweden)

    Margaret R Lentz

    Full Text Available There are currently no widely accepted neuro-HIV small animal models. We wanted to validate the HIV-1 Transgenic rat (Tg as an appropriate neuro-HIV model and then establish in vivo imaging biomarkers of neuropathology, within this model, using MR structural and diffusion tensor imaging (DTI.Young and middle-aged Tg and control rats were imaged using MRI. A subset of middle-aged animals underwent longitudinal repeat imaging six months later. Total brain volume (TBV, ventricular volume (VV and parenchymal volume (PV = TBV-VV were measured. Fractional anisotropy (FA and mean diffusivity (MD values of the corpus callosum (CC were calculated from DTI data.TBV and PV were smaller in Tg compared to control rats in young and middle-aged cohorts (p0.05.We detected brain volume loss in the Tg rat, probably due to astrocytic dysfunction/loss, loss of structural/axonal matrix and striatal neuronal loss as suggested by immunofluorescence. Increased MD and decreased FA in the CC probably reflect microstructural differences between the Tg and Control rats which could include increased extracellular space between white matter tracts, demyelination and axonal degeneration, among other pathologies. We believe that the Tg rat is an adequate model of neuropathology in HIV and that volumetric MR and DTI measures can be potentially used as biomarkers of disease progression.

  6. Characterizing Cognitive Aging in Humans with Links to Animal Models

    Directory of Open Access Journals (Sweden)

    Gene E Alexander

    2012-09-01

    Full Text Available With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline.

  7. Biosafety assessment of transgenic Bt cotton on model animals

    Directory of Open Access Journals (Sweden)

    Sadia Bano

    2016-05-01

    Full Text Available Abstract Background: To know the effects of transgenic crops on soil microorganisms, animals and other expected hazards due to the introduction of GM crops into the environment is critical both scientifically and environmentally. The work was conducted to study the effect of insecticidal Bt protein on Rats and Earthworms. Methods: For this purpose, animals like rat and soil organisms like Earthworm were selected. Rats were selected on the basis of