WorldWideScience

Sample records for animal model study

  1. 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.

  2. 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.

  3. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    develop fulminant hepatitis, acute hepatitis, or chronic liver disease after adoptive transfer, and others spontaneously develop hepatocellular carcinoma (HCC. Among HCV transgenic mice, most develop no disease, but acute hepatitis has been observed in one model, and HCC in another. Although mice are not susceptible to HBV and HCV, their ability to replicate these viruses and to develop liver diseases characteristic of human infections provides opportunities to study pathogenesis and develop novel therapeutics In the search for the mechanism of hepatocarcinogenesis in hepatitis viral infection, two viral proteins, the core protein of hepatitis C virus (HCV and the HBx protein of hepatitis B virus (HBV, have been shown to possess oncogenic potential through transgenic mouse studies, indicating the direct involvement of the hepatitis viruses in hepatocarcinogenesis.

    This may explain the very high frequency of HCC in patients with HCV or HBV infection.

    Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV. Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees.

    Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate

  4. Animal models to study plaque vulnerability

    NARCIS (Netherlands)

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

    2007-01-01

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

  5. Animal models

    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...

  6. 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.

  7. 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...

  8. Animal models.

    Science.gov (United States)

    Walker, Ellen A

    2010-01-01

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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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?...

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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 ...

  3. 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.

  4. 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

  5. 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

  6. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    OpenAIRE

    Loria-Cervera, Elsy Nalleli; Andrade-Narvaez, Fernando Jose

    2014-01-01

    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 tis...

  7. Animal Models of Hemophilia

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nabeela Nathoo

    2014-01-01

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

  9. Cytogenetical evaluation of a new animal model for radiobiological studies

    International Nuclear Information System (INIS)

    Nasazzi, N.; Taja, M.R.; Nagle, C.; Gimenez, J.C.

    1992-01-01

    The response of a New World monkey species (Cebus apella paraguayanus) lymphocytes to various doses of 60 Co gamma-rays has been studied using dicentrics + rings frequency in first mitosis and compared to that of man. Results have shown that differences between both species are no significant. The distribution of 200 breakpoints in G-banded metaphases has been scored showing an excess of breaks in chromosomes 1, 11, 12 and 16. Terminal heterochromatin blocks differ from intercalar heterochromatin in the response to gamma radiation being the former more affected. (author)

  10. Cytogenetical evaluation of a new animal model for radiobiological studies

    Energy Technology Data Exchange (ETDEWEB)

    Nasazzi, N.; Taja, M.R. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Nagle, C. [Centro de Educacion Medica e Investigaciones Clinicas, Buenos Aires (Argentina); Gimenez, J.C. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina)

    1992-07-01

    The response of a New World monkey species (Cebus apella paraguayanus) lymphocytes to various doses of 60 Co gamma-rays has been studied using dicentrics + rings frequency in first mitosis and compared to that of man. Results have shown that differences between both species are no significant. The distribution of 200 breakpoints in G-banded metaphases has been scored showing an excess of breaks in chromosomes 1, 11, 12 and 16. Terminal heterochromatin blocks differ from intercalar heterochromatin in the response to gamma radiation being the former more affected. (author)

  11. Therapeutic study of proton beam in vascular disease animal models

    International Nuclear Information System (INIS)

    Lee, Y. M.; Jang, K. H.; Kim, M. J.; Choi, J. H.

    2010-04-01

    We previously reported that proton beam inhibited angiogenic vessels in zebrafish and that proton induced cancer cell apoptosis via p53 induction as well as caspase-3 activity. In this study, we performed to identity the effect of candidate chemicals on the angiogenic inhibition in vitro and in vivo (zebrafish Flk1:EGFP transgenic fish). And we treated small cell lung adenocarcinoma cell line, A549 cells with proton beam in combination with angiogenic inhibitors we found in this study. By the MTT assay, we performed cell viability assay with cancer cells and we investigated that HIF-1α induction by proton beam by the western blot analysis. We found novel anti-angiogenic chemicals from traditional herb. That is decursin, and glyceollins from the Angelica gigas, and soy bean. Decrusin and glyceollins inhibited VEGF- or bFGF-induced endothelial cell proliferation, migration and zebrafish microvessel development. Moreover, glyceollins inhibited hypoxia-induced HIF-1α in a dose dependent manner. However, proton beam itself did not induce HIF-1α whereas it increased HIF-1α stability under hypoxia. Even proton beam induced cell death of A549 small cell lung carcinoma cells but the combination of decrusin or glyceollins did not increase the cancer cell death

  12. Therapeutic study of proton beam in vascular disease animal models

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. M.; Jang, K. H.; Kim, M. J.; Choi, J. H. [Kyungpook National University, Daegu (Korea, Republic of)

    2010-04-15

    We previously reported that proton beam inhibited angiogenic vessels in zebrafish and that proton induced cancer cell apoptosis via p53 induction as well as caspase-3 activity. In this study, we performed to identity the effect of candidate chemicals on the angiogenic inhibition in vitro and in vivo (zebrafish Flk1:EGFP transgenic fish). And we treated small cell lung adenocarcinoma cell line, A549 cells with proton beam in combination with angiogenic inhibitors we found in this study. By the MTT assay, we performed cell viability assay with cancer cells and we investigated that HIF-1{alpha} induction by proton beam by the western blot analysis. We found novel anti-angiogenic chemicals from traditional herb. That is decursin, and glyceollins from the Angelica gigas, and soy bean. Decrusin and glyceollins inhibited VEGF- or bFGF-induced endothelial cell proliferation, migration and zebrafish microvessel development. Moreover, glyceollins inhibited hypoxia-induced HIF-1{alpha} in a dose dependent manner. However, proton beam itself did not induce HIF-1{alpha} whereas it increased HIF-1{alpha} stability under hypoxia. Even proton beam induced cell death of A549 small cell lung carcinoma cells but the combination of decrusin or glyceollins did not increase the cancer cell death

  13. Modelling Farm Animal Welfare

    Science.gov (United States)

    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

  15. The guinea pig as an animal model for developmental and reproductive toxicology studies.

    Science.gov (United States)

    Rocca, Meredith S; Wehner, Nancy G

    2009-04-01

    Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

  16. 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.

  17. Use of animal models for space flight physiology studies, with special focus on the immune system

    Science.gov (United States)

    Sonnenfeld, Gerald

    2005-01-01

    Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

  18. Modelling Farm Animal Welfare

    Directory of Open Access Journals (Sweden)

    Chérie E. Part

    2013-05-01

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

  19. Animal models of tinnitus.

    Science.gov (United States)

    Brozoski, Thomas J; Bauer, Carol A

    2016-08-01

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

  20. Animal models of sarcoidosis.

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Endometriosis research: animal models for the study of a complex disease.

    Science.gov (United States)

    Tirado-González, Irene; Barrientos, Gabriela; Tariverdian, Nadja; Arck, Petra C; García, Mariana G; Klapp, Burghard F; Blois, Sandra M

    2010-11-01

    Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Animal Models in Sexual Medicine: The Need and Importance of Studying Sexual Motivation.

    Science.gov (United States)

    Ventura-Aquino, Elisa; Paredes, Raúl G

    2017-01-01

    Many different animal models of sexual medicine have been developed, demonstrating the complexity of studying the many interactions that influence sexual responses. A great deal of effort has been invested in measuring sexual motivation using different behavioral models mainly because human behavior is more complex than any model can reproduce. To compare different animal models of male and female behaviors that measure sexual motivation as a key element in sexual medicine and focus on models that use a combination of molecular techniques and behavioral measurements. We review the literature to describe models that evaluate different aspects of sexual motivation. No single test is sufficient to evaluate sexual motivation. The best approach is to evaluate animals in different behavioral tests to measure the motivational state of the subject. Different motivated behaviors such as aggression, singing in the case of birds, and sexual behavior, which are crucial for reproduction, are associated with changes in mRNA levels of different receptors in brain areas that are important in the control of reproduction. Research in animal models is crucial to understand the complexity of sexual behavior and all the mechanisms that influence such an important aspect of human well-being to decrease the physiologic and psychological impact of sexual dysfunctions. In other cases, research in different models is necessary to understand and recognize, not cure, the variability of sexuality, such as asexuality, which is another form of sexual orientation. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  4. Using human brain imaging studies as a guide towards animal models of schizophrenia

    Science.gov (United States)

    BOLKAN, Scott S.; DE CARVALHO, Fernanda D.; KELLENDONK, Christoph

    2015-01-01

    Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients. PMID:26037801

  5. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

    Directory of Open Access Journals (Sweden)

    Chang RB

    2015-04-01

    Full Text Available Renbao Chang,1 Xudong Liu,1 Shihua Li,2 Xiao-Jiang Li1,2 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Abstract: Huntington’s disease (HD is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. Keywords: transgenic animal models, Huntington’s disease, pathogenesis, therapy

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  8. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  9. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. A new small-animal model for the study of acquired heterotopic ossification after hip surgery.

    Science.gov (United States)

    Anthonissen, Joris; Ossendorf, Christian; Hock, Johanna Lisa; Ritz, Ulrike; Hofmann, Alexander; Rommens, Pol Maria

    2015-01-01

    Heterotopic ossification (HO)--the formation of bone in soft tissues--is a frequent problem after surgery of the hip and pelvis, but little is known about its underlying pathogenic mechanisms. It is vital to study the underlying pathogenesis in animal models to develop and evaluate new prophylactic regimens directed against HO. However, previously developed small-animal models for the study of HO imitate neither surgery nor trauma-mechanisms that potentially cause HO. Hence, the goal of this study was to develop a novel small-animal model imitating hip surgery that can reliably produce HO. Twenty male Wistar rats were subjected to surgery of the right hip during which the femoral canal was reamed in three steps up to 2 mm, and a muscle lesion was made. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography. Eighteen of 20 animals showed HO around the hip 12 weeks after surgery. The amount of heterotopic bone varied from very small particles up to near ankylosis. A rat model of hip/pelvic surgery that does not use exogenous osteogenic stimulus and can reliably produce HO was developed.

  12. Animal models of cerebral ischemia

    Science.gov (United States)

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

    2015-11-01

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

  13. Animal models for the study of hepatitis C virus infection and related liver disease

    DEFF Research Database (Denmark)

    Bukh, Jens

    2012-01-01

    Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important...... for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T......- and B- cell deficient mice with human chimeric livers. Although these mice cannot be used in studies of adaptive immunity, they have provided new insights into HCV neutralization, interactions between virus and receptors, innate host responses, and therapeutic approaches. Recent progress in developing...

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

    Directory of Open Access Journals (Sweden)

    Carole Fureix

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

  15. [Drosophila melanogaster as a model for studying the function of animal viral proteins].

    Science.gov (United States)

    Omelianchuk, L V; Iudina, O S

    2011-07-01

    Studies in which Drosophila melanogaster individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell are much less host-specific. Due to this, the model of Drosophila with its developed system of searching for genetic interactions can be used to find intracellular targets for the action of viral proteins of the second group.

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

    Science.gov (United States)

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

    2018-02-01

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

  17. Towards an Ethological Animal Model of Depression? A Study on Horses

    Science.gov (United States)

    Fureix, Carole; Jego, Patrick; Henry, Séverine; Lansade, Léa; Hausberger, Martine

    2012-01-01

    Background Recent reviews question current animal models of depression and emphasise the need for ethological models of mood disorders based on animals living under natural conditions. Domestic horses encounter chronic stress, including potential stress at work, which can induce behavioural disorders (e.g. “apathy”). Our pioneering study evaluated the potential of domestic horses in their usual environment to become an ethological model of depression by testing this models’ face validity (i.e. behavioural similarity with descriptions of human depressive states). Methodology/Principal Findings We observed the spontaneous behaviour of 59 working horses in their home environment, focusing on immobility bouts of apparent unresponsiveness when horses displayed an atypical posture (termed withdrawn hereafter), evaluated their responsiveness to their environment and their anxiety levels, and analysed cortisol levels. Twenty-four percent of the horses presented the withdrawn posture, also characterized by gaze, head and ears fixity, a profile that suggests a spontaneous expression of “behavioural despair”. When compared with control “non-withdrawn” horses from the same stable, withdrawn horses appeared more indifferent to environmental stimuli in their home environment but reacted more emotionally in more challenging situations. They exhibited lower plasma cortisol levels. Withdrawn horses all belonged to the same breed and females were over-represented. Conclusions/Significance Horse might be a useful potential candidate for an animal model of depression. Face validity of this model appeared good, and potential genetic input and high prevalence of these disorders in females add to the convergence. At a time when current animal models of depression are questioned and the need for novel models is expressed, this study suggests that novel models and biomarkers could emerge from ethological approaches in home environments. PMID:22761752

  18. Animal Models in Burn Research

    Science.gov (United States)

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

    2014-01-01

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

  19. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    Science.gov (United States)

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Animating climate model data

    Science.gov (United States)

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

    2006-05-01

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

  1. A study Antiurolithiatic Activity of ethanolic extract of Asparagus racemosus in animal models

    Directory of Open Access Journals (Sweden)

    Jagannath N

    2015-12-01

    Full Text Available Objective: To investigate the Antiurolithiatic Activity of ethanolic extract of Asparagus racemosus in animal models.Materials and Methods: The study includes performing on healthy albino rats of either sex weighing 220 – 270gms and urolithiasis was induced by oral administration of ethylene glycol and ammonium chloride water. The parameters studied are serum analysis for Urea, Creatinine, Calcium and Phosphorus, Body Weight of animals included in the study group and Histopathological Study of kidney for the presences crystals.  Results In our study the Ethanolic extract of Asparagus Racemosus with doses of 800mg/kg and 1600mg/kg per orally to rats showed significant reduction in serum urea, creatinine, calcium and phosphorus levels in urolithiatic rats when compared to the positive control rats (Group II. These results were found to be statistically significant (p<0.05.Conclusion: Ethanol Extract of Asparagus racemosus has a significant antiurolithiatic activity.

  2. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    Directory of Open Access Journals (Sweden)

    Joseph W. Golden

    2015-01-01

    Full Text Available Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.

  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. Cariogenicity Of Different Types Of Milk: An Experimental Study Using Animal Model.

    OpenAIRE

    Peres R.C.; Coppi L.C.; Franco E.M.; Volpato M.C.; Groppo F.C.; Rosalen P.L.

    2002-01-01

    This study evaluated the cariogenic potential of infant formulas and cow's milk, using a high cariogenic challenge in the animal model. Sixty female Wistar rats infected with Streptococcus sobrinus and desalivated were randomly divided into 6 groups, which received ad libitum: 1) sterilized deionized distilled water (SDW) with 5% sucrose; 2) cow's milk; 3) Nan 2; 4) Nestogeno 2; 5) Ninho growth supporting; 6) SDW. Groups 1 and 6 also received essential diet NCP#2 by gavage, twice a day. After...

  5. An Exploratory Study on the Development of an Animal Model of Acute Pancreatitis Following Nicotine Exposure

    Directory of Open Access Journals (Sweden)

    Chowdhury P

    2003-09-01

    Full Text Available Abstract Cigarette smoking is known to be a major risk factor for pancreatic cancer and pancreatitis is believed to be a predisposed condition for pancreatic cancer. As of this date, there is no established experimental animal model to conduct detailed studies on these two deadly diseases. Our aim is to establish a rodent model by which we can systematically study the pathogenesis of pancreatitis and pancreatic cancer. Methods Adult Male Sprague Dawley rats were exposed to graded doses of nicotine by various routes for periods of three to 16 weeks. Blood samples were measured for hormonal and metabolic parameters. The pancreas was evaluated for histopathological changes and its function was assessed in isolated pancreatic acini upon stimulation with cholecystokinin (CCK or carbachol (Cch. The pancreatic tissue was evaluated further for oncogene expression. Results Body weight, food and fluid intakes, plasma glucose and insulin levels were significantly reduced in animals with nicotine exposure when compared to control. However, CCK and gastrin levels in the blood were significantly elevated. Pancreatic function was decreased significantly with no alteration in CCK receptor binding. Pancreatic histology revealed vacuolation, swelling, cellular pyknosis and karyorrhexis. Mutant oncogene, H-ras, was overexpressed in nicotine-treated pancreatic tissue. Summary and conclusion The results suggest that alterations in metabolic, hormonal and pathologic parameters following nicotine-treatment appear consistent with diagnostic criteria of human pancreatitis. It is proposed that rats could be considered as a potential animal model to study the pathogenesis of pancreatitis.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Otitis media with effusion in an allergic animal model: A functional and morphological study.

    Science.gov (United States)

    Kim, Dong-Kee; Park, Hyu Eun; Back, Sang-A; Park, Hyang Rim; Kim, Soo Whan; Park, Yooyeon; Yeo, Sang Won; Park, Shi-Nae

    2016-05-01

    Allergy is considered as one of important etiologic factor of otitis media with effusion (OME). In present study, we evaluated the causal effect of allergy on OME in an animal model, and investigated the secondary effect of bacterial infection. Allergy and control animals were subdivided into groups with and without intratympanic injection of lipopolysaccharide (IT-LPS). Allergic otitis media was induced via intraperitoneal ovo-albumin injection with intranasal challenge. We assessed the occurrence of OME in allergic animals and the effect of IT-LPS on allergic otitis media. We also investigated the Th1 and Th2 responses in the middle-ear mucosa. Hearing of the animals was measured by ABR and DPOAE. OME was observed in 75% of the allergic animals. After IT-LPS, 100% of the control and allergy groups showed otitis media. Light microscopy revealed that the middle-ear mucosa of animals of both groups also was significantly increased after IT-LPS, and the Th1 response (IL-2 and IFN-γ) and Th2 response (IL-5 and IL-13) cytokines were expressed at higher levels in the allergy group with IT-LPS than in control group with IT-LPS. Hearing tests between the allergy and control group with IT-LPS did not reveal any differences. Our findings may be direct evidence of an allergic causal effect on OME. Th2 response cytokines were strongly expressed in allergic OME, and the inflammatory reaction to LPS was more intense in the allergic group, which indicates that otitis media related to allergy can be severely aggravated by an inflammatory reaction to bacterial infection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

    Science.gov (United States)

    Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

    2018-02-15

    Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

  9. A novel nasal powder formulation of glucagon: toxicology studies in animal models

    OpenAIRE

    Reno, Frederick E.; Normand, Patrick; McInally, Kevin; Silo, Sherwin; Stotland, Patricia; Triest, Myriam; Carballo, Dolores; Pich?, Claude

    2015-01-01

    Background Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10?% w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. Methods The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2?mg of GNP/day (0.1 and 0.2?mg glucagon/rat/day). The second study evaluated 28-da...

  10. Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review.

    Science.gov (United States)

    García, Y; Díaz-Castro, J

    2013-10-01

    Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion-repletion of hemoglobin is a method commonly used in animal studies. Three depletion-repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs.

  11. 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.

  12. Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

    Science.gov (United States)

    Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

    2013-01-01

    Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

  13. Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits.

    Science.gov (United States)

    de Cesar Netto, Cesar; Godoy-Santos, Alexandre Leme; Augusto Pontin, Pedro; Natalino, Renato Jose Mendonça; Pereira, Cesar Augusto Martins; Lima, Francisco Diego de Oliveira; da Fonseca, Lucas Furtado; Staggers, Jackson Rucker; Cavinatto, Leonardo Muntada; Schon, Lew Charles; de Camargo, Olavo Pires; Fernandes, Túlio Diniz

    2018-01-01

    Our goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8±2,28) and HD group (5,6±2,51), when compared to controls (2±0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.

  14. Experimental studies in the bronchial circulation. Which is the ideal animal model?

    Science.gov (United States)

    Panagiotou, Ioannis; Tsipas, Panteleimon; Melachrinou, Maria; Alexopoulos, Dimitrios; Dougenis, Dimitrios

    2014-01-01

    Background The importance of the role of bronchial arteries is notable in modern days thoracic surgery. The significance of their anastomoses with adjusted structures has not yet been sufficiently rated, especially in cases of haemoptysis, heart-lung transplantations and treatment of aneurysms of the thoracic aorta. The need of a thorough study is more relevant than ever and appropriate laboratory animals are required. Methods We review the literature in order to highlight the ideal experimental animal for the implementation of pilot programs relative to the bronchial circulation. A comparative analysis of the anatomy of the bronchial arterial system in humans along with these of pigs, dogs, rats, and birds, as being the most commonly used laboratory animals, is presented in details. Results The pig has the advantage that the broncho-oesophageal artery usually originates from the aorta as a single vessel, which makes the recognition and dissection of the artery easy to perform. In dogs, there is significant anatomical variation of the origin of the bronchial arteries. In rats, bronchial artery coming from the aorta is a rare event while in birds the pattern of the bronchial artery tree is clearly different from the human analog. Conclusions The pig is anatomically and physiologically suited for experimental studies on the bronchial circulation. The suitable bronchial anatomy and physiology along with the undeniable usefulness of the pig in experimental research and the low maintenance cost make the pig the ideal model for experiments in bronchial circulation. PMID:25364530

  15. Convergent integration of animal model and human studies of bipolar disorder (manic-depressive illness).

    Science.gov (United States)

    Le-Niculescu, Helen; Patel, Sagar D; Niculescu, Alexander B

    2010-10-01

    Animal models and human studies of bipolar disorder and other psychiatric disorders are becoming increasingly integrated, prompted by recent successes. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit-to-disease way of extracting reproducible and biologically important signal, in sharp contrast to the fit-to-cohort effect, disappointing findings to date, and limited reproducibility of human genetic analyses alone. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer biology and diabetes. Copyright © 2010. Published by Elsevier Ltd.

  16. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    Directory of Open Access Journals (Sweden)

    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  17. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  18. Promoting Profit Model Innovation in Animation Project in Northeast Asia: Case Study on Chinese Cultural and Creative Industry

    OpenAIRE

    Hao Jiao; Yupei Wang; Hongjun Xiao; Jianghua Zhou; Wensi Zeng

    2017-01-01

    Building on a case study of three animation companies in the Chinese cultural and creative industry, this study aims to understand how profit model innovation is promoted. Due to the rapidly changing environments and resource scarcity, cultural and creative companies need to select the appropriate profit model according to their own key resources. The study uncovers two critical factors that promote profit model innovation in animation projects: the quantity of consumers and their consumption...

  19. 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

  20. Animal Models for Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Helieh S. Oz

    2011-01-01

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

  1. Animal Models for Periodontal Disease

    Science.gov (United States)

    Oz, Helieh S.; Puleo, David A.

    2011-01-01

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

  2. 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

  3. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  4. A novel animal model for in vivo study of liver cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Shinsuke Fujiwara; Katsutoshi Yoshizato; Hikaru Fujioka; Chise Tateno; Ken Taniguchi; Masahiro Ito; Hiroshi Ohishi; Rie Utoh; Hiromi Ishibashi; Takashi Kanematsu

    2012-01-01

    AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator (uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse line (uPA/SCID mice).Host mice were divided into two groups (A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index (RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A (RI =22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL (range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies (RI =12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of

  5. Using physical models to study the gliding performance of extinct animals.

    Science.gov (United States)

    Koehl, M A R; Evangelista, Dennis; Yang, Karen

    2011-12-01

    Aerodynamic studies using physical models of fossil organisms can provide quantitative information about how performance of defined activities, such as gliding, depends on specific morphological features. Such analyses allow us to rule out hypotheses about the function of extinct organisms that are not physically plausible and to determine if and how specific morphological features and postures affect performance. The purpose of this article is to provide a practical guide for the design of dynamically scaled physical models to study the gliding of extinct animals using examples from our research on the theropod dinosaur, †Microraptor gui, which had flight feathers on its hind limbs as well as on its forelimbs. Analysis of the aerodynamics of †M. gui can shed light on the design of gliders with large surfaces posterior to the center of mass and provide functional information to evolutionary biologists trying to unravel the origins of flight in the dinosaurian ancestors and sister groups to birds. Measurements of lift, drag, side force, and moments in pitch, roll, and yaw on models in a wind tunnel can be used to calculate indices of gliding and parachuting performance, aerodynamic static stability, and control effectiveness in maneuvering. These indices permit the aerodynamic performance of bodies of different shape, size, stiffness, texture, and posture to be compared and thus can provide insights about the design of gliders, both biological and man-made. Our measurements of maximum lift-to-drag ratios of 2.5-3.1 for physical models of †M. gui suggest that its gliding performance was similar to that of flying squirrels and that the various leg postures that might have been used by †M. gui make little difference to that aspect of aerodynamic performance. We found that body orientation relative to the movement of air past the animal determines whether it is difficult or easy to maneuver.

  6. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies.

    Science.gov (United States)

    Stuchlik, Ales; Radostová, Dominika; Hatalova, Hana; Vales, Karel; Nekovarova, Tereza; Koprivova, Jana; Svoboda, Jan; Horacek, Jiri

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1-3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD.

  7. 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.

  8. Animal models to study the impact of nutrition on the immune system of the transition cow.

    Science.gov (United States)

    Dänicke, Sven; Meyer, Ulrich; Kersten, Susanne; Frahm, Jana

    2018-02-01

    The immune system is particularly challenged in transition cows as marked physiological changes occur in this period which are driven by late gestation, partus and onset of lactation. As a consequence, the metabolic and nutritional state of the cow also changes significantly with possible implications for the plasticity and flexibility of the immune system. In order to understand how the balance between metabolism, nutritional status and the immune system is maintained under challenging conditions, such as an infection, various animal models can be used which specifically manipulate the nutritional status through various feeding and management strategies. Such models aim at exploring the immunological response to a challenge under largely varying nutritional and metabolic states. As energy balance (EB) is strongly associated both with the metabolic state and with the immunoreactivity of the cows the manipulation of the EB by either influencing energy intake or energy excretion with milk, or by both, offers model opportunities for studying EB effects on the immune system. For example, assigning cows with a higher body condition score (BCS) at least 6 weeks prior to calving to an energy-dense diet exceeding the energy requirement in combination with a decelerated increase in the concentrate feed proportion post partum was shown to be effective in inducing a ketotic metabolic state under ad libitum feeding conditions. Compared to an adequately managed control group this model allows studying immune responses in the transit period and in dependence on dietary interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Estradiol Valerate-induced Polycystic Ovary Syndrome: An Animal Model Study

    Directory of Open Access Journals (Sweden)

    F Mesbah

    2011-01-01

    Full Text Available Introduction & Objective: Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder and one of the most common causes of an ovulation among women in their reproductive age. Presence of cysts in the ovaries alteration in the blood levels of gonadotropine hormones and gaining weight are some of the main characteristics of PCOS among humans. Our goal was to investigate the possible occurrence of such conditions in animal models of PCOS. Materials & Methods: Forty five Sprague Dawely rats were divided into 3 equal groups: the treatment and sham groups were intramuscularly injected by a single dose of Estradiol Valerate (4 mg/rat, dissolved in 0.4 ml and equal volume of olive oil, respectively, and the control group without any injection. During the 12 weeks of study, the animal’s weights were measured once a week. After 8 weeks, serum levels of testosterone, estrogen, progesterone, Follicular Stimulating Hormone (FSH, Latinizing Hormone (LH and glucose were measured. Following 12 weeks, ovaries were removed and prepared for light microscopy. Histological characteristics of ovaries were observed after hematoxylin-eosin staining. Results: Animal weight and serum level of testosterone were significantly reduced among PCOS induced rats while progesterone, LH and glucose levels were elevated. There was no significant difference in estradiol and FSH levels among different group of animals. Many cysts and degenerating follicles were observed in the treatment group. Conclusion: PCOS can be experimentally produced by a single injection of Estradiol Valerate in the rat, but some of the complex aspects of PCOS are not clearly defined.

  10. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

    Directory of Open Access Journals (Sweden)

    Apurba Mukherjee

    2009-06-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  11. Fast synthesis of 11C-Raclopride and its initial PET study on animal model

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Yao Shulin; Ding Weimin; Yin Dayi; Liu Boli

    2008-01-01

    Objective: 11 C-Raclopride is a type-2 dopamine receptor (D 2 R) binding agent used in the study of Parkinson's disease. This study introduced a fast and convenient method for preparation of 11 C- Raclopride and reported on the preclinical trial of this receptor tracer on animal studies. Methods: 11 C- Raclopride was synthesized via reaction of 11 C-CH 3 -Triflate with Nor-Raclopride. The mixture of primary product was water-diluted and loaded on Sep-Pak C18 column for separation. The final product, 11 C-Raclopride, was purified by column chromatography and then eluted from the C18 column with ethanol. The bio-distribution was studied in SD rats and the in vivo imaging pattern was studied in hem ipark insonjan mon- keys. Results: Within 16 min from beginning of processing with 11 CO 2 , the synthetic yield of 11 C-Raclopride was 60%, radiochemical purity (RCP) > 95% and specific activity 8 GBq/mmol. The uptake ratios of striatum to cerebellum and cerebral cortex were 4.67 and 6.20, respectively, at 30 min after 11 C-Raclopride administration. The striatal uptake in normal rat brain could be blocked by N-methylspiperone (NMSP) and raclopride, but not by Nor-raclopride. PET imaging showed higher striatal D 2 R uptake on the D 2 receptor up-regulated side of the experimental monkeys relative to the contralateral side. Conclusions: Column chromatography for purification of 11 C-Raclopride was fast, convenient and with a RCP similar to that of high performance liquid chromatography purification. Preliminary PET findings using animal model suggested that 11 C-Raclopride by column chromatogram purification might be considered for clinical use. (authors)

  12. Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence.

    Science.gov (United States)

    Wang, Lin; Lin, Guiting; Lee, Yung-Chin; Reed-Maldonado, Amanda B; Sanford, Melissa T; Wang, Guifang; Li, Huixi; Banie, Lia; Xin, Zhengcheng; Lue, Tom F

    2017-02-01

    To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI). Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Lepr fa 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Lepr fa 185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition. The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  13. ANIMAL MODELS IN SURGICAL

    African Journals Online (AJOL)

    ASSEMBLED BY

    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 ...

  14. ANIMAL MODELS FOR IMMUNOTOXICITY

    Science.gov (United States)

    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...

  15. An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat.

    Science.gov (United States)

    Rahman, Nadeem U; Phonsombat, Surat; Bochinski, Derek; Carrion, Rafael E; Nunes, Lora; Lue, Tom F

    2007-09-01

    To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.

  16. 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...

  17. Pneumothorax monitoring by remittance measurement: Comparison between experimental model and animal studies

    NARCIS (Netherlands)

    Beek, J. F.; Menovsky, T.; van Straaten, H. L.; Sterenborg, H. J.; Koppe, J. G.; van Gemert, M. J.

    1999-01-01

    Pneumothorax monitoring by remittance measurement in neonatology is investigated using model experiments. The results are compared to previous animal experiments. A multifibre probe is used to measure the change in remittance at 632.8 nm and 790 nm as a function of the thickness of a layer of air

  18. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studie

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Radostová, Dominika; Hatalová, Hana; Valeš, Karel; Nekovářová, Tereza; Kopřivová, J.; Svoboda, Jan; Horáček, J.

    2016-01-01

    Roč. 10, Oct 26 (2016), č. článku 209. ISSN 1662-5153 R&D Projects: GA MZd(CZ) NV15-34524A Institutional support: RVO:67985823 Keywords : OCD * quinpirole * animal model * brain circuits * rat * human Subject RIV: FH - Neurology Impact factor: 3.104, year: 2016

  19. Genetics of Adiposity in Large Animal Models for Human Obesity-Studies on Pigs and Dogs.

    Science.gov (United States)

    Stachowiak, M; Szczerbal, I; Switonski, M

    2016-01-01

    The role of domestic mammals in the development of human biomedical sciences has been widely documented. Among these model species the pig and dog are of special importance. Both are useful for studies on the etiology of human obesity. Genome sequences of both species are known and advanced genetic tools [eg, microarray SNP for genome wide association studies (GWAS), next generation sequencing (NGS), etc.] are commonly used in such studies. In the domestic pig the accumulation of adipose tissue is an important trait, which influences meat quality and fattening efficiency. Numerous quantitative trait loci (QTLs) for pig fatness traits were identified, while gene polymorphisms associated with these traits were also described. The situation is different in dog population. Generally, excessive accumulation of adipose tissue is considered, similar to humans, as a complex disease. However, research on the genetic background of canine obesity is still in its infancy. Between-breed differences in terms of adipose tissue accumulation are well known in both animal species. In this review we show recent advances of studies on adipose tissue accumulation in pigs and dogs, and their potential importance for studies on human obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakagama

    2011-02-01

    Full Text Available Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropylamine (BOP into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5’ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  1. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    International Nuclear Information System (INIS)

    Takahashi, Mami; Hori, Mika; Mutoh, Michihiro; Wakabayashi, Keiji; Nakagama, Hitoshi

    2011-01-01

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention

  2. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Mami, E-mail: mtakahas@ncc.go.jp; Hori, Mika; Mutoh, Michihiro [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Wakabayashi, Keiji [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526 (Japan); Nakagama, Hitoshi [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  3. 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.

  4. 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.

  5. Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

    Science.gov (United States)

    2016-10-01

    dependent cancers. Thus, in collaboration with Concordia Pharmaceuticals Inc., FTS was developed into and oral drug, Salirasib®. The drug has been already...AIA) rat model − a classical animal model for RA − imply that FTS attenuates disease manifestation, as assessed by: clinical scores; MRI imaging...be used to assess joint inflammation/damage and the immune response, as follows: arthritis clinical scores; MRI scans, micro-CT; histopathology

  6. Apoptosis imaging studies in various animal models using radio-iodinated peptide.

    Science.gov (United States)

    Kwak, Wonjung; Ha, Yeong Su; Soni, Nisarg; Lee, Woonghee; Park, Se-Il; Ahn, Heesu; An, Gwang Il; Kim, In-San; Lee, Byung-Heon; Yoo, Jeongsoo

    2015-01-01

    Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40% decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200% increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

  7. Animal models for studying transport across the blood-brain barrier.

    Science.gov (United States)

    Bonate, P L

    1995-01-01

    There are many reasons for wishing to determine the rate of uptake of a drug from blood into brain parenchyma. However, when faced with doing so for the first time, choosing a method can be a formidable task. There are at least 7 methods from which to choose: indicator dilution, brain uptake index, microdialysis, external registration, PET scanning, in situ perfusion, and compartmental modeling. Each method has advantages and disadvantages. Some methods require very little equipment while others require equipment that can cost millions of dollars. Some methods require very little technical experience whereas others require complex surgical manipulation. The mathematics alone for the various methods range from simple algebra to complex integral calculus and differential equations. Like most things in science, as the complexity of the technique increases, so does the quantity of information it provides. This review is meant to serve as a starting point for the researcher who wishes to study transport and uptake across the blood-brain barrier in animal models. An overview of the mathematical theory, as well as an introduction to the techniques, is presented.

  8. Persistent influence of maternal obesity on offspring health: Mechanisms from animal models and clinical studies.

    Science.gov (United States)

    Wankhade, Umesh D; Thakali, Keshari M; Shankar, Kartik

    2016-11-05

    The consequences of excessive maternal weight and adiposity at conception for the offspring are now well recognized. Maternal obesity increases the risk of overweight and obesity even in children born with appropriate-for-gestational age (AGA) birth weights. Studies in animal models have employed both caloric excess and manipulation of macronutrients (especially high-fat) to mimic hypercaloric intake present in obesity. Findings from these studies show transmission of susceptibility to obesity, metabolic dysfunction, alterations in glucose homeostasis, hepatic steatosis, skeletal muscle metabolism and neuroendocrine changes in the offspring. This review summarizes the essential literature in this area in both experimental and clinical domains and focuses on the translatable aspects of these experimental studies. Moreover this review highlights emerging mechanisms broadly explaining maternal obesity-associated developmental programming. The roles of early developmental alterations and placental adaptations are also reviewed. Increasing evidence also points to changes in the epigenome and other emerging mechanisms such as alterations in the microbiome that may contribute to persistent changes in the offspring. Finally, we examine potential interventions that have been employed in clinical cohorts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. 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

  10. 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.

  11. Exploratory metabolomics study of the experimental opisthorchiasis in a laboratory animal model (golden hamster, Mesocricetus auratus.

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    Daria A Kokova

    2017-10-01

    Full Text Available Opisthorchiasis is a parasitic infection caused by the liver flukes of the Opisthorchiidae family. Both experimental and epidemiological data strongly support a role of these parasites in the etiology of the hepatobiliary pathologies and an increased risk of intrahepatic cholangiocarcinoma. Understanding a functional link between the infection and hepatobiliary pathologies requires a detailed description a host-parasite interaction on different levels of biological regulation including the metabolic response on the infection. The last one, however, remains practically undocumented. Here we are describing a host response on Opisthorchiidae infection using a metabolomics approach and present the first exploratory metabolomics study of an experimental model of O. felineus infection.We conducted a Nuclear Magnetic Resonance (NMR based longitudinal metabolomics study involving a cohort of 30 animals with two degrees of infection and a control group. An exploratory analysis shows that the most noticeable trend (30% of total variance in the data was related to the gender differences. Therefore further analysis was done of each gender group separately applying a multivariate extension of the ANOVA-ASCA (ANOVA simultaneous component analysis. We show that in the males the infection specific time trends are present in the main component (43.5% variance, while in the females it is presented only in the second component and covers 24% of the variance. We have selected and annotated 24 metabolites associated with the observed effects and provided a physiological interpretation of the findings.The first exploratory metabolomics study an experimental model of O. felineus infection is presented. Our data show that at early stage of infection a response of an organism unfolds in a gender specific manner. Also main physiological mechanisms affected appear rather nonspecific (a status of the metabolic stress the data provides a set of the hypothesis for a search

  12. Studying the Immunomodulatory Effects of Small Molecule Ras Inhibitors in Animal Models of Rheumatoid Arthritis

    Science.gov (United States)

    2016-10-01

    collaboration with Concordia Pharmaceuticals Inc., FTS was developed into and oral drug, Salirasib®. The drug has been already tested in the clinic for the...animal model for RA − imply that FTS attenuates disease manifestation, as assessed by: clinical scores; MRI imaging; histopathology; and serum levels...inflammation/damage and the immune response, as follows: arthritis clinical scores; MRI scans, micro-CT; histopathology examination by a blinded pathologist

  13. 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....

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

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    Fabio Panariello

    2011-01-01

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

  15. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

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    Heidi Mulcahy

    2011-10-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

  16. Developmental programming of metabolic diseases – a review of studies on experimental animal models

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    Iwona Piotrowska

    2014-06-01

    Full Text Available Growth and development in utero is a complex and dynamic process that requires interaction between the mother organism and the fetus. The delivery of macro – and micronutrients, oxygen and endocrine signals has crucial importance for providing a high level of proliferation, growth and differentiation of cells, and a disruption in food intake not only has an influence on the growth of the fetus, but also has negative consequences for the offspring’s health in the future. Diseases that traditionally are linked to inappropriate life style of adults, such as type 2 diabetes, obesity, and arterial hypertension, can be “programmed” in the early stage of life and the disturbed growth of the fetus leads to the symptoms of the metabolic syndrome. The structural changes of some organs, such as the brain, pancreas and kidney, modifications of the signaling and metabolic pathways in skeletal muscles and in fatty tissue, epigenetic mechanisms and mitochondrial dysfunction are the basis of the metabolic disruptions. The programming of the metabolic disturbances is connected with the disruption in the intrauterine environment experienced in the early and late gestation period. It causes the changes in deposition of triglycerides, activation of the hormonal “stress axis” and disturbances in the offspring’s glucose tolerance. The present review summarizes experimental results that led to the identification of the above-mentioned links and it underlines the role of animal models in the studies of this important concept.

  17. Promoting Profit Model Innovation in Animation Project in Northeast Asia: Case Study on Chinese Cultural and Creative Industry

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    Hao Jiao

    2017-12-01

    Full Text Available Building on a case study of three animation companies in the Chinese cultural and creative industry, this study aims to understand how profit model innovation is promoted. Due to the rapidly changing environments and resource scarcity, cultural and creative companies need to select the appropriate profit model according to their own key resources. The study uncovers two critical factors that promote profit model innovation in animation projects: the quantity of consumers and their consumption intention. According to these two dimensions, the authors’ analysis shows profit model innovation in animation projects can be divided into Fans mode, Popular mode, Placement mode, and Failure mode, respectively. This study provides an empirical basis for advocating profit model innovation and discusses the resource requirements of Fan mode, Popular model, and Placement mode in China’s cultural and creative industry. The authors’ research also has managerial implications that might help firms promote profit model innovation. Finally, learning and promoting the profit model of China’s animation industry in the Northeast Asia area will be conducive to Northeast Asia’s cooperation and sustainable development.

  18. 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

  19. The characteristics of mine explosion injury of wading in shoal: A study on an animal model

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    Sen ZHANG

    2017-11-01

    Full Text Available Objective To study the characteristics and mechanism of mine blast injury that wading in shoal of different depths through an animal model. Methods Ninety-six healthy adult New Zealand white rabbits weighing 2.19±0.12kg were randomly divided into land group (n=16, limb wading group (n=16, the water depth reaching up the middle of the thighs of rabbits, and chest wading group (n=16, the water depth reaching up the thoracic xiphoid, stress test group (n=30, fake injury group (n=18. Punctiform burster was used to simulate landmine. Electric ignited the simulated mine away, causing landmine explosion injury to rabbits' one-sided hind limbs in upright state. High-speed photography was used to observe the movement of water accompanying the simulated mine explosion. Arterial blood serum markers of myocardial injury (CK-MB, cTnI and nerve injury (MBP, NSE were detected before injury, and 3, 6 and 12h after injury, and echocardiography, electrocardiography, CT, DSA and other examinations were implemented at the same time. Survival animals were killed 12h after injury for anatomy to record their injuries to the limbs and distant organs. The histopathological examination was done to define the injury characteristics further. Results Feet and distal tibia were broken, and closed femoral fractures and arterial damage were often found away from the stump in limb wading group. This type of injury was different from the mop-like tearing tissue in the land group. Chest, abdominal organs and the brain, spinal cord injury in wading group were more severe than those in land group. There were higher incidences of chest, abdominal organs and spinal cord injury in chest wading Group. Conclusion The energy transfer of underwater explosion is affected by water depth and limbs or trunk mutually, which is an important mechanism of the complex and serious injuries in the wading group. The wading depth is an important factor affecting severity of the injury. Based on

  20. Review of animal models used to study effects of bee products on wound healing: findings and applications

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    Hananeh Wael M.

    2015-09-01

    Full Text Available Non-healing wounds are associated with high morbidity and might greatly impact a patient’s well-being and economic status. For many years, scientific research has focused on developing and testing several natural and synthetic materials that enhance the rate of wound healing or eliminate healing complications. Honey has been used for thousands of years as a traditional remedy for many ailments. Recently, honey has reemerged as a promising wound care product especially for infected wounds and for wounds in diabetic patients. In addition to its proposed potent broad-spectrum antibacterial properties, honey has been claimed to promote wound healing by reducing wound hyperaemia, oedema, and exudate, and by stimulating angiogenesis, granulation tissue formation and epithelialisation. Several animal models, including large animals, dogs and cats, and different species of laboratory animals have been used to investigate the efficacy and safety of various natural and synthetic agents for wound healing enhancement. Interpreting the results obtained by these studies is, however, rather difficult and usually hampered by many limiting factors including great variation in types and origins of honey, the type of animal species used as models, the type of wounds, the number of animals, the number and type of controls, and variation in treatment protocols. In this article, we provide a comprehensive review of the most recent findings and applications of published experimental and clinical trials using honey as an agent for wound healing enhancement in different animal models.

  1. Animal welfare and the refinement of neuroscience research methods--a case study of Huntington's disease models.

    Science.gov (United States)

    Olsson, I Anna S; Hansen, Axel K; Sandøe, Peter

    2008-07-01

    The use of animals in biomedical and other research presents an ethical dilemma: we do not want to lose scientific benefits, nor do we want to cause laboratory animals to suffer. Scientists often refer to the potential human benefits of animal models to justify their use. However, even if this is accepted, it still needs to be argued that the same benefits could not have been achieved with a mitigated impact on animal welfare. Reducing the adverse effects of scientific protocols ('refinement') is therefore crucial in animal-based research. It is especially important that researchers share knowledge on how to avoid causing unnecessary suffering. We have previously demonstrated that even in studies in which animal use leads to spontaneous death, scientists often fail to report measures to minimize animal distress (Olsson et al. 2007). In this paper, we present the full results of a case study examining reports, published in peer-reviewed journals between 2003 and 2004, of experiments employing animal models to study the neurodegenerative disorder Huntington's disease. In 51 references, experiments in which animals were expected to develop motor deficits so severe that they would have difficulty eating and drinking normally were conducted, yet only three references were made to housing adaptation to facilitate food and water intake. Experiments including end-stages of the disease were reported in 14 papers, yet of these only six referred to the euthanasia of moribund animals. If the reference in scientific publications reflects the actual application of refinement, researchers do not follow the 3Rs (replacement, reduction, refinement) principle. While in some cases, it is clear that less-than-optimal techniques were used, we recognize that scientists may apply refinement without referring to it; however, if they do not include such information in publications, it suggests they find it less relevant. Journal publishing policy could play an important role: first, in

  2. A comparison of the different animal models of Fetal Alcohol Spectrum Disorders and their use in studying complex behaviors.

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    Anna R Patten

    2014-09-01

    Full Text Available Prenatal ethanol exposure (PNEE has been linked to widespread impairments in brain structure and function. There are a number of animal models that are used to study the structural and functional deficits caused by prenatal ethanol exposure, including, but not limited to: invertebrates, fish, rodents and non-human primates. Animal models enable a researcher to control important variables such as the route of ethanol administration, as well as the timing, frequency and amount of ethanol exposure. Each animal model and system of exposure has its place, depending on the research question being undertaken. In this review we will examine the different routes of ethanol administration and the various animal models of FASD that are commonly used in research, emphasizing their strengths and limitations. We will also present an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on behavior across the lifespan, focusing on learning and memory, olfaction, social, executive and motor functions. Special emphasis will be placed where the various animal models best represent deficits observed in the human condition and offer a viable test bed to examine potential therapeutics for humans with FASD.

  3. Insight into the relationship between impulsivity and substance abuse from studies using animal models.

    Science.gov (United States)

    Winstanley, Catharine A; Olausson, Peter; Taylor, Jane R; Jentsch, J David

    2010-08-01

    Drug use disorders are often accompanied by deficits in the capacity to efficiently process reward-related information and to monitor, suppress, or override reward-controlled behavior when goals are in conflict with aversive or immediate outcomes. This emerging deficit in behavioral flexibility and impulse control may be a central component of the progression to addiction, as behavior becomes increasingly driven by drugs and drug-associated cues at the expense of more advantageous activities. Understanding how neural mechanisms implicated in impulse control are affected by addictive drugs may therefore prove a useful strategy in the search for new treatment options. Animal models of impulsivity and addiction could make a significant contribution to this endeavor. Here, some of the more common behavioral paradigms used to measure different aspects of impulsivity across species are outlined, and the importance of the response to reward-paired cues in such paradigms is discussed. Naturally occurring differences in forms of impulsivity have been found to be predictive of future drug self-administration, but drug exposure can also increase impulsive responding. Such data are in keeping with the suggestion that impulsivity may contribute to multiple stages within the spiral of addiction. From a neurobiological perspective, converging evidence from rat, monkey, and human studies suggest that compromised functioning within the orbitofrontal cortex may critically contribute to the cognitive sequelae of drug abuse. Changes in gene transcription and protein expression within this region may provide insight into the mechanism underlying drug-induced cortical hypofunction, reflecting new molecular targets for the treatment of uncontrolled drug-seeking and drug-taking behavior.

  4. An expanded One Health model: integrating social science and One Health to inform study of the human-animal interface.

    Science.gov (United States)

    Woldehanna, Sara; Zimicki, Susan

    2015-03-01

    Zoonotic disease emergence is not a purely biological process mediated only by ecologic factors; opportunities for transmission of zoonoses from animals to humans also depend on how people interact with animals. While exposure is conditioned by the type of animal and the location in which interactions occur, these in turn are influenced by human activity. The activities people engage in are determined by social as well as contextual factors including gender, age, socio-economic status, occupation, social norms, settlement patterns and livelihood systems, family and community dynamics, as well as national and global influences. This paper proposes an expanded "One Health" conceptual model for human-animal exposure that accounts for social as well as epidemiologic factors. The expanded model informed a new study approach to document the extent of human exposure to animals and explore the interplay of social and environmental factors that influence risk of transmission at the individual and community level. The approach includes a formative phase using qualitative and participatory methods, and a representative, random sample survey to quantify exposure to animals in a variety of settings. The paper discusses the different factors that were considered in developing the approach, including the range of animals asked about and the parameters of exposure that are included, as well as factors to be considered in local adaptation of the generic instruments. Illustrative results from research using this approach in Lao PDR are presented to demonstrate the effect of social factors on how people interact with animals. We believe that the expanded model can be similarly operationalized to explore the interactions of other social and policy-level determinants that may influence transmission of zoonoses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study

    Science.gov (United States)

    Mulak, Agata; Taché, Yvette

    2011-01-01

    Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response. PMID:21860814

  6. Application of mid-frequency ventilation in an animal model of lung injury: a pilot study.

    Science.gov (United States)

    Mireles-Cabodevila, Eduardo; Chatburn, Robert L; Thurman, Tracy L; Zabala, Luis M; Holt, Shirley J; Swearingen, Christopher J; Heulitt, Mark J

    2014-11-01

    Mid-frequency ventilation (MFV) is a mode of pressure control ventilation based on an optimal targeting scheme that maximizes alveolar ventilation and minimizes tidal volume (VT). This study was designed to compare the effects of conventional mechanical ventilation using a lung-protective strategy with MFV in a porcine model of lung injury. Our hypothesis was that MFV can maximize ventilation at higher frequencies without adverse consequences. We compared ventilation and hemodynamic outcomes between conventional ventilation and MFV. This was a prospective study of 6 live Yorkshire pigs (10 ± 0.5 kg). The animals were subjected to lung injury induced by saline lavage and injurious conventional mechanical ventilation. Baseline conventional pressure control continuous mandatory ventilation was applied with V(T) = 6 mL/kg and PEEP determined using a decremental PEEP trial. A manual decision support algorithm was used to implement MFV using the same conventional ventilator. We measured P(aCO2), P(aO2), end-tidal carbon dioxide, cardiac output, arterial and venous blood oxygen saturation, pulmonary and systemic vascular pressures, and lactic acid. The MFV algorithm produced the same minute ventilation as conventional ventilation but with lower V(T) (-1 ± 0.7 mL/kg) and higher frequency (32.1 ± 6.8 vs 55.7 ± 15.8 breaths/min, P ventilation and MFV for mean airway pressures (16.1 ± 1.3 vs 16.4 ± 2 cm H2O, P = .75) even when auto-PEEP was higher (0.6 ± 0.9 vs 2.4 ± 1.1 cm H2O, P = .02). There were no significant differences in any hemodynamic measurements, although heart rate was higher during MFV. In this pilot study, we demonstrate that MFV allows the use of higher breathing frequencies and lower V(T) than conventional ventilation to maximize alveolar ventilation. We describe the ventilatory or hemodynamic effects of MFV. We also demonstrate that the application of a decision support algorithm to manage MFV is feasible. Copyright © 2014 by Daedalus Enterprises.

  7. Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

    Science.gov (United States)

    Trevizol, Fabiola; Benvegnú, Dalila M; Barcelos, Raquel C S; Pase, Camila S; Segat, Hecson J; Dias, Verônica Tironi; Dolci, Geisa S; Boufleur, Nardeli; Reckziegel, Patrícia; Bürger, Marilise E

    2011-08-01

    Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  9. REAC regenerative treatment efficacy in experimental chondral lesions: a pilot study on ovine animal model

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    Sanna Passino E

    2017-09-01

    Full Text Available Eraldo Sanna Passino,1,2 Stefano Rocca,1 Sabrina Caggiu,1 Nicolò Columbano,1,2 Alessandro Castagna,3 Vania Fontani,3–5 Salvatore Rinaldi3–51Department of Veterinary Medicine, University of Sassari, Sassari, Italy; 2Comparative Surgery Research Laboratory, University of Sassari, Sassari, Italy; 3Department of Regenerative Medicine, Rinaldi Fontani Institute, Florence, Italy; 4Research Department, Rinaldi Fontani Foundation, Florence, Italy; 5Research Department, IRF Shanghai Biomedical Sciences, Shanghai, People’s Republic of China Abstract: Radioelectric asymmetric conveyor (REAC technology is a platform designed to optimize cell polarity. Cell polarity is a universal biological phenomenon that is implicated in cell differentiation, proliferation, morphogenesis, aging, and rejuvenation. In this work, we investigate a timing and administration protocol for tissue optimization regenerative treatment type C, in order to treat aging-related chondral damage or injuries and gain insights into regenerative processes of articular cartilage in humans. The chondral lesion produced in this study in an animal model (6 knee joints of 4 adult sheep was 6 mm in diameter and about 2 mm deep. These lesions, which did not involve subchondral bone, tend to increase in size and depth and are not completely repaired with normal hyaline articular cartilage since adult articular cartilage is avascular and has a very slow turnover at the cellular and molecular level. Moreover, the hydration of articular cartilage is reduced with aging and with decreased mitotic activity, synthesis, and population size of chondrocytes. Six months posttreatment, lesions appeared filled, though not completely, with newly generated tissue of the light opalescent color of healthy articular cartilage, which otherwise covered the underlying subchondral bone. The newly formed tissue surface appeared to be quite regular. Nearly complete regeneration of subchondral bone occurred, with

  10. 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...

  11. 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

  12. Pharmacological studies of ethanolic extracts of Maytenus rigida Mart (Celastraceae in animal models

    Directory of Open Access Journals (Sweden)

    Vanda Lucia dos Santos

    Full Text Available The crude ethanol extract (EEOH of the bark of Maytenus rigida Mart (Celastraceae a plant used in Brazil herbal traditional medicine, was tested for anti-inflammatory, antiulcer and antidiarrhoeal activities in animal models. No acute toxicological sign was observed in animals treated with the highest dose (5000 mg/kg, p.o. or 2000 mg/kg i.p. of EEOH. The extract doses of 250, 500 or 750 mg/kg revealed a significant inhibitory effect (P < 0,01 in carrageenin-induced rat paw oedema and exhibited ulcer-protective properties against ethanol-induced ulceration in rats. An anti-diarrhoeal activity (P < 0.01 was also observed in castor-oil-induced diarrhoeal in mice. The intestinal transit was significantly (P < 0.01 reduced, however the pretreatment did not reduce the weight of intestinal contents. These results support the popular applications of Maytenus rigida for the treatment of inflammation, ulcer and diarrhoea in Brazil herbal traditional medicine.

  13. Animal Models of Cardiovascular Diseases

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    Carlos Zaragoza

    2011-01-01

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

  14. 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.

  15. Spatial navigation: implications for animal models, drug development and human studies

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Kubík, Štěpán; Vlček, Kamil; Valeš, Karel

    2014-01-01

    Roč. 63, Suppl.1 (2014), S237-S249 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP303/12/1464; GA MZd(CZ) NT13386; GA MZd(CZ) NT13403; GA ČR(CZ) GA14-03627S Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204; EC(XE) PIR06-GA/2009-256581 Institutional support: RVO:67985823 Keywords : behavior * rat * animal models Subject RIV: FH - Neurology Impact factor: 1.293, year: 2014

  16. 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....

  17. An optimized animal model for partial and total skin thickness burns studies Um modelo animal aperfeiçoado para estudo de queimaduras superficiais e profundas da pele

    Directory of Open Access Journals (Sweden)

    Ana Paula Bomfim Soares Campelo

    2011-01-01

    Full Text Available PURPOSE: Development of an improved animal model for studying skin burns in rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6: G1-Control, G2- T100°C, G3-T150°C and G4-T200°C. Two 10 x 10 mm squares were outlined with a sterile surgical marker on each side and along the vertebral column using a prepared template positioned between the anterior and posterior limbs. G2-G4 rats were subjected to 100°C, 150°C and 200ºC thermal burns, respectively. G1 rats served as controls. Burns were inflicted by applying a copper plate connected to an electronic temperature controlling device to the dorsal skin of anesthetized rats. Four burns were produced on each animal (total area: 4 cm²/animal leaving about 1 cm of undamaged skin between burn areas. Analgesia was administered during 24 h after burn injury by adding 30 mg codeine phosphate hemihydrate to 500 ml tap water. RESULTS: The application of 100°C and 150ºC resulted in partial thickness skin burns with central reepithelialization of the burned area only at 100°C. In G4 group the whole thickness of the skin was injured without central reepithelialization. However, there was marginal reepithelialization in all groups. CONCLUSION: The model studied is inexpensive and easily reproducible, enabling the achievement of controlled burns with partial or total impairment of the skin in experimental animals.OBJETIVO: Desenvolvimento de um modelo animal aperfeiçoado para estudo de queimaduras cutâneas em ratos. MÉTODOS: Vinte e quatro ratos Wistar, machos, foram distribuídos aleatoriamente em quatro grupos (n=6: G1-Controle, G2-T100°C, G3-T150°C e G4-T200°C. Dois quadrados medindo 10x10 mm foram delineados com um marcador cirúrgico estéril em cada lado e ao longo da coluna vertebral e posicionados entre os membros anteriores e posteriores, utilizando um molde previamente preparado. Os ratos dos grupos G2-G4 foram submetidos a queimaduras térmicas de 100

  18. 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.

  19. 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.

  20. 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."

  1. 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.

  2. Study of crotoxin on the induction of paralysis in extraocular muscle in animal model

    Directory of Open Access Journals (Sweden)

    Geraldo de Barros Ribeiro

    2012-10-01

    Full Text Available PURPOSE: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A. METHODS: The crotoxin, with LD50 of 1.5 µg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 µg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. RESULTS: The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 µg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 µg. CONCLUSION: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 µg was able to induce similar effects as botulinum toxin type A.

  3. 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

  4. 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.

  5. Clinical implications of studies with MnDPDP in animal models of hepatic abnormalities

    International Nuclear Information System (INIS)

    Ni, Y.; Marchal, G.

    1997-01-01

    Mangafodipir trisodium (manganese dipyridoxal diphosphate or MnDPDP) has been introduced as a hepatobiliary MR contrast agent (Teslascan). It is potential to assist in the characterisation of focal liver lesions, the diagnosis of local and global obstructive cholestasis and the evaluation of hepatic function in diffuse liver diseases has been explored in multiple pre-clinical experiments with appropriate animal models. The prompt negative contrast enhancement and delayed pertumoural rim-enhancement seen after i.v. injection of MnDPDP are 2 typical features of primary and secondary liver tumours with high malignancy, while the persistent positive enhancement is a sign of liver tumours of well preserved hepatocitic nature. Liver with local and total biliary obstruction can be visualized in MnDPDP-enhanced MR images as a region with prolonged signal enhancement. This agent could also be used to non-invasively evaluate diffuse liver diseases of different causes. In the present paper, we review the experimental data in the literature, provide some unpublished results and discuss the potential impact on the clinical use of MnDPDP in the liver. We conclude that MnDPDP is a promising MR liver contrast agent for the detection and characterisation of focal and diffuse liver diseases. (orig.)

  6. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    International Nuclear Information System (INIS)

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

    1990-01-01

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

  7. Modeling the Responses to Resistance Training in an Animal Experiment Study

    Directory of Open Access Journals (Sweden)

    Antony G. Philippe

    2015-01-01

    Full Text Available The aim of the present study was to test whether systems models of training effects on performance in athletes can be used to explore the responses to resistance training in rats. 11 Wistar Han rats (277 ± 15 g underwent 4 weeks of resistance training consisting in climbing a ladder with progressive loads. Training amount and performance were computed from total work and mean power during each training session. Three systems models relating performance to cumulated training bouts have been tested: (i with a single component for adaptation to training, (ii with two components to distinguish the adaptation and fatigue produced by exercise bouts, and (iii with an additional component to account for training-related changes in exercise-induced fatigue. Model parameters were fitted using a mixed-effects modeling approach. The model with two components was found to be the most suitable to analyze the training responses (R2=0.53; P<0.001. In conclusion, the accuracy in quantifying training loads and performance in a rodent experiment makes it possible to model the responses to resistance training. This modeling in rodents could be used in future studies in combination with biological tools for enhancing our understanding of the adaptive processes that occur during physical training.

  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. A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

    Science.gov (United States)

    Rouleau, Pascal; Guertin, Pierre A

    2013-01-01

    Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

  10. Animal models for studies of chromosome aberration induction in PHA-stimulated lymphocytes

    International Nuclear Information System (INIS)

    Liniecki, J.; Bajerska, A.; Wyszynskaa, K.

    1978-01-01

    To assess the appropriate time for harvesting cultures of rabbit and swine lymphocytes, whole blood of these animals was irradiated with 300 rad γ-rays and microcultures were established using Ham's F-10 medium. Mitotic and tetraploidy indices, dicentrics per cell and the percentage of dicentric or ring-carrying cells, unaccompanied by acentrics, were determined as a function of culture duration. The same procedure was applied to human blood. The percentage of cells in first and second mitosis was determined in rabbit and swine lymphocyte cultures at selected times after stimulation using the FPG technique for differential staining of sister chromatids. The first mitotic waves appear at 30 +- 1, 36 +- 2, and 45 +- 1 h after PHA stimulation for pig, rabbit and man respectively. Correspondingly, in the three species a significant percentage of cells in second mitosis is already present by 36, 44 and 48 to 52 h and is accompanied by a steep reduction in the dicentric yields. These proposed culture times for rabbit and swine lymphocytes are shorter than those at which the majority of relevant studies reported in the literature have been performed. (author)

  11. Systems approach to studying animal sociality: individual position versus group organization in dynamic social network models.

    Directory of Open Access Journals (Sweden)

    Karlo Hock

    2010-12-01

    Full Text Available Social networks can be used to represent group structure as a network of interacting components, and also to quantify both the position of each individual and the global properties of a group. In a series of simulation experiments based on dynamic social networks, we test the prediction that social behaviors that help individuals reach prominence within their social group may conflict with their potential to benefit from their social environment. In addition to cases where individuals were able to benefit from improving both their personal relative importance and group organization, using only simple rules of social affiliation we were able to obtain results in which individuals would face a trade-off between these factors. While selection would favor (or work against social behaviors that concordantly increase (or decrease, respectively fitness at both individual and group level, when these factors conflict with each other the eventual selective pressure would depend on the relative returns individuals get from their social environment and their position within it. The presented results highlight the importance of a systems approach to studying animal sociality, in which the effects of social behaviors should be viewed not only through the benefits that those provide to individuals, but also in terms of how they affect broader social environment and how in turn this is reflected back on an individual's fitness.

  12. Animal studies on Spacelab-3

    Science.gov (United States)

    Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.

    1987-01-01

    The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

  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. Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs.

    Science.gov (United States)

    Risal, Sanjiv; Adhikari, Deepak; Liu, Kui

    2016-01-01

    Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

  15. Animal models for studying neural crest development: is the mouse different?

    Science.gov (United States)

    Barriga, Elias H; Trainor, Paul A; Bronner, Marianne; Mayor, Roberto

    2015-05-01

    The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems. © 2015. Published by The Company of Biologists Ltd.

  16. PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery.

    Science.gov (United States)

    Renz, Bernhard W; Leitner, Kurt; Odermatt, Erich; Worthley, Daniel L; Angele, Martin K; Jauch, Karl-Walter; Lang, Reinhold A

    2014-03-01

    Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model. Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed. All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs. These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.

  17. The conscious pig as a large animal model for studies of hemorrhagic hypotension

    International Nuclear Information System (INIS)

    Hannon, J.P.; Bossone, C.A.

    1986-01-01

    Seven to 10 days after chronic implantation of carotia artery cannulae, conscious pigs (20 to 25 kg), while in an unrestrained near basal state, were subjected to 30 or 50% hemorrhage (N = 6/group) of the estimated blood volume over a one hr period. Absolute blood losses averaged 23.1 and 38.5 ml/kg. All pigs survived these insults; the only untoward effects were dizziness, nausea and vomiting near the end of bleeding in the 50% group. Heart rates were unaltered during hemorrhage but over a subsequent five hr period of spontaneous recovery mild tachycardia, from 104 ''+ or -'' 7.2 and 135 ''+ or -'' 5.1 beats/min, was recorded in animals subjected to 50% blood loss. Mean arterial pressures during hemorrhage decreased from 115 ''+ or -'' 2.7 to 79 ''+ or -'' 3.7 mm Hg in the 30% group and from 105 ''+ or -'' 2.2 to 46 ''+ or -'' 3.5 mm Hg in the 50% group. After five hr recovery, respective values were 105 ''+ or -'' 4.2 and 81 ''+ or -'' 1.8 mm Hg. Transcapillary refill was evidenced in both hemorrhage conditions by a decrease in hematocrit values, particularly during the recovery period. Hemorrhage and subsequent recovery, in the 50% but not the 30% group, was associated with transient hyperglycemia, hyperlactacidemia, hypocapnia, elevated base deficit, hyperoxemia and hypokalemia. These animals also showed transient plasma magnesium and creatine increments and a progressively more pronounced uremia. Plasma sodium, chloride and phosphate levels were unaffected

  18. Animal Models in Studies of Cardiotoxicity Side Effects from Antiblastic Drugs in Patients and Occupational Exposed Workers

    Directory of Open Access Journals (Sweden)

    Monica Lamberti

    2014-01-01

    Full Text Available Cardiotoxicity is an important side effect of cytotoxic drugs and may be a risk factor of long-term morbidity for both patients during therapy and also for staff exposed during the phases of manipulation of antiblastic drugs. The mechanism of cardiotoxicity studied in vitro and in vivo essentially concerns the formation of free radicals leading to oxidative stress, with apoptosis of cardiac cells or immunologic reactions, but other mechanisms may play a role in antiblastic-induced cardiotoxicity. Actually, some new cytotoxic drugs like trastuzumab and cyclopentenyl cytosine show cardiotoxic effects. In this report we discuss the different mechanisms of cardiotoxicity induced by antiblastic drugs assessed using animal models.

  19. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Science.gov (United States)

    Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

    2007-07-27

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  20. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Directory of Open Access Journals (Sweden)

    Eleftherios Mylonakis

    2007-07-01

    Full Text Available Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  1. From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD).

    Science.gov (United States)

    Eilam, David

    2017-05-01

    The application of similar analyses enables a direct projection from translational research in animals to human studies. Following is an example of how the methodology of a specific animal model of obsessive-compulsive disorder (OCD) was applied to study human patients. Specifically, the quinpirole rat model for OCD was based on analyzing the trajectories of travel among different locales, and scoring the set of acts performed at each locale. Applying this analytic approach in human patients unveiled various aspects of OCD, such as the repetition and addition of acts, incompleteness, and the link between behavior and specific locations. It is also illustrated how the same analytical approach could be applicable to studying other mental disorders. Finally, it is suggested that the development of OCD could be explained by the four-phase sequence of Repetition, Addition, Condensation, and Elimination, as outlined in the study of ontogeny and phylogeny and applied to normal development of behavior. In OCD, this sequence is curtailed, resulting in the abundant repetition and addition of acts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Animal Studies of Addictive Behavior

    Science.gov (United States)

    Ahmed, Serge H.

    2013-01-01

    It is increasingly recognized that studying drug taking in laboratory animals does not equate to studying genuine addiction, characterized by loss of control over drug use. This has inspired recent work aimed at capturing genuine addiction-like behavior in animals. In this work, we summarize empirical evidence for the occurrence of several DSM-IV-like symptoms of addiction in animals after extended drug use. These symptoms include escalation of drug use, neurocognitive deficits, resistance to extinction, increased motivation for drugs, preference for drugs over nondrug rewards, and resistance to punishment. The fact that addiction-like behavior can occur and be studied in animals gives us the exciting opportunity to investigate the neural and genetic background of drug addiction, which we hope will ultimately lead to the development of more effective treatments for this devastating disorder. PMID:23249442

  4. 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

  5. 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.

  6. Studies on anti-inflammatory and analgesic properties of Lactobacillus rhamnosus in experimental animal models.

    Science.gov (United States)

    Amdekar, Sarika; Singh, Vinod

    2016-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment of inflammatory diseases. However, constant use of NSAID may lead to some side effects like gastrointestinal ulcers, bleeding and renal disorders. This study evaluates analgesic and anti-inflammatory activities of Lactobacillus rhamnosus in female Wistar rats. Diclofenac sodium was used as a standard drug for comparison. L. rhamnosus, drugs and vehicle were administered orally. Acetic acid-induced writhing test and carrageenan-induced paw edema model were used for evaluation. Paw edema and number of writhes were measured subsequently. Pro-inflammatory (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines were estimated in serum after 24 h. Results showed that L. rhamnosus significantly decreased the paw thickness at t=24 h by 28.66 % while drug decreased by 19.33 %. Also, L. rhamnosus treatment and standard drug showed a protection of 66.66 % and 41.66 %, respectively. L. rhamnosus and diclofenac sodium treatment significantly down-regulated pro-inflammatory and up-regulated anti-inflammatory cytokines at prhamnosus was more pronounced in comparison to diclofenac sodium. The present study clearly suggests that L. rhamnosus suppressed carrageenan-induced paw edema after second phase and decreased the acetic acid-induced writhings. It ameliorated the inflammatory pathways by down-regulating pro-inflammatory cytokines. However, additional clinical investigations are needed to prove the efficacy of L. rhamnosus in treatment/management of inflammatory joint diseases.

  7. 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...

  8. Use of Transgenic and Mutant Animal Models in the Study of Heterocyclic Amine-induced Mutagenesis and Carcinogenesis

    Science.gov (United States)

    Dashwood, Roderick H.

    2008-01-01

    Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptΔ transgenics, XPA−/−, XPC−/−, Msh2+/−, Msh2−/− and p53+/− knock-outs, Apc mutant mice (ApcΔ716, Apc1638N, Apcmin), and A33ΔNβ-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac. PMID:12542973

  9. 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.

  10. An animal model for instructing and the study of in situ arterial bypass.

    Science.gov (United States)

    Saifi, J; Chang, B B; Paty, P S; Kaufman, J; Leather, R P; Shah, D M

    1990-11-01

    A canine model that used the cephalic vein to bypass from the brachial to the ulnar artery was designed for use in instructing and evaluating surgical technique needed for constructing an in situ arterial bypass. This model was used for instructing vascular residents in the in situ vein bypass technique. The use of this model enabled the resident to become more adept with the instruments for valve incision and construction of small vessel anastomosis. The improvement in the resident's operative technique was reflected by a decrease in the number of technical complications (missed valves, missed arteriovenous fistulas, poorly constructed anastomoses) and improved patency rate.

  11. Lemon Odor Reduces Stress-induced Neuronal Activation in the Emotion Expression System: An Animal Model Study

    Science.gov (United States)

    Sanada, Kazue; Sugimoto, Koji; Shutoh, Fumihiro; Hisano, Setsuji

    Perception of particular sensory stimuli from the surroundings can influence emotion in individuals. In an uncomfortable situation, humans protect themselves from some aversive stimulus by acutely evoking a stress response. Animal model studies have contributed to an understanding of neuronal mechanisms underlying the stress response in humans. To study a possible anti-stressful effect of lemon odor, an excitation of neurons secreting corticotropin-releasing hormone (CRH) as a primary factor of the hypothalamic-pituitary-adrenal axis (HPA) was analyzed in animal model experiments, in which rats are restrained in the presence or absence of the odor. The effect was evaluated by measuring expression of c-Fos (an excited neuron marker) in the hypothalamic paraventricular nucleus (PVN), a key structure of the HPA in the brain. We prepared 3 animal groups: Groups S, L and I. Groups S and L were restrained for 30 minutes while being blown by air and being exposed to the lemon odor, respectively. Group I was intact without any treatment. Two hours later of the onset of experiments, brains of all groups were sampled and processed for microscopic examination. Brain sections were processed for c-Fos immunostaining and/or in situ hybridization for CRH. In Group S but not in Group I, c-Fos expression was found in the PVN. A combined in situ hybridization-immunohistochemical dual labeling revealed that CRH mRNA-expressing neurons express c-Fos. In computer-assisted automatic counting, the incidence of c-Fos-expressing neurons in the entire PVN was statistically lower in Group L than in Group S. Detailed analysis of PVN subregions demonstrated that c-Fos-expressing neurons are fewer in Group L than in Group S in the dorsal part of the medial parvocellular subregion. These results may suggest that lemon odor attenuates the restraint stress-induced neuronal activation including CRH neurons, presumably mimicking an aspect of stress responses in humans.

  12. Development of a diagnostic model for inhaled promethium-147 oxide. Animal studies

    International Nuclear Information System (INIS)

    Shipler, D.B.; Ballou, J.E.; Griffin, B.I.; Nelson, I.C.

    1976-01-01

    Rats and beagles were exposed by inhalation to an aerosol containing stable Sm 2 O 3 tagged with 145 Sm 2 O 3 and 143 Pm 2 O 3 . The animals were sacrificed at 0, 14 and 30 days post-exposure to compare the kinetics and translocation of 145 Sm and 143 Pm. Quantitative analysis for 145 Sm and 143 Pm in several tissues and excreta indicate that the two rare-earth elements were mobilized and distributed similarly by the rats and dogs. Results indicate that within the error of the measurement technique, samarium acts as a carrier for promethium. The data also indicate that activities measured in faecal samples could be used to predict lung burdens of 147 Pm. At activity levels and sintering temperatures employed in the rat exposures, there was sufficient activity in urine samples to permit its use as an indicator of lung burdens of 147 Pm. At activity levels and sintering temperatures employed in the dog exposures, this was not the case. (author)

  13. Development of a diagnostic model for inhaled promethium-147 oxide: animal studies

    International Nuclear Information System (INIS)

    Shipler, D.B.; Ballou, J.E.; Griffin, B.I.; Nelson, I.C.

    1975-01-01

    Rats and beagle dogs were exposed by inhalation to an aerosol containing stable Sm 2 O 3 tagged with 145 Sm 2 O 3 and 143 Pm 2 O 3 . The animals were sacrificed at 0, 14 and 30 days post-exposure to compare the kinetics and translocation of 145 Sm and 143 Pm. Quantitative analysis for 145 Sm and 143 Pm in several tissues and excreta indicate that the two rare earth elements were mobilized and distributed similarly by the rats and dogs. Results indicate that within the error of the measurement technique, samarium acts as a carrier for promethium. The data also indicate that activities measured in fecal samples could be used to predict lung burdens of 147 Pm. At activity levels and sintering temperatures employed in the rat exposures, there was sufficient activity in urine samples to permit its use as an indicator of lung burdens of 147 Pm. At activity levels and sintering temperatures employed in the dog exposures, this was not the case. (auth)

  14. 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

  15. Feasibility Study of a Standardized Novel Animal Model for Cervical Vertebral Augmentation in Sheep Using a PTH Derivate Bioactive Material

    Directory of Open Access Journals (Sweden)

    Karina Klein

    2014-08-01

    Full Text Available Prophylactic local treatment involving percutaneous vertebral augmentation using bioactive materials is a new treatment strategy in spine surgery in humans for vertebral bodies at risk. Standardized animal models for this procedure are almost non-existent. The purpose of this study was to: (i prove the efficacy of PTH derivate bioactive materials for new bone formation; and (ii create a new, highly standardized cervical vertebral augmentation model in sheep. Three different concentrations of a modified form of parathyroid hormone (PTH covalently bound to a fibrin matrix containing strontium carbonate were used. The same matrix without PTH and shams were used as controls. The bioactive materials were locally injected. Using a ventral surgical approach, a pre-set amount of material was injected under fluoroscopic guidance into the intertrabecular space of three vertebral bodies. Intravital fluorescent dyes were used to demonstrate new bone formation. After an observation period of four months, the animals were sacrificed, and vertebral bodies were processed for µCT, histomorphometry, histology and sequential fluorescence evaluation. Enhanced localized bone activity and new bone formation in the injected area could be determined for all experimental groups in comparison to the matrix alone and sham with the highest values detected for the group with a medium concentration of PTH.

  16. A study of the anti-inflammatory effect of the leaves of Psidium guajava Linn. on experimental animal models

    Science.gov (United States)

    Dutta, Sarmistha; Das, Swarnamoni

    2010-01-01

    Introduction: The aim is to study the anti-inflammatory effect of the ethanolic extract of the leaves of Psidium guajava(PGE) on experimental animal models. Materials and Methods: Fresh leaves were collected, air-dried, powdered, and percolated in 95% ethanol. Acute toxicity test was done according to OECD guidelines. Four groups of animals of either sex, weighing 150–200g of the species Rattus norvegicus were taken for the study (n = 6). Group A was taken as control (3% gum acacia in 10 mL/kg body weight), Group B as test group (PGE 250 mg/kg body weight), Group C as test group (PGE 500 mg/kg body weight), and Group D as standard (Aspirin 100 mg/kg body weight). The animals were studied for acute inflammation by Carrageenan-induced rat paw edema, subacute inflammation by Granuloma pouch method, and chronic inflammation by Freund’s adjuvant-induced arthritis method. Statistical analysis was done by one-way analysis of variance followed by multiple comparison tests. Results: In acute inflammation, there was significant inhibition of paw edema in Groups B, C, and D in comparison with Group A (P < 0.05). In subacute inflammation, there was significant inhibition of exudate formation in Groups B, C, and D in comparison to Group A (P < 0.05). In chronic inflammation, there was significant inhibition of paw edema and inhibition of weight reduction in Groups B, C, and D compared with Group A. Downregulation of arthritis index was also significant in Groups B, C, and D in comparison with Group A (P < 0.05). Conclusion: The ethanolic extract of PGE has significant anti-inflammatory activity. PMID:21589759

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

    Science.gov (United States)

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

    2015-03-01

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

  18. The Pig as a Large Animal Model for Studying Anti-Tumor Immune Responses

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr

    but also generates a selective pressure, which may lead to selection of tumor cell variants with reduced immunogenicity; thereby, increasing the risk of tumor escape. Cancer immunotherapy includes treatment strategies aimed at activating anti-tumor immune responses or inhibiting suppressive and tumor......-favorable immune mechanisms. One of the promising arms of cancer immunotherapy is peptide-based therapeutic vaccines; yet, no such vaccine has been approved for use in human oncology. For many years, mouse models have provided invaluable understanding of complex immunological pathways; however, the majority...... tolerance towards IDO and the establishment of an antigen-specific cell-mediated immune (CMI) response. When comparing the different CAF09-formulated antigen doses, we demonstrate the induction of a CMI-dominant response upon exposure to a low endogenous peptide dose. In contrast, a mixed CMI and humoral...

  19. 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.

  20. 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

    NARCIS (Netherlands)

    Vries, R.B.M. de; Buma, P.; Leenaars, M.; Ritskes-Hoitinga, M.; Gordijn, B.

    2012-01-01

    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

  1. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Science.gov (United States)

    Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

  2. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Directory of Open Access Journals (Sweden)

    Koert J. Stittelaar

    2016-06-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo. Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50 administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI. Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

  3. Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

    Directory of Open Access Journals (Sweden)

    D.S. Macêdo

    2012-03-01

    Full Text Available Prenatal immune challenge (PIC in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C, to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge for original studies published in the last 10 years (May 2001 to October 2011 concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

  4. Dynamic contrast-enhanced MRI examination of atherosclerotic plaques: an animal study using rabbit model

    International Nuclear Information System (INIS)

    Li Mingli; Sun Jie; Chang Xiaoyan; Jin Zhengyu

    2011-01-01

    Objective: The enhanced patterns of atherosclerotic plaque on dynamic contrast- enhanced MRI have not been well studied. The aim of this study was to explore the patterns of plaque enhancement and their underlying mechanism by using dynamic contrast-enhanced MRI (DCE-MRI). Methods: Atherosclerotic plaques were induced in the aorta of 12 New Zealand White rabbits by a combination of endothelial denudation and high-cholesterol diet. Ten to sixteen weeks after surgery, DCE- MRI was performed with a fast spin echo T 1 weighted sequence. Thirty-five phases of images were obtained at 71-second intervals. Gd-DTPA was injected coincident with the third scan via marginal ear vein. Specimens were harvested within 12 hours after imaging for HE staining and CD31 immunohistochemical staining which was used to highlight neo-vessels. Plaque enhancement patterns were studied and compared with histological findings. Signal intensity of each plaque section was normalized to pre-contrast signal intensity of psoas muscle, after which signal intensity versus time curve was drawn. Pearson correlation coefficient was used to reveal association between histological neo-vessel count and descriptive parameters derived from signal intensity versus time curve. Results: Plaques were significantly enhanced by Gd-DTPA. Enhancement patterns could be described as 'fast-in and slow-out'. Differences in patterns of enhancement were observed between tissues, with fibrous tissue enhanced more than lipid aggregation and leukocyte foci. Peak enhancement (1.05±0.30), initial slope (0.82±0.28) and area under the curve at early phase (4.97± 1.67) derived from signal intensity-time curve had significant correlations with neo-vessel count (117.7± 93.3) (r=0.553, 0.468, 0.554 respectively, P<0.05). Conclusions: The enhanced patterns of atherosclerotic plaque by Gd-DTPA were 'fast- in and slow-out'. Neovascularization, increased endothelial permeability and extracellular matrix may be the reasons for

  5. The use of non-human primates as animal models for the study of hepatitis viruses

    Directory of Open Access Journals (Sweden)

    C.L. Vitral

    1998-08-01

    Full Text Available Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

  6. Nephro-protective potential of Morus alba, a prospective experimental study on animal models.

    Science.gov (United States)

    Ullah, Naveed; Khan, Mir Azam; Khan, Salimullah; Ahmad, Habib; Asif, Afzal Haq; Khan, Taous

    2016-01-01

    Morus alba L. (Moraceae) is traditionally used for the treatment of urinary incontinency due its strong diuretic properties. The present study explores the renal protective effects of M. alba, due to its free radical scavenging properties, in order to provide experimental evidence for its established use. Ethanolic extract (200 mg/kg/d) derived from M. alba fruit was employed in rabbits as a co-therapy (GM-al) with gentamicin (80 mg/kg/d) for a period of 3 weeks. Biochemical kidney functioning parameters, urinary isozymes, and histopathological examination were performed. The results showed that ethanol extract of Morus alba L. prevented alterations in serum creatinine (4.02 ± 0.14, p alba with gentamicin prevented renal functioning alterations expected with the use of gentamicin alone. Therefore, it can be concluded that M. alba to protect from kidney damage, which may be because of its free radical scavenging and diuretic properties.

  7. Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

    Science.gov (United States)

    Dixon, C. Edward

    2011-06-01

    Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

  8. 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

  9. 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.

  10. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    Science.gov (United States)

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  11. Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication.

    Directory of Open Access Journals (Sweden)

    Brittany M Ashlock

    Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.

  12. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  13. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The

  14. 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...

  15. 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...

  16. Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

    Science.gov (United States)

    Hammoum, Imane; Benlarbi, Maha; Dellaa, Ahmed; Szabó, Klaudia; Dékány, Bulcsú; Csaba, Dávid; Almási, Zsuzsanna; Hajdú, Rozina I; Azaiz, Rached; Charfeddine, Ridha; Lukáts, Ákos; Ben Chaouacha-Chekir, Rafika

    2017-09-01

    The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases. © 2017 Wiley Periodicals, Inc.

  17. 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.

  18. 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.

  19. A Disposable Tear Glucose Biosensor-Part 4: Preliminary Animal Model Study Assessing Efficacy, Safety, and Feasibility.

    Science.gov (United States)

    La Belle, Jeffrey T; Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R; Cook, Curtiss B

    2014-01-01

    A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R 2 = .7544). The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. © 2014 Diabetes Technology Society.

  20. Comparative dual-tracer studies of carbon-14 tryptophan and iodine-131 HIPDM in animal models of pancreatic diseases

    International Nuclear Information System (INIS)

    Kubota, K.; Som, P.; Brill, A.B.; Sacker, D.F.; Meinken, G.E.; Srivastava, S.C.; Atkins, H.L.

    1989-01-01

    Our previous studies have shown that a significant amount of the diamine derivative 131 I-N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) is taken up and retained by the normal pancreas. Therefore, we studied the uptake of [ 13 1I]HIPDM in various pathophysiological models in mice (chronic alcoholism, diabetes with beta-cell atrophy and obesity with beta-cell hypertrophy) and compared to 14 C-L-Tryptophan (TRY) distribution in order to determine the factors influencing their pancreatic uptake. In normal animals, the pancreas uptake of TRY was generally higher than HIPDM. In diabetes, the relative concentration of both compounds was higher over the controls; however, in obesity, TRY showed lower accumulation than in controls while HIPDM showed no significant difference. Chronic ethanol (20%) ingestion increased TRY uptake in the pancreas compared to controls (36.88 ± 3.21 vs. 30.03 ± 4.17% ID/g; p less than 0.01) after 5 wk study period, but it decreased by 10 wk (22.36 ± 0.95% ID/g; p less than 0.005). There were no significant changes in [ 131 I]HIPDM distribution in alcoholics as compared to the controls. Radioiodinated HIPDM has potential advantages over [ 11 C]TRY for pancreatic imaging since conventional imaging techniques can be employed. Our data, however, suggest that 11 C-L-TRY is a more sensitive indicator of various pancreatic disorders

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

    Science.gov (United States)

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

    2018-03-01

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

  2. 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

  3. 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

  4. 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.

  5. 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.

  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. Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

    Directory of Open Access Journals (Sweden)

    Claus Henn Birgit

    2011-11-01

    Full Text Available Abstract Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation manganese concentrations were 17.0 (1.5 μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]. TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.

  8. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

    Science.gov (United States)

    Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K. M.; Gomez-Cabrera, M. C.; Vina, J.; Borras, C.

    2015-01-01

    Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol. PMID:26221416

  9. Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study

    Directory of Open Access Journals (Sweden)

    Bruna M. Ascoli

    2017-05-01

    Full Text Available Abstract Introduction The rationale of mesenchymal stem cells (MSCs as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX. Methods Wistar rats (n=65 received one oral daily dose of LDX (10 mg/kg or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells or lithium (47.5 mg/kg as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004, and lithium reversed LDX-related hyperactive behavior (p0.05 in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

  10. Characterizing ingestive behavior through licking microstructure: Underlying neurobiology and its use in the study of obesity in animal models.

    Science.gov (United States)

    Johnson, Alexander W

    2018-02-01

    Ingestive behavior is controlled by multiple distinct peripheral and central physiological mechanisms that ultimately determine whether a particular food should be accepted or avoided. As rodents consume a fluid they display stereotyped rhythmic tongue movements, and by analyzing the temporal distribution of pauses of licking, it is possible through analyses of licking microstructure to uncover dissociable evaluative and motivational variables that contribute to ingestive behavior. The mean number of licks occurring within each burst of licking (burst and cluster size) reflects the palatability of the consumed solution, whereas the frequency of initiating novel bouts of licking behavior (burst and cluster number) is dependent upon the degree of gastrointestinal inhibition that accrues through continued fluid ingestion. This review describes the analysis of these measures within a context of the behavioral variables that come to influence the acceptance or avoidance of a fluid, and the neurobiological mechanisms that underlie alterations in the temporal distribution of pauses of licks. The application of these studies to models of obesity in animals is also described. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  11. A Study of the Protective Effect of Triticum aestivum L. in an Experimental Animal Model of Chronic Fatigue Syndrome.

    Science.gov (United States)

    Borah, Mukundam; Sarma, Phulen; Das, Swarnamoni

    2014-10-01

    Oxidative stress plays a major role in the pathogenesis of chronic fatigue syndrome (CFS). Keeping in view the proven antioxidant activity of Triticum aestivum L., this study has been undertaken to explore the potential therapeutic benefit of this plant in the treatment of CFS. To study the protective effect of the ethanolic extract of the leaves of Triticum aestivum (EETA) in an experimental mice model of CFS. Five groups of albino mice (20-25 g) were selected for the study, with five animals in each group. Group A served as the naïve control and Group B served as the stressed control. Groups C and D received EETA (100 mg/kg and 200 mg/kg b.w.). Group E received imipramine (20 mg/kg b.w.). Except for Group A, mice in each group were forced to swim 6 min each for 7 days to induce a state of chronic fatigue. Duration of immobility was measured on every alternate day. After 7 days, various behavioral tests (mirror chamber and elevated plus maize test for anxiety, open field test for locomotor activity) and biochemical estimations (malondialdehyde [MDA] and catalase activity) in mice brain were performed. Forced swimming in the stressed group resulted in a significant increase in immobility period, decrease in locomotor activity and elevated anxiety level. The brain homogenate showed significantly increased MDA and decreased catalase levels. The extract-treated groups showed significantly (P < 0.05) improved locomotor activity, decreased anxiety level, elevated catalase levels and reduction of MDA. The study confirms the protective effects of EETA in CFS.

  12. 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

  13. 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

  14. 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

  15. Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design

    Directory of Open Access Journals (Sweden)

    Christina L. Hutson

    2015-01-01

    Full Text Available Monkeypox virus (MPXV infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8×103 p.f.u. with Congo Basin (CB or West African (WA MPXV, and 28 tissues were harvested on days 2, 4, 6, 9, 12, 17, and 24 postinfection. Samples were evaluated for the presence of virus and gross and microscopic lesions. Virus was recovered from nasal mucosa, oropharyngeal lymph nodes, and spleen earlier in CB challenged animals (day 4 than WA challenged animals (day 6. For both groups, primary viremia (indicated by viral DNA was seen on days 6–9 through day 17. CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity in animals compared to WA MPXV. Histopathology and immunohistochemistry (IHC findings, however, were similar. Two animals that succumbed to disease demonstrated abundant viral antigen in all organs tested, except for brain. Dual-IHC staining of select liver and spleen sections showed that apoptotic cells (identified by TUNEL tended to colocalize with poxvirus antigen. Interestingly splenocytes were labelled positive for apoptosis more often than hepatocytes in both MPXV groups. These findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying sites that are important during early viral replication and cellular response to viral infection.

  16. Bioavailability study of arsenic and mercury in traditional Chinese medicines (TCM) using an animal model after a single dose exposure.

    Science.gov (United States)

    Tinggi, Ujang; Sadler, Ross; Ng, Jack; Noller, Barry; Seawright, Alan

    2016-04-01

    Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague-Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2-7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. 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

  18. Initial study of sediment antagonism and characteristics of silver nanoparticle-coated biliary stents in an experimental animal model.

    Science.gov (United States)

    Tian, Yigeng; Xia, Mingfeng; Zhang, Shuai; Fu, Zhen; Wen, Qingbin; Liu, Feng; Xu, Zongzhen; Li, Tao; Tian, Hu

    2016-01-01

    Plastic biliary stents used to relieve obstructive jaundice are frequently blocked by sediment, resulting in loss of drainage. We prepared stents coated with silver nanoparticles (AgNPs) and compared their ability to resist sedimentation with Teflon stents in a beagle model of obstructive jaundice. AgNP-coated Teflon biliary stents were prepared by chemical oxidation-reduction and evaluated in an obstructive jaundice model that was produced by ligation of common bile duct (CBD); animals were randomized to two equal groups for placement of AgNP-coated or Teflon control stents. Liver function and inflammatory index were found to be similar in the two groups, and the obstruction was relieved. Stents were removed 21 days after insertion and observed by scanning and transmission electron microscopy. The AgNP coating was analyzed by energy dispersive X-ray analysis (EDXA), and the composition of sediment was assayed by Fourier-transform infrared (FTIR) spectroscopy. Electron microscopy revealed a black, closely adherent AgNP stent coating, with thicknesses of 1.5-6 µm. Sediment thickness and density were greater on Teflon than on AgNP-coated stents. EDXA confirmed the stability and integrity of the AgNP coating before and after in vivo animal experimentation. FTIR spectroscopy identified stent sediment components including bilirubin, cholesterol, bile acid, protein, calcium, and other substances. AgNP-coated biliary stents resisted sediment accumulation in this canine model of obstructive jaundice caused by ligation of the CBD.

  19. Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study.

    Directory of Open Access Journals (Sweden)

    Linda L Kusner

    Full Text Available The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.

  20. anyFish 2.0: An open-source software platform to generate and share animated fish models to study behavior

    Directory of Open Access Journals (Sweden)

    Spencer J. Ingley

    2015-12-01

    Full Text Available Experimental approaches to studying behaviors based on visual signals are ubiquitous, yet these studies are limited by the difficulty of combining realistic models with the manipulation of signals in isolation. Computer animations are a promising way to break this trade-off. However, animations are often prohibitively expensive and difficult to program, thus limiting their utility in behavioral research. We present anyFish 2.0, a user-friendly platform for creating realistic animated 3D fish. anyFish 2.0 dramatically expands anyFish’s utility by allowing users to create animations of members of several groups of fish from model systems in ecology and evolution (e.g., sticklebacks, Poeciliids, and zebrafish. The visual appearance and behaviors of the model can easily be modified. We have added several features that facilitate more rapid creation of realistic behavioral sequences. anyFish 2.0  provides a powerful tool that will be of broad use in animal behavior and evolution and serves as a model for transparency, repeatability, and collaboration.

  1. 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...

  2. 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.

  3. 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.

  4. Wound healing in cell studies and animal model experiments by low level laser therapy; Were clinical studies justified? A systematic review

    NARCIS (Netherlands)

    Lucas, C.; Criens-Poublon, L. J.; Cockrell, C. T.; de Haan, R. J.

    2002-01-01

    Based on results of cell studies and animal experiments, clinical trials with Low Level Laser Therapy (LLLT) were performed, which finally did not demonstrate a beneficial effect on outcome of wound healing. The aim of this study was to investigate whether the evidence from cell studies and animal

  5. Artificial vesicles as an animal cell model for the study of biological application of non-thermal plasma

    International Nuclear Information System (INIS)

    Ki, S H; Park, J K; Sung, C; Lee, C B; Uhm, H; Choi, E H; Baik, K Y

    2016-01-01

    Artificial cell-like model systems can provide information which is hard to obtain with real biological cells. Giant unilamellar vesicles (GUV) containing intra-membrane DNA or OH radical-binding molecules are used to visualize the cytolytic activity of OH radicals. Changes in the GUV membrane are observed by microscopy or flow cytometry as performed for animal cells after non-thermal plasma treatment. The experimental data shows that OH radicals can be detected inside the membrane, although the biological effects are not as significant as for H 2 O 2 . This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma. (paper)

  6. Initial study of sediment antagonism and characteristics of silver nanoparticle-coated biliary stents in an experimental animal model

    Directory of Open Access Journals (Sweden)

    Tian Y

    2016-04-01

    Full Text Available Yigeng Tian,1,* Mingfeng Xia,2,* Shuai Zhang,3 Zhen Fu,4 Qingbin Wen,2 Feng Liu,4 Zongzhen Xu,4 Tao Li,4 Hu Tian4 1Department of Physics, School of Physics and Technology, University of Jinan, Jinan, Shandong, People’s Republic of China; 2Department of Surgery, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Department of General Surgery, Sixth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 4Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objective: Plastic biliary stents used to relieve obstructive jaundice are frequently blocked by sediment, resulting in loss of drainage. We prepared stents coated with silver nanoparticles (AgNPs and compared their ability to resist sedimentation with Teflon stents in a beagle model of obstructive jaundice.Methods: AgNP-coated Teflon biliary stents were prepared by chemical oxidation–reduction and evaluated in an obstructive jaundice model that was produced by ligation of common bile duct (CBD; animals were randomized to two equal groups for placement of AgNP-coated or Teflon control stents. Liver function and inflammatory index were found to be similar in the two groups, and the obstruction was relieved. Stents were removed 21 days after insertion and observed by scanning and transmission electron microscopy. The AgNP coating was analyzed by energy dispersive X-ray analysis (EDXA, and the composition of sediment was assayed by Fourier-transform infrared (FTIR spectroscopy.Results: Electron microscopy revealed a black, closely adherent AgNP stent coating, with thicknesses of 1.5–6 µm. Sediment thickness and density were greater on Teflon than on AgNP-coated stents. EDXA confirmed the stability and integrity of the AgNP coating before and after in vivo animal experimentation. FTIR

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. Retinal Cell Degeneration in Animal Models

    Directory of Open Access Journals (Sweden)

    Masayuki Niwa

    2016-01-01

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

  12. 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.

  13. Uniaxial Tensile Properties of Atherosclerotic Carotid Artery After Mobilization of Pushing on Qiao-Gong: A Safety Study Using an Animal Model of Carotid Atherosclerosis.

    Science.gov (United States)

    Qi, Ji; Zhang, Shaoqun; Zhang, Lei; Ping, Ruiyue; Ping, Kaike; Ye, Da; Shen, Honggui; Chen, Yili; Li, Yikai

    2018-02-01

    This study aimed to preliminarily explore the effects of the soft tissue mobilization of pushing on Qiao-Gong (MPQ) on biomechanical properties of the carotid artery using an animal model of carotid atherosclerosis (CAS). Fifty rabbits were randomly divided into 4 groups: animals with CAS treated with MPQ (CAS-MPQ [n = 15]); animals with CAS treated without MPQ (CAS [n = 15]); normal animals treated with MPQ (normal-MPQ [n = 10]); and a blank control group (n = 10). The MPQ procedure consisted of soft tissue mobilization of the Qiao-Gong acupoint on the front edge of the sternocleidomastoid muscle applied from top to bottom, by flat pushing with the thumb repeatedly for 20 times. Disease in the CAS models was induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. At the end of modeling, carotid color Doppler ultrasonography examination was performed to confirm which animal models were successfully induced with CAS, excluding model rabbits without typical CAS at the same time. Then, MPQ was applied on rabbits in the CAS-MPQ and the normal-MPQ groups for 3 weeks. By contrast, rabbits in the other 2 groups were fed normally without MPQ. Uniaxial failure tests were later performed on carotid arteries in all 4 groups, and at the end of the study, a 2-way factorial analysis of variance of the results was conducted. (1) At the end of modeling, 10 rabbits in the CAS-MPQ group and 9 in the CAS group were included with typical carotid atherosclerotic characteristics. (2) Young's elastic modulus of the rabbit carotid artery increased more significantly in the CAS-MPQ group than the CAS group. (3) Compared with normal rabbit carotid arteries, atherosclerotic carotid arteries had lower levels of ultimate stress and ultimate strain but higher levels of ultimate load. The uniaxial tensile mechanical properties of the rabbit atherosclerotic carotid artery were impaired after MPQ. Copyright © 2018. Published by Elsevier Inc.

  14. Treatment of middle ear ventilation disorders: sheep as animal model for stenting the human Eustachian tube--a cadaver study.

    Directory of Open Access Journals (Sweden)

    Felicitas Miller

    Full Text Available Eustachian tube disorders can lead to chronic otitis media with consecutive conductive hearing loss. To improve treatment and to develop new types of implants such as stents, an adequate experimental animal model is required. As the middle ear of sheep is known to be comparable to the human middle ear, the dimensions of the Eustachian tube in two strains of sheep were investigated. The Eustachian tube and middle ear of half heads of heathland and blackface sheep were filled with silicone rubber, blended with barium sulfate to induce X-ray visibility. Images were taken by digital volume tomography. The tubes were segmented, and a three-dimensional model of every Eustachian tube was generated. The lengths, diameters and shapes were determined. Additionally, the feasibility of endoscopic stent implantation and fixation was tested in cadaver experiments. The length of the tube between ostium pharyngeum and the isthmus and the diameters were comparable to published values for the human tube. The tube was easily accessible through the nose, and then stents could be implanted and fixed at the isthmus. The sheep appears to be a promising model for testing new stent treatments for middle ear ventilation disorders.

  15. 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....

  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. 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.

  1. 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.

  2. 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

  3. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study

    Directory of Open Access Journals (Sweden)

    Rafati A.

    2015-09-01

    Full Text Available Introduction: The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog’s isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz. Materials and Methods: Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF radiation emitted from a common Jammer at a distance of 1m from the jammer’s antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T, the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz as stimuli. Results: The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. Conclusion: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

  4. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study.

    Science.gov (United States)

    Rafati, A; Rahimi, S; Talebi, A; Soleimani, A; Haghani, M; Mortazavi, S M J

    2015-09-01

    The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer's antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

  5. 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

  6. Imiquimod induced ApoE-deficient mice might be a composite animal model for the study of psoriasis and dyslipideamia comorbidity.

    Science.gov (United States)

    Xie, Xinran; Zhang, Lei; Lin, Yan; Wang, Yan; Liu, Weihong; Li, Xue; Li, Ping

    2017-10-01

    Psoriasis patients are at increased risk of developing lipid metabolism disturbances. Both psoriasis and dyslipideamia not only closely interact in disease development, but occur as mutual side effects in some medicine treatment. The interactive mechanism of the two diseases is complicated and still unclear. Here, we proposed applying imiquimod on the dorsal skin of ApoE -/- mice to establish a composite animal model which formed psoriasiform skin lesions under hyperlipidemic condition. By comparison with corresponding wild-type(C57BL/6) mice, the composite mice model was evaluated by skin pathological features, lipid levels, immune inflammatory factors in order to clarify the diseases interplay mechanism. In addition, IL-17 mAb treatment was applied to observe the effect of IL-17 antibody on the composite animal model. The results verified that imiquimod-induced ApoE -/- mice model presented keratinocyte hyperplasia, parakeratosis, inflammatory cells infiltration and elevated serum lipid levels, and also reflected the complex interaction between inflammation and lipid metabolism. IL-17 mAb could inhibit psoriasis skin lesions with lipid accumulation via STAT3 pathway, but no influence on elevated serum cholesterol. Imiquimod-induced ApoE -/- mice model presented the pathological features of psoriasis and dyslipideamia, which could be an ideal composite animal model for the study of pathogenesis and pharmacotherapeutics of psoriasis and dyslipideamia comorbidity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. 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

  8. A Preliminary Study of the Application of a Model Animal-Caenorhabidity elegans' Exposure to a Low-Energy Ion Irradiation System

    International Nuclear Information System (INIS)

    Liu Xuelan; Cai Kezhou; Feng Huiyun; Xu An; Yuan Hang; Yu Zengliang

    2007-01-01

    Because of the lack of suitable animal models adapted to high vacuum stress in the low-energy ion implantation system, the bio-effects ion irradiation with an energy less than 50 keV on multi-cellular animal individuals have never been investigated so far. The nematode Caenorhabditis elegans has proved to be an excellent animal model used for the study of a broad spectrum of biological issues. The purpose of this work was to investigate the viability of this animal under ion irradiation. We studied the protection effects of glycerol and trehalose on the enhancement of nematodes' ability to bear the vacuum stress. The results showed that the survival of the nematodes was enhanced remarkably under long and slow desiccation, even without glycerol and trehalose. 15% glycerol showed a better anti-vacuum stress effect on the nematodes than trehalose did under short-time desiccation. Low-temperature pre-treatment or post-treatment of the samples had no obvious effect on the survival scored after argon ion irradiation. Moreover, little effect was induced by 15% glycerol- and vacuum-exposure on germ cell apoptosis, compared to the untreated control sample. It issuggested that such treatment would provide relatively low background for genotoxic evaluations with ion irradiation

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  15. 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.

  16. 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....

  17. Bias During the Evaluation of Animal Studies?

    Science.gov (United States)

    Knight, Andrew

    2012-02-23

    My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  18. 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

  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. 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.

  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. Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting.

    Science.gov (United States)

    Trindade, Fábio; Leite-Moreira, Adelino; Ferreira-Martins, João; Ferreira, Rita; Falcão-Pires, Inês; Vitorino, Rui

    2017-02-01

    Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Physical and biological dosimetry at the RA-3 facility for small animal irradiation: preliminary BNCT studies in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Pozzi, Emiliano; Miller, Marcelo; Thorp, Silvia I.; Heber, Elisa M.; Trivillin, Veronica A.; Zarza, Leandro; Estryk, Guillermo; Schwint, Amanda E.; Nigg, David W.

    2007-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality based on the capture reaction that occurs between thermal neutrons and boron-10 atoms that accumulate selectively in tumor tissue, emitting high linear energy transfer (LET), short range (5-9 microns) particles (alpha y 7 Li). Thus, BNCT would potentially target tumor tissue selectively, sparing normal tissue. Herein we evaluated the feasibility of treating experimental oral mucosa tumors with BNCT at RA-3 (CAE) employing the hamster cheek pouch oral cancer model and characterized the irradiation field at the RA-3 facility. We evaluated the therapeutic effect on tumor of BNCT mediated by BPA in the hamster cheek pouch oral cancer model and the potential radio toxic effects in normal tissue. We evidenced a moderate biological response in tumor, with no radio toxic effects in normal tissue following irradiations with no shielding for the animal body. Given the sub-optimal therapeutic response, we designed and built a 6 Li 2 CO 3 shielding for the body of the animal to increase the irradiation dose to tumor, without exceeding normal tissue radio tolerance. The measured absolute magnitude of thermal neutron flux and the characterization of the beam with and without the shielding in place, suggest that the irradiation facility in the thermal column of RA-3 would afford an excellent platform to perform BNCT studies in vitro and in vivo in small experimental animals. The present findings must be confirmed and extended by performing in vivo BNCT radiobiological studies in small experimental animals, employing the shielding device for the animal body. (author) [es

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

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

    DEFF Research Database (Denmark)

    Damgaard, Lars Holm

    2007-01-01

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

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. Animal imaging studies of potential brain damage

    Science.gov (United States)

    Gatley, S. J.; Vazquez, M. E.; Rice, O.

    To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

  20. 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…

  1. Tribology studies of the natural knee using an animal model in a new whole joint natural knee simulator.

    Science.gov (United States)

    Liu, Aiqin; Jennings, Louise M; Ingham, Eileen; Fisher, John

    2015-09-18

    The successful development of early-stage cartilage and meniscus repair interventions in the knee requires biomechanical and biotribological understanding of the design of the therapeutic interventions and their tribological function in the natural joint. The aim of this study was to develop and validate a porcine knee model using a whole joint knee simulator for investigation of the tribological function and biomechanical properties of the natural knee, which could then be used to pre-clinically assess the tribological performance of cartilage and meniscal repair interventions prior to in vivo studies. The tribological performance of standard artificial bearings in terms of anterior-posterior (A/P) shear force was determined in a newly developed six degrees of freedom tribological joint simulator. The porcine knee model was then developed and the tribological properties in terms of shear force measurements were determined for the first time for three levels of biomechanical constraints including A/P constrained, spring force semi-constrained and A/P unconstrained conditions. The shear force measurements showed higher values under the A/P constrained condition (predominantly sliding motion) compared to the A/P unconstrained condition (predominantly rolling motion). This indicated that the shear force simulation model was able to differentiate between tribological behaviours when the femoral and tibial bearing was constrained to slide or/and roll. Therefore, this porcine knee model showed the potential capability to investigate the effect of knee structural, biomechanical and kinematic changes, as well as different cartilage substitution therapies on the tribological function of natural knee joints. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

    2011-10-01

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

  3. 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.

  4. 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...

  5. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

  7. 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

  8. 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 ...

  9. 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

  10. Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

    Directory of Open Access Journals (Sweden)

    Jessica Hoarau-Véchot

    2018-01-01

    Full Text Available An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

  11. Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

    Science.gov (United States)

    Hoarau-Véchot, Jessica; Rafii, Arash; Touboul, Cyril; Pasquier, Jennifer

    2018-01-18

    An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. Influence of Distal Resistance and Proximal Stiffness on Hemodynamics and RV Afterload in Progression and Treatments of Pulmonary Hypertension: A Computational Study with Validation Using Animal Models

    Directory of Open Access Journals (Sweden)

    Zhenbi Su

    2013-01-01

    Full Text Available We develop a simple computational model based on measurements from a hypoxic neonatal calf model of pulmonary hypertension (PH to investigate the interplay between vascular and ventricular measures in the setting of progressive PH. Model parameters were obtained directly from in vivo and ex vivo measurements of neonatal calves. Seventeen sets of model-predicted impedance and mean pulmonary arterial pressure (mPAP show good agreement with the animal measurements, thereby validating the model. Next, we considered a predictive model in which three parameters, PVR, elastic modulus (EM, and arterial thickness, were varied singly from one simulation to the next to study their individual roles in PH progression. Finally, we used the model to predict the individual impacts of clinical (vasodilatory and theoretical (compliance increasing PH treatments on improving pulmonary hemodynamics. Our model (1 displayed excellent patient-specific agreement with measured global pulmonary parameters; (2 quantified relationships between PVR and mean pressure and PVS and pulse pressure, as well as studiying the right ventricular (RV afterload, which could be measured as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves; (3 qualitatively confirmed the derangement of vascular wall shear stress in progressive PH; and (4 established that decreasing proximal vascular stiffness through a theoretical treatment of reversing proximal vascular remodeling could decrease RV afterload.

  17. 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.

  18. Bias During the Evaluation of Animal Studies?

    Directory of Open Access Journals (Sweden)

    Andrew Knight

    2012-02-01

    Full Text Available My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  19. 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.

  20. Angiographic analysis of animal model aneurysms treated with novel polyurethane asymmetric vascular stent (P-AVS): feasibility study.

    Science.gov (United States)

    Ionita, Ciprian N; Dohatcu, Andreea; Sinelnikov, Andrey; Sherman, Jason; Keleshis, Christos; Paciorek, Ann M; Hoffmann, K R; Bednarek, D R; Rudin, S

    2009-01-01

    Image-guided endovascular intervention (EIGI), using new flow modifying endovascular devices for intracranial aneurysm treatment is an active area of stroke research. The new polyurethane-asymmetric vascular stent (P-AVS), a vascular stent partially covered with a polyurethane-based patch, is used to cover the aneurysm neck, thus occluding flow into the aneurysm. This study involves angiographic imaging of partially covered aneurysm orifices. This particular situation could occur when the vascular geometry does not allow full aneurysm coverage. Four standard in-vivo rabbit-model aneurysms were investigated; two had stent patches placed over the distal region of the aneurysm orifice while the other two had stent patches placed over the proximal region of the aneurysm orifice. Angiographic analysis was used to evaluate aneurysm blood flow before and immediately after stenting and at four-week follow-up. The treatment results were also evaluated using histology on the aneurysm dome and electron microscopy on the aneurysm neck. Post-stenting angiographic flow analysis revealed aneurysmal flow reduction in all cases with faster flow in the distally-covered case and very slow flow and prolonged pooling for proximal-coverage. At follow-up, proximally-covered aneurysms showed full dome occlusion. The electron microscopy showed a remnant neck in both distally-placed stent cases but complete coverage in the proximally-placed stent cases. Thus, direct flow (impingement jet) removal from the aneurysm dome, as indicated by angiograms in the proximally-covered case, was sufficient to cause full aneurysm healing in four weeks; however, aneurysm healing was not complete for the distally-covered case. These results support further investigations into the treatment of aneurysms by flow-modification using partial aneurysm-orifice coverage.

  1. In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

    International Nuclear Information System (INIS)

    Nejjari, Mimoun; Kryza, David; Poncet, Gilles; Roche, Colette; Perek, Nathalie; Chayvialle, Jean-Alain; Le Bars, Didier; Scoazec, Jean-Yves; Janier, Marc; Borson-Chazot, Francoise

    2008-01-01

    Purpose: The aim of this study was to investigate (a) in vitro the relationship between [ 18 F]fluorocholine ([ 18 F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [ 18 F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [ 18 F]FCH and that of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) were measured before and after cytotoxic therapy. [ 18 F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [ 18 F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC 50 values calculated with the [ 18 F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [ 18 F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [ 18 F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [ 18 F]FCH in liver metastases but there was a significant uptake of [ 18 F]FDG. Conclusions: In vitro studies suggested that the incorporation of [ 18 F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [ 18 F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [ 18 F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded

  2. 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.

  3. Pharmacodynamics of beta-lactam antibiotics. Studies on the paradoxical and postantibiotic effects in vitro and in an animal model.

    Science.gov (United States)

    Odenholt-Tornqvist, I

    1989-01-01

    The pharmacodynamics of antibiotics, i.e. the rate of killing and the time before regrowth of surviving bacteria, may be important factors for determination of the dosage interval. In the present study the effect of protein binding, antibiotic concentrations, bacterial growth phase and bacterial inoculum on the rate of bacterial killing was investigated. The postantibiotic effect (PAE) was also studied in vitro and in vivo. The killing rate of S. aureus did not differ when the bacteria were exposed to the same free concentrations of dicloxacillin in medium with and without albumin. Protein binding per se did thus not diminish the bactericidal activity. A paradoxically reduced bactericidal effect was noted when S. aureus was exposed to high concentrations of dicloxacillin, cloxacillin and benzylpenicillin. For determination of PAE of imipenem on Ps. aeruginosa, counts of viable bacteria were compared with assay of bacterial intracellular ATP. Both methods demonstrated a PAE for the strains tested at an inoculum of 10(6) cfu/ml. At an inoculum of 10(8) cfu/ml no PAE was found, which coincided with a lack of bactericidal effect. Both the PAE and the bactericidal effect were restored with aeration of the cultures, indicating insufficient penetration of imipenem to the target sites at low oxygen tension. An in vivo model in rabbits with implanted tissue cages was developed for evaluation of the PAE. Group A beta-hemolytic streptococci showed a PAE of approximately 2 h in vivo, which correlated well with the PAE found in vitro. Despite that streptococci in postantibiotic phase (PA-phase) were non-multiplying, such bacteria were killed as efficiently as previously untreated controls when exposed to 10xMIC of penicillin both in vitro and in vivo. However, streptococci in PA-phase were much more sensitive to the repeated challenge to subinhibitory concentrations of penicillin than previously untreated controls. In vivo, no difference in sensitivity to sub-MIC penicillin

  4. 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

  5. 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.

  6. 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.

  7. Biological studies in animal models using [99mTc](CO)3 recombinant annexin V as diagnostic agent of apoptotic processes

    International Nuclear Information System (INIS)

    Teran, Mariella Adriana; Martinez, Elena; Reyes, Ana L.; Paolino, Andrea; Vital, Marcelo; Esperon, Patricia; Pacheco, Jose P.; Savio, Eduardo

    2011-01-01

    Introduction: There are many diseases associated with variations in the expression of apoptosis such as organ rejection after transplantation, myocardial ischemia or infarct and neurodegenerative diseases. For this reason, the early visualization of this process is relevant to set fast and effective therapeutic strategies. Methods: The precursor was prepared according to the procedure reported by R. Alberto, R. Schibli, P. Schubiger, U. Abram, and T. Kaden [Reactions with the technetium and rhenium carbonyl complexes (NEt 4 )[MX 3 (CO) 3 ]. Synthesis and structure of Tc(CN-But) 3 (CO) 3 ](NO 3 ) and (Net 4 )[Tc 2 (μ-SCH 2 CH 2 OH) 3 (CO) 3 ], Polyhedron 1996;15: 1079-89]. Recombinant annexin V was incubated with [ 99m Tc](H 2 O)3(CO) 3 + solution, previously neutralized with buffer. Biodistribution studies were performed in 8-week-old female Wistar rats. Animals were housed and treated in compliance with institutional guidelines related to animal experimentation. Work protocol was previously approved by the Animal Ethics Committee of the university. Two groups of rats were defined. One was used as control and the other group was previously injected with 150 mg/kg ip of cyclophosphamide to induce apoptosis. Results: The synthesis of carbonyl precursor achieved yields higher than 90%, and the radiolabeled protein was obtained with 92% of radiochemical purity and high stability in vitro. An important uptake in apoptotic tissues was confirmed by biodistributions, scintigraphic images and histological studies. Conclusions: Biodistribution studies revealed hepatobiliary elimination, high stability in vivo and important uptake in the reticuloendothelial system. In the pathologic model, higher uptake values correspond to the liver, spleen, lungs and femur. Histological studies confirmed the development of apoptosis at 8 and 24 h postinduction in the spleen and lymphocyte bulks in the peribronchial area. Scintigraphic images confirmed high uptake both the spleen and the

  8. 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

  9. Animal models of GM2 gangliosidosis: utility and limitations

    Science.gov (United States)

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

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

  10. SU-C-303-06: Treatment Planning Study for Non-Invasive Cardiac Arrhythmia Ablation with Scanned Carbon Ions in An Animal Model

    International Nuclear Information System (INIS)

    Eichhorn, A; Constantinescu, A; Prall, M; Kaderka, R; Durante, M; Graeff, C; Lehmann, H I; Takami, M; Packer, D L; Lugenbiel, P; Thomas, D; Richter, D; Bert, C

    2015-01-01

    Purpose: Scanned carbon ion beams might offer a non-invasive alternative treatment for cardiac arrhythmia, which are a major health-burden. We studied the feasibility of this procedure in an animal model. The underlying treatment planning and motion mitigation strategies will be presented. Methods: The study was carried out in 15 pigs, randomly distributed to 3 target groups: atrioventricular node (AVN, 8 animals with 25, 40, and 55 Gy target dose), left ventricular free-wall (LV, 4 animals with 40 Gy) and superior pulmonary vein (SPV, 3 animals with 40 Gy). Breathing motion was suppressed by repeated enforced breathholds at end exhale. Cardiac motion was mitigated by an inhomogeneous rescanning scheme with up to 15 rescans. The treatment planning was performed using the GSI in-house software TRiP4D on cardiac-gated 4DCTs, applying a range-considering ITV based on an extended CTV. For AVN and SPV isotropic 5 mm margins were applied to the CTV, while for the LV 2mm+2% range margins were used. The opposing fields for AVN and LV targets were optimized independently (SFUD), while SPV treatments were optimized as IMPT deliveries, including dose restrictions to the radiosensitive AVN. Results: Median value of D 95 over all rescanning simulations was 99.1% (AVN), 98.0% (SPV) and 98.3% (LV) for the CTV and 94.7% (AVN) and 92.7% (SPV) for the PTV, respectively. The median D 5 -D 95 was improved with rescanning compared to unmitigated delivery from 13.3 to 6.5% (CTV) and from 23.4 to 11.6% (PTV). ICRP dose limits for aorta, trachea, esophagus and skin were respected. The maximal dose in the coronary arteries was limited to 30 Gy. Conclusion: We demonstrated the feasibility of a homogeneous dose delivery to different cardiac structures in a porcine model using a time-optimized inhomogeneous rescanning scheme. The presented treatment planning strategies were applied in a pig study with the analysis ongoing. Funding: This work was supported in part by the Helmholtz Association

  11. SU-C-303-06: Treatment Planning Study for Non-Invasive Cardiac Arrhythmia Ablation with Scanned Carbon Ions in An Animal Model

    Energy Technology Data Exchange (ETDEWEB)

    Eichhorn, A; Constantinescu, A; Prall, M; Kaderka, R; Durante, M; Graeff, C [GSI Helmholtz Center, Darmstadt, DE (Germany); Lehmann, H I; Takami, M; Packer, D L [Mayo Clinic, Rochester, Minnesota (United States); Lugenbiel, P; Thomas, D [University of Heidelberg, Heidelberg, DE (Germany); Richter, D; Bert, C [University Clinic Erlangen, Erlagen, DE (Germany)

    2015-06-15

    Purpose: Scanned carbon ion beams might offer a non-invasive alternative treatment for cardiac arrhythmia, which are a major health-burden. We studied the feasibility of this procedure in an animal model. The underlying treatment planning and motion mitigation strategies will be presented. Methods: The study was carried out in 15 pigs, randomly distributed to 3 target groups: atrioventricular node (AVN, 8 animals with 25, 40, and 55 Gy target dose), left ventricular free-wall (LV, 4 animals with 40 Gy) and superior pulmonary vein (SPV, 3 animals with 40 Gy). Breathing motion was suppressed by repeated enforced breathholds at end exhale. Cardiac motion was mitigated by an inhomogeneous rescanning scheme with up to 15 rescans. The treatment planning was performed using the GSI in-house software TRiP4D on cardiac-gated 4DCTs, applying a range-considering ITV based on an extended CTV. For AVN and SPV isotropic 5 mm margins were applied to the CTV, while for the LV 2mm+2% range margins were used. The opposing fields for AVN and LV targets were optimized independently (SFUD), while SPV treatments were optimized as IMPT deliveries, including dose restrictions to the radiosensitive AVN. Results: Median value of D{sub 95} over all rescanning simulations was 99.1% (AVN), 98.0% (SPV) and 98.3% (LV) for the CTV and 94.7% (AVN) and 92.7% (SPV) for the PTV, respectively. The median D{sub 5}-D{sub 95} was improved with rescanning compared to unmitigated delivery from 13.3 to 6.5% (CTV) and from 23.4 to 11.6% (PTV). ICRP dose limits for aorta, trachea, esophagus and skin were respected. The maximal dose in the coronary arteries was limited to 30 Gy. Conclusion: We demonstrated the feasibility of a homogeneous dose delivery to different cardiac structures in a porcine model using a time-optimized inhomogeneous rescanning scheme. The presented treatment planning strategies were applied in a pig study with the analysis ongoing. Funding: This work was supported in part by the

  12. Application of system dynamics and participatory spatial group model building in animal health: A case study of East Coast Fever interventions in Lundazi and Monze districts of Zambia.

    Science.gov (United States)

    Mumba, Chisoni; Skjerve, Eystein; Rich, Magda; Rich, Karl M

    2017-01-01

    East Coast Fever (ECF) is the most economically important production disease among traditional beef cattle farmers in Zambia. Despite the disease control efforts by the government, donors, and farmers, ECF cases are increasing. Why does ECF oscillate over time? Can alternative approaches such as systems thinking contribute solutions to the complex ECF problem, avoid unintended consequences, and achieve sustainable results? To answer these research questions and inform the design and implementation of ECF interventions, we qualitatively investigated the influence of dynamic socio-economic, cultural, and ecological factors. We used system dynamics modelling to specify these dynamics qualitatively, and an innovative participatory framework called spatial group model building (SGMB). SGMB uses participatory geographical information system (GIS) concepts and techniques to capture the role of spatial phenomenon in the context of complex systems, allowing stakeholders to identify spatial phenomenon directly on physical maps and integrate such information in model development. Our SGMB process convened focus groups of beef value chain stakeholders in two distinct production systems. The focus groups helped to jointly construct a series of interrelated system dynamics models that described ECF in a broader systems context. Thus, a complementary objective of this study was to demonstrate the applicability of system dynamics modelling and SGMB in animal health. The SGMB process revealed policy leverage points in the beef cattle value chain that could be targeted to improve ECF control. For example, policies that develop sustainable and stable cattle markets and improve household income availability may have positive feedback effects on investment in animal health. The results obtained from a SGMB process also demonstrated that a "one-size-fits-all" approach may not be equally effective in policing ECF in different agro-ecological zones due to the complex interactions of socio

  13. Application of system dynamics and participatory spatial group model building in animal health: A case study of East Coast Fever interventions in Lundazi and Monze districts of Zambia.

    Directory of Open Access Journals (Sweden)

    Chisoni Mumba

    Full Text Available East Coast Fever (ECF is the most economically important production disease among traditional beef cattle farmers in Zambia. Despite the disease control efforts by the government, donors, and farmers, ECF cases are increasing. Why does ECF oscillate over time? Can alternative approaches such as systems thinking contribute solutions to the complex ECF problem, avoid unintended consequences, and achieve sustainable results? To answer these research questions and inform the design and implementation of ECF interventions, we qualitatively investigated the influence of dynamic socio-economic, cultural, and ecological factors. We used system dynamics modelling to specify these dynamics qualitatively, and an innovative participatory framework called spatial group model building (SGMB. SGMB uses participatory geographical information system (GIS concepts and techniques to capture the role of spatial phenomenon in the context of complex systems, allowing stakeholders to identify spatial phenomenon directly on physical maps and integrate such information in model development. Our SGMB process convened focus groups of beef value chain stakeholders in two distinct production systems. The focus groups helped to jointly construct a series of interrelated system dynamics models that described ECF in a broader systems context. Thus, a complementary objective of this study was to demonstrate the applicability of system dynamics modelling and SGMB in animal health. The SGMB process revealed policy leverage points in the beef cattle value chain that could be targeted to improve ECF control. For example, policies that develop sustainable and stable cattle markets and improve household income availability may have positive feedback effects on investment in animal health. The results obtained from a SGMB process also demonstrated that a "one-size-fits-all" approach may not be equally effective in policing ECF in different agro-ecological zones due to the complex

  14. Potential of Glutathione Antioxidant in the Hippocampus Repair: Preliminary Study on Bioactive Materials Antiaging of Snakehead Fish (Channa striata in Animal Models of Aging

    Directory of Open Access Journals (Sweden)

    Sunarno Sunarno

    2014-12-01

    Full Text Available Snakehead fish meat contains active ingredients with anti-aging potential that serves as a precursor of glutathione. The ability of glutathione as an antiaging opportunities in the utilization of fish meat, especially snakehead fish. Snakehead fish meat contains several important amino acids, such as glutamine, cysteine​​, and glycine so the potential to be developed for the production of food that is nutritious and healthy. This study examines the essential amino acid composition of the antioxidant glutathione precursors found in snakehead fish from Rawa Pening Central Java to increase glutathione in the body and brain. The results showed that every 100g of snakehead fish meat from Rawa Pening containing glutamine (32.39%, cysteine ​​(6.61%, and glycine (9.69%. Snakehead fish meat extract given at a dose of 30 ml/kg/day in both types of animal models of aging effect on the increase in the content of glutathione and glutathione precursors, both in blood and hippocampus. Increased glutathione precursor of the most high to low, respectively glutamine, glycine, and cysteine​​. Availability of essential amino acids can support increased glutathione in the brain. This is indicated by an increase in glutathione hippocampus in both animal models, both on chronological aging or aging due to oxidative stress, respectively (0.822 and 0.359 mol/g bb compared to control tissue.

  15. The HLA-B*5101 molecule-binding capacity to antigens used in animal models of Behçet's disease: a bioinformatics study.

    Science.gov (United States)

    Baharav, Ehud; Weinberger, Abraham

    2012-07-01

    The human lymphocyte antigen (HLA) molecule B*5101 is a functioning receptor of the immune system and is generally accepted as a genetic marker for Behçet disease (BD), a multi-organ, chronic inflammatory disorder. The role of the HLA-B*5101 in the pathogenesis of BD is elusive. The assumption that HLA-B*5101 has an active role in BD is suggestive, but no antigen has yet been identified. To evaluate the potential binding capacity of various antigens to the HLA-B*5101 molecule. Using bioinformatics programs, we studied the binding capacity of HLA-B*5101 and its corresponding rat molecule RT.A1 to the following antigens: heatshock protein-60 (HSP60), major histocompatibility complex class I chain-related gene A (MICA), retinal S-antigen (S-Ag), HLA-B27 molecule and its peptide (PD) and tropomyosin (TPM), all of which serve as antigens in animal models corresponding to BD. In each protein including the B*5101 molecule itself, the computerized programs revealed several short sequences with potential high binding capacity to HLA-B*5101 with the exception of B-27PD. The rat MHC RT1. Al. had no binding capacity to S-Ag. The evaluated proteins have the potential to bind to and to serve as potential antigens to the HLA-B*5101 and the rat MHC RT1.Al. molecules. The pathogenicity of these suggested short peptides should be evaluated in animal models of BD.

  16. Perinatal Hypoxia and Ischemia in Animal Models of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Dimitri Hefter

    2018-03-01

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

  17. 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.

  18. 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

  19. 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.

  20. Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

    Science.gov (United States)

    Bogachouk, Anna P; Storozheva, Zinaida I; Solovjeva, Olga A; Sherstnev, Vyacheslav V; Zolotarev, Yury A; Azev, Vyacheslav N; Rodionov, Igor L; Surina, Elena A; Lipkin, Valery M

    2016-01-01

    A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus. To evaluate cognitive functions in animals, three tests were used: the novel object recognition test, the conditioned passive avoidance task and the Morris maze. Comparative analysis of the data demonstrated that the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6-OH peptide. The greater cognitive/ behavioral effects can be attributed to improved kinetic properties of the amide form of the peptide, such as the character of biodegradation and the half-life time. The effects of HLDF-6-NH2 are comparable to, or exceed, those of the reference compounds. Importantly, HLDF-6-NH2 exerts its effects at much lower doses than the reference compounds. © The Author(s) 2015.

  1. Radionuclide therapy of skin cancers and Bowen's disease using specially designed skin patch: A pilot study in an animal model and clinical trial

    International Nuclear Information System (INIS)

    Lee, J. D.; Park, K. K.; Lee, M. G.; Lee, J. T.; Yoo, H. S.; Kim, E. H.; Rhim, K. J.; Kim, Y. M.; Park, K. B.; Kim, J. R.

    1997-01-01

    Skin cancer is the most common malignant tumors in human. Therapeutic modalities of the skin cancers are local destruction, radiotherapy and surgery. External radiation therapy leads to good results, however, overall 5-6 weeks of treatment period is needed to deliver optimal radiation dose to tumors. In this study, β-emitting radionuclide, Ho-166, impregnated in a specially designed patch was utilized to superficial skin cancers and Bowen's disease for local irradiation. Methods; Animal study was employed in 10 mice with chemically induced skin tumors. Five- mm size patches containing 22.2 -72.15 MBq(0.6 - 1.95 mCi) of Ho-166 were applied to the tumor surface for 1 -2 hr. In clinical trial, patients with squamous carcinoma(n=3), basal cell carcinoma(n=1), and Bowen's disease(n=1) were treated with patches containing 273.8 - 999 MBq (7.4 - 27 mCi) of Ho-166 for 30 minutes to 1 hour. Pathologic examination was performed 4 - 7 weeks after the treatment in animal model. Skin biopsy was performed 8 weeks post-treatment in four patients. Results; Tumor destruction was seen 1 week post the treatment, however, radiation dermatitis or ulceration developed at the site of radionuclide application. Those reactions healed gradually with fibrosis or epithelialization, which was confirmed pathologically. No significant adverse reaction to radiation except subcutaneous fibrosis was found. Conclusion; Superficial skin tumors could be successfully treated by topical application of β-emitting radionuclides. (author)

  2. 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.

  3. 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

  4. A study in male and female 5-HT transporter knockout rats : An animal model for anxiety and depression disorders

    NARCIS (Netherlands)

    Olivier, J D A; Van Der Hart, M G C; Van Swelm, R P L; Dederen, P J; Homberg, J R; Cremers, T; Deen, P M T; Cuppen, E; Cools, A R; Ellenbroek, B A

    2008-01-01

    Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat

  5. Randomized Crossover Study of Training Benefits of High Fidelity ECMO Simulation versus Porcine Animal Model An Interim Report

    Science.gov (United States)

    2017-02-25

    59 MDW/SGVU SUBJECT: Professional Presentation Approval 24 FEB 2017 1. Your paper, entitled Randomized C rossover Study of T raining Benefits of...have been the gold -standard for ECMO training due to their ability to replicate complex physiology and anatomic variation . Recently ECMO simulation

  6. A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders.

    NARCIS (Netherlands)

    Olivier, J.; Van Der Hart, M.G.C.; Van Swelm, R.P.L.; Dederen, P.J.; Homberg, J.R.; Cremers, T.; Deen, P.M.T.; Cuppen, E.; Cools, A.R.; Ellenbroek, B.A.

    2008-01-01

    Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat

  7. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

    Directory of Open Access Journals (Sweden)

    Caselli Chiara

    2012-11-01

    Full Text Available Abstract Background The role of systemic and myocardial adiponectin (ADN in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV free wall (180 beats/min, 3 weeks, both from pacing (PS and opposite sites (OS, and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

  8. 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

  9. In vivo animal studies with sugammadex.

    NARCIS (Netherlands)

    Booij, L.H.D.J.; Egmond, J. van; Driessen, J.J.; Boer, H.D. de

    2009-01-01

    A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of

  10. Phytochemical screening and studies of analgesic potential of Moringa oleifera Lam. stem bark extract on experimental animal model

    OpenAIRE

    Shumaia Parvin; Md. Abu Shuaib Rafshanjani; Md. Abdul Kader; Most. Afia Akhtar; Tahmida Sharmin

    2014-01-01

    The work has been done for the phytochemical investigation and study of analgesic activity of Moringa oleifera Lam. ethanolic stem bark extract using Acetic Acid Induced Writhing method. The effect of extract was tested for qualitative chemical analysis which reveals the presence of alkaloid, glycosides, flavonoids, tannins, saponin, carbohydrate etc. For peripheral analgesic effect acetic acid induced writhing test was used and for this stem bark extract was administered intraperitoneally at...

  11. Physiologic Responses to Infrarenal Aortic Cross-Clamping during Laparoscopic or Conventional Vascular Surgery in Experimental Animal Model: Comparative Study

    Directory of Open Access Journals (Sweden)

    María F. Martín-Cancho

    2008-01-01

    Full Text Available The aim of this study was to compare the hemodynamic and ventilatory effects of prolonged infrarenal aortic cross-clamping in pigs undergoing either laparotomy or laparoscopy. 18 pigs were used for this study. Infrarenal aortic crossclamping was performed for 60 minutes in groups I (laparotomy, n=6 and II (laparoscopy, n=6. Group III (laparoscopy, n=6 underwent a 120-minute long pneumoperitoneum in absence of aortic clamping (sham group. Ventilatory and hemodynamic parameters and renal function were serially determined in all groups. A significant decrease in pH and significant increase in PaCO2 were observed in group II, whereas no changes in these parameters were seen in group I and III. All variables returned to values similar to baseline in groups I and II 60 minutes after declamping. A significant increase in renal resistive index was evidenced during laparoscopy, with significantly higher values seen in Group II. Thus a synergic effect of pneumoperitoneum and aortic cross-clamping was seen in this study. These two factors together cause decreased renal perfusion and acidosis, thus negatively affecting the patient's general state during this type of surgery.

  12. Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients.

    Science.gov (United States)

    Hultborn, Hans

    2003-05-01

    It is a well-known fact that spinal reflexes may gradually change and often become enhanced following spinal cord lesions. Although these phenomena are known, the underlying mechanisms are still unknown and under investigation, mainly in animal models. Over the last twenty years, new methods have been developed that can reliably estimate the activity of specific spinal pathways in humans at rest and during voluntary movement. These methods now make it possible to describe components of the spinal pathophysiology in spasticity in humans following spinal lesions or stroke. We now know that spinal networks are capable of generating the basic pattern of locomotion in a large number of vertebrates, including the monkey--and in all likelihood, humans. Although spinal networks are capable of generating locomotor-like activity in the absence of afferent signals, functional gait is not possible without sensory feedback. The results of animal studies on the sensory control of and the transmitter systems involved in the spinal locomotor centers are now being used to improve rehabilitation of walking in persons with spinal cord injury and hemiplegia.

  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. Catheter-directed Intraportal Delivery of Endothelial Cell Therapy for Liver Regeneration: A Feasibility Study in a Large-Animal Model of Cirrhosis.

    Science.gov (United States)

    Lee, Kyungmouk Steve; Santagostino, Sara F; Li, David; Ramjit, Amit; Serrano, Kenneth; Ginsberg, Michael D; Ding, Bi-Sen; Rafii, Shahin; Madoff, David C

    2017-10-01

    Purpose To demonstrate the feasibility of imaging-guided catheter-directed delivery of endothelial cell therapy in a porcine model of cirrhosis for liver regeneration. Materials and Methods After approval from the institutional animal care and use committee, autologous liver endothelial cells were grown from core hepatic specimens from swine. Cirrhosis was induced in swine by means of transcatheter infusion of ethanol and iodized oil into the hepatic artery. Three weeks after induction of cirrhosis, the swine were randomly assigned to receive autologous cell therapy (endothelial cells, n = 4) or control treatment (phosphate-buffered saline, n = 4) by means of imaging-guided transhepatic intraportal catheterization. Fluorescence-activated cell sorting analysis was performed on biopsy samples 1 hour after therapy. Three weeks after intraportal delivery of endothelial cells, the swine were euthanized and the explanted liver underwent quantitative pathologic examination. Statistical analysis was performed with an unpaired t test by using unequal variance. Results Liver endothelial cells were successfully isolated, cultured, and expanded from eight 20-mm, 18-gauge hepatic core samples to 50 × 10 6 autologous cells per pig. Intraportal delivery of endothelial cell therapy or saline was technically successful in all eight swine, with no complications. Endothelial cells were present in the liver for a minimum of 1 hour after intraportal infusion. Swine treated with endothelial cell therapy showed mean levels of surrogate markers of hepatobiliary injury that were consistent with decreases in hepatic fibrosis and biliary ductal damage relative to the control animals, although statistical significance was not met in this pilot study: The mean percentage of positive pixels at Masson trichrome staining was 7.28% vs 5.57%, respectively (P = .20), the mean proliferation index with cytokeratin wide-spectrum was 2.55 vs 1.13 (P = .06), and the mean proliferation index with Ki67

  15. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    Science.gov (United States)

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo; López-Alcorocho, Juan Manuel

    2014-04-01

    We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.

  16. Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

    Full Text Available BACKGROUND/AIM: Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. METHODS/RESULTS: Male C57BL/6 mice were fed with a standardized high-fat diet (obese or regular diet (normal for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method and by hemodynamic parameters (invasive method. Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction, and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. CONCLUSIONS: Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  18. 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. Biological studies in animal models using [{sup 99m}Tc](CO){sub 3} recombinant annexin V as diagnostic agent of apoptotic processes

    Energy Technology Data Exchange (ETDEWEB)

    Teran, Mariella Adriana, E-mail: mteran@fq.edu.u [Catedra de Radioquimica, Departamento Estrella Campos, Facultad de Quimica, Universidad de la Republica, P.O. 11800, Montevideo (Uruguay); Martinez, Elena; Reyes, Ana L.; Paolino, Andrea [Catedra de Radioquimica, Departamento Estrella Campos, Facultad de Quimica, Universidad de la Republica, P.O. 11800, Montevideo (Uruguay); Vital, Marcelo; Esperon, Patricia [Catedra de Biologia Molecular, Departamento de Bioquimica Clinica, Facultad de Quimica, Universidad de la Republica, Montevideo (Uruguay); Pacheco, Jose P. [Instituto de Patobiologia, Facultad de Veterinaria, Universidad de la Republica, Montevideo (Uruguay); Savio, Eduardo [Catedra de Radioquimica, Departamento Estrella Campos, Facultad de Quimica, Universidad de la Republica, P.O. 11800, Montevideo (Uruguay)

    2011-02-15

    Introduction: There are many diseases associated with variations in the expression of apoptosis such as organ rejection after transplantation, myocardial ischemia or infarct and neurodegenerative diseases. For this reason, the early visualization of this process is relevant to set fast and effective therapeutic strategies. Methods: The precursor was prepared according to the procedure reported by R. Alberto, R. Schibli, P. Schubiger, U. Abram, and T. Kaden [Reactions with the technetium and rhenium carbonyl complexes (NEt{sub 4})[MX{sub 3}(CO){sub 3}]. Synthesis and structure of Tc(CN-But){sub 3}(CO){sub 3}](NO{sub 3}) and (Net{sub 4})[Tc{sub 2}({mu}-SCH{sub 2}CH{sub 2}OH){sub 3}(CO){sub 3}], Polyhedron 1996;15: 1079-89]. Recombinant annexin V was incubated with [{sup 99m}Tc](H{sub 2}O)3(CO){sub 3}{sup +} solution, previously neutralized with buffer. Biodistribution studies were performed in 8-week-old female Wistar rats. Animals were housed and treated in compliance with institutional guidelines related to animal experimentation. Work protocol was previously approved by the Animal Ethics Committee of the university. Two groups of rats were defined. One was used as control and the other group was previously injected with 150 mg/kg ip of cyclophosphamide to induce apoptosis. Results: The synthesis of carbonyl precursor achieved yields higher than 90%, and the radiolabeled protein was obtained with 92% of radiochemical purity and high stability in vitro. An important uptake in apoptotic tissues was confirmed by biodistributions, scintigraphic images and histological studies. Conclusions: Biodistribution studies revealed hepatobiliary elimination, high stability in vivo and important uptake in the reticuloendothelial system. In the pathologic model, higher uptake values correspond to the liver, spleen, lungs and femur. Histological studies confirmed the development of apoptosis at 8 and 24 h postinduction in the spleen and lymphocyte bulks in the peribronchial area

  20. 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.

  1. A comparison of generalized multinomial logit, random parameters logit, wtp-space and latent class models to studying consumers' preferences for animal welfare

    OpenAIRE

    Kallas, Zein; Borrisser-Pairó,, Francesc; Martínez, Beatriz; Vieira, Ceferina; Panella-Riera, Nuria; Olivar, Maria Angels; Gil Roig, José María

    2016-01-01

    The European societies are requiring that animals to be raised as closely as possible to their natural conditions. The growing concerns about animal welfare is resulting in continuous modifications of regulations and policies that led to ban of a number of intensive farming methods. The European authorities consider the pig welfare as a priority issue. They are studying to ban surgical pig castration by 2018, which may seriously affect markets and consumers due to boar tainted-meat. This stud...

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. Animal studies on growth and development.

    Science.gov (United States)

    Lerchl, Alexander

    2011-12-01

    Despite the fact that no plausible biological mechanism has yet been identified how electromagnetic fields below recommended exposure limits could negatively affect health of animals or humans, many experiments have been performed in various animal species, mainly mice and rats, to investigate the possible effects on growth and development. While older studies often suffered from sub-optimal exposure conditions, recent investigations, using sophisticated exposure devices and thus preventing thermal effects, have been performed without these limitations. In principle, two types of studies can be addressed: those which have investigated the carcinogenic or co-carcinogenic effects of exposure in developing animals, and those which have been done in developing animals without the focus on carcinogenic or co-carcinogenic effects. In both areas, the vast majority of publications did not show adverse effects. The largest study so far has been done in normal mice which have been chronically exposed to UMTS signals up to 1.3 W/kg SAR, thus 16 times higher than the whole-body exposure limit for humans. Even after four generations, no systematic or dose-dependent alterations in development or fertility could be found, supporting the view that negative effects on humans are very unlikely. Ongoing experiments in our laboratory investigate the effects of head-only exposure in rats (up to 10 W/kg local SAR) which are exposed from 14 days of age daily for 2 h. A battery of behavioral tests is performed in young, adult, and pre-senile animals. The results will help to clarify possible effects of exposure on brain development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Fundamental study on nuclear medicine imaging of cholinergic innervation in the brain; Changes of neurotransmitter and receptor in animal model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi; Kinuya, Keiko; Sumiya, Hisashi; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine; Tsuji, Shiro; Terada, Hitoshi; Shiba, Kazuhiro; Mori, Hirofumi

    1990-10-01

    A fundamental study was performed on the nuclear medicine imaging of cholinergic innervation in the brain. In a cholinergic denervation model prepared by producing an unilateral basal forebrain lesion in the rat, which is reported to be one of animal models of Alzheimer' disease, quantitative determination of acetylcholine in parietal cortices revealed statistically significant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In vitro receptor autoradiography showed no significant differences in total, M{sub 1}, and M{sub 2} muscarinic acetylcholine receptors between the ipsilateral and contralateral cortices to the lesion. Simultaneous mapping of presynaptic cholinergic innervation using {sup 3}H-2-(4-phenylpiperidino) cyclohexanol (AH5183) demonstrated significant 14% decrease of AH5183 binding on an average in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promising ligand for mapping cholinergic innervation in nuclear medicine imaging. (author).

  13. Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

    Science.gov (United States)

    Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

    2015-07-14

    Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Study of inhaled radio-active pollutants: 1. Current data; II. Pathology; III. Validity of animal model. Dose-effect relations

    International Nuclear Information System (INIS)

    Lafuma, J.; Masse, R.; Metivier, H.; Nolibe, D.; Fritsch, P.; Nenot, J.C.; Morin, M.

    1974-01-01

    An attempt has been made to develop an animal for human industrial exposure to airradiation. That will give results applicable to man both qualitatively and quantitavely. Using over 2000 animals. The following studies were made. Radon, rat and occupationally exposed man; 239 plutonium oxide, rat and monkey; 12 different α and emitters, rat with different exposure media (aerosols particles) and exposure shcedules (acute chronic). Scrupulous pathological, microscopic, autoradiographic and ultrastructural analysis of animals followed their deaths. Acute changes are characterized by alveolaroedema, capillary and arteriolar thrombisus, and desquamation of type 1 pneumatocytes. There is interstitial pneumonia, hyaline membrane formation, and extensive bronchiolar and alveolar metaplasia. In a study of long-term effects a wide variety of both benign and malignant tumours was discovered. There are variations in species lateney and radiation sensitivity. The pathological changes, found in these studies are qualitatively very similar to changes found in man [fr

  15. 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

  16. The Modulatory Properties of Chronic Antidepressant Drugs Treatment on the Brain Chemokine – Chemokine Receptor Network: A Molecular Study in an Animal Model of Depression

    Directory of Open Access Journals (Sweden)

    Ewa Trojan

    2017-11-01

    Full Text Available An increasing number of studies indicate that the chemokine system may be the third major communication system of the brain. Therefore, the role of the chemokine system in the development of brain disorders, including depression, has been recently proposed. However, little is known about the impact of the administration of various antidepressant drugs on the brain chemokine – chemokine receptor axis. In the present study, we used an animal model of depression based on the prenatal stress procedure. We determined whether chronic treatment with tianeptine, venlafaxine, or fluoxetine influenced the evoked by prenatal stress procedure changes in the mRNA and protein levels of the homeostatic chemokines, CXCL12 (SDF-1α, CX3CL1 (fractalkine and their receptors, in the hippocampus and frontal cortex. Moreover, the impact of mentioned antidepressants on the TGF-β, a molecular pathway related to fractalkine receptor (CX3CR1, was explored. We found that prenatal stress caused anxiety and depressive-like disturbances in adult offspring rats, which were normalized by chronic antidepressant treatment. Furthermore, we showed the stress-evoked CXCL12 upregulation while CXCR4 downregulation in hippocampus and frontal cortex. CXCR7 expression was enhanced in frontal cortex but not hippocampus. Furthermore, the levels of CX3CL1 and CX3CR1 were diminished by prenatal stress in the both examined brain areas. The mentioned changes were normalized with various potency by chronic administration of tested antidepressants. All drugs in hippocampus, while tianeptine and venlafaxine in frontal cortex normalized the CXCL12 level in prenatally stressed offspring. Moreover, in hippocampus only fluoxetine enhanced CXCR4 level, while fluoxetine and tianeptine diminished CXCR7 level in frontal cortex. Additionally, the diminished by prenatal stress levels of CX3CL1 and CX3CR1 in the both examined brain areas were normalized by chronic tianeptine and partially fluoxetine

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Why do we study animal toxins?

    Science.gov (United States)

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  3. Evaluation of nigrostriatal damage and its change over weeks in a rat model of Parkinson's disease: small animal positron emission tomography studies with [11C]β-CFT

    International Nuclear Information System (INIS)

    Liu Limin; Wang Yong; Li Bo; Jia Jun; Sun Zuoli; Zhang Jinming; Tian Jiahe; Wang Xiaomin

    2009-01-01

    Introduction: The cardinal pathological feature of Parkinson's disease (PD) is progressive loss of dopaminergic neurons. Since dopamine transporter (DAT) is a protein located presynaptically on dopaminergic nerve terminals, radioligands that bind to these sites are promising radiopharmaceuticals for evaluation of the integrity of the dopamine system. This study using positron emission tomography (PET) tracers, [ 11 C]-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane ([ 11 C]β-CFT, radioligand for DAT), was aimed at evaluating the degree of nigrostriatal damage and its change over weeks in a rat model of PD. Methods: The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the medial forebrain bundle (MFB). Behavioral studies were carried out by apomorphine (APO) challenge prior to and 1, 2 and 4 weeks after MFB axotomy. Small animal PET scans were performed 2 days after the behavioral test. Immunohistochemistry was conducted 4 days after the last PET scan. Results: Compared with the contralateral intact side, a progressively decreased [ 11 C]β-CFT binding was observed on the lesioned side which correlated inversely with the APO-induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. Conclusion: These findings not only demonstrate that the neuronal degeneration in this model is relatively slow, but also suggest [ 11 C]β-CFT is a sensitive marker to monitor the degree of nigrostriatal damage and its change over weeks. This marker can be used prospectively to study the progression of the disease, thereby making detection of early phases of PD possible.

  4. 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

  5. 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

  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. 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.

  8. Comparative study of two boron compounds (BPA and BOPP) for the application of BNCT to an animal model of undifferentiated thyroid cancer

    International Nuclear Information System (INIS)

    Dagrosa, Maria A.; Viaggi, Mabel; Juvenal, Guillermo; Pisarev, Mario A.

    2003-01-01

    Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron compounds by tumors. Once the uptake, relative to normal tissues, is equal of greater than 3, the tumoral area is irradiated with an appropriate neutron beam. The 10 B is then converted into 11 B and this decays releasing an atom of Li, gamma rays and alpha particles. These latter have a high linear energy transfer (LET) and will cause local damage, eventually killing the tumoral cells. At the present time several clinical trials are being conducted in different countries to treat patients with glioblastoma multiform and melanomas. So far the results obtained, specially with this last disease, are quite encouraging. Undifferentiated thyroid cancer (UTC) is a very aggressive tumor which does not respond to the therapies available at the present. Usually it has a very bad prognosis with a very short survival period. We have previously shown that the human UTC cell line ARO has an uptake of borophenylanine (BPA) significantly greater than normal thyroid or than human follicular adenoma cells in culture. Moreover, an animal model for UTC was developed in our laboratory by transplanting the human ARO cells into nude mice. This model closely resembles the evolution of human disease and even produces lung metastasis, like the human. In the present studies we have compared the uptake of two boron compounds: BPA and boronated porphyrin (BOPP). BPA was administered via ip in a dose of 600 mg/kg body weight, while BOPP was given either ip or iv, in doses of 10 and 100 mg/kg body weight. The animals were sacrificed at different times after the injection: up to 150 min for BPA and after 24 h with BOPP. The concentration of boron was determined by ICP-AES. The results obtained showed that the uptake of BPA was significantly greater in the tumoral area and in the infiltrated surrounding skin than in the other organs examined (liver, kidney, lung, mice thyroid, blood, spleen and distal skin

  9. 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

  10. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

    Directory of Open Access Journals (Sweden)

    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Animation of 3D Model of Human Head

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    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.

  16. 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.

  17. 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.

  18. A controlled study to investigate anti-diarrhoeal effect of the stem-bark fractions of Terminalia avicennioides in laboratory animal models

    Directory of Open Access Journals (Sweden)

    Mohammed M. Suleiman

    2017-06-01

    Full Text Available Due to the shortcomings associated with modern synthetic antidiarrhoeal drugs, it is important to find newer, safer and cheaper antidiarrhoeal agents from natural sources. The study was conducted to evaluate the anti-diarrhoeal activity of the fractions of the stem-bark of Terminalia avicennioides in laboratory animal models. The effect of different concentrations (1.0 × 10−3, 2.0 × 10−3, 4.0 × 10−3 and 8.0 × 10−3 mg/mL of the aqueous methanol (AMF, ethyl acetate (EAF and hexane (HXF fractions of T. avicennioides were tested against spontaneous and acetylcholine-induced contractions of rabbit jejunum as well as on histamine-induced contraction of guinea pig ileum. Similarly, the effects of the AMF on gastro-intestinal transit time, castor oil-induced diarrhoea and castor oil-induced enteropooling were evaluated. The AMF, EAF and HXF at concentrations of 1.0 × 10−3, 2.0 × 10−3, 4.0 × 10−3 and 8.0 × 10−3 mg/mL attenuated the contractile effects of both the spontaneous and acetylcholine-induced contractions of rabbit jejunum and that of histamine-induced contraction of guinea pig ileum in a concentration-dependent manner. The AMF at doses of 200, 300 and 500 mg/kg produced significant (p < 0.05 reductions in gastrointestinal transit time of charcoal and incidence of castor oil-induced diarrhoea in mice relative to the untreated control. Similarly, at doses of 300 and 500 mg/kg, AMF significantly (p < 0.05 reduced the weight and volume of intestinal fluid in the treated mice when compared to the untreated animals. The results of this study showed that the stem-bark of T. avicennioides possesses spasmolytic effect and could be a potential antidiarrhoeal agent. However, detailed pharmacological trials are required to justify the clinical use of the plant for treating diarrhoea.

  19. Estudo sobre a eficácia da aerostasia pulmonar, em modelo animal, utilizando diferentes tipos de suturas Study about the ability of the pulmonary aerostasia, in animal model, using differents parenchymal pulmonary types of the sutures

    Directory of Open Access Journals (Sweden)

    Darcy Ribeiro Pinto Filho

    2003-10-01

    Full Text Available INTRODUÇÃO: A busca de um modelo perfeito de aerostasia pulmonar, após cirurgias que envolvam ressecções parciais, permanece um desafio para a prática da cirurgia torácica. OBJETIVO: Avaliar e comparar, em um modelo animal (suínos, a eficácia de quatro diferentes tipos de sutura pulmonar em manter aerostasia. MÉTODO: Estudo experimental, ex vivo, em pulmões de suínos, realizado no biotério da Universidade de Caxias do Sul. Quatro tipos de sutura pulmonares foram avaliadas: tipo 1, sutura manual com fios cirúrgicos absorvíveis; tipo 2, grampeador exclusivo; tipo 3, grampeador recoberto por pericárdio bovino e tipo 4, grampeador recoberto por cola biológica. As suturas foram submetidas a níveis crescentes de pressão, que variaram de 10cmH2O a 60cmH2O. O teste do borracheiro avaliou o hermetismo das suturas. RESULTADOS: A média de pressão em que se observou perda do hermetismo pulmonar foi de 29cmH2O no tipo 1 (n = 10; 38,5cmH2O no tipo 2 (n = 10; 44cmH2O no tipo 3 (n = 10 e 51,4cmH2O no tipo 4 (n = 10. A comparação entre as médias mostrou diferença estatística apenas entre as suturas tipo 1 e as suturas tipo 3 e 4, p = 0,04 e p BACKGROUND: The search for an ideal procedure to accomplish aerostasis, after partial surgical resection of the lung parenchyma, remains a practical challenge for the thoracic surgeon. OBJECTIVE: The objective of this study was to compare the ability of four types of parenchymal pulmonary sutures in preventing air leaks, using a porcine model with incremental endobronchial pressures. METHOD: Ex vivo experimental study in porcine lungs (n = 5 at the Laboratory of Experimental Surgery of the Universidade de Caxias do Sul. Four different parenchymal pulmonary types of suture were analyzed: type 1 (absorbable suture, type 2: (stapled suture, type 3 (stapled suture with bovine pericardium and type 4 (stapled suture with biologic glue. The surgical sutures (n = 40 were exposed to different intrabronchial

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

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    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

  7. 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.

  8. 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)

  9. 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)

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

    Science.gov (United States)

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

    2011-01-01

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

  11. 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.

  12. 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

  13. Development of biomarker specific of pancreatic beta cells (incretin radiolabelled) for image of beta functional mass in diabetic and obese: study in animal model

    International Nuclear Information System (INIS)

    Seo, Daniele

    2017-01-01

    Increased prevalence of obesity worldwide, has become a vast concern, stimulating investigations focusing prevention and therapy of this condition. The association of type 2 diabetes or insulin resistance aggravates the prognosis of obesity. Even patients successfully submitted to bariatric or metabolic surgery, may not be cured of diabetes, as improvement of circulating values of glucose and insulin not necessarily reflects recovery of pancreatic beta cell mass. There is no consensus about how to estimate beta cell mass in vivo. Available tools suffer from low sensitivity and specificity, often being as well cumbersome and expensive. Radiolabeled incretins, such as glucagon-like-peptide 1 (GLP-1) analogs, seem to be promising options for the measurement of beta cell mass in diabetes and insulinoma. The objective of this study was the development of two conjugates of GLP-1 analog, radiolabeled with 99m Technetium, as a noninvasive imaging method for the estimation of pancreatic beta cell mass, in the presence of obesity. Animal models were selected, including hyperlipidic diet-induced obesity, diet restricted obesity, and as controls, alloxan diabetes. Results indicated that both radiotracers achieved over 97% radiochemical yield. The most successful product was 99m Tc-HYNIC-βAla-Exendin-4. Low beta cell mass uptake occurred in diet-induced obesity. Diet-restricted obesity, with substantial shedding of excess body weight, was followed by remarkable decrease of fasting blood glucose, however beta cell mass uptake was only mildly improved. Future studies are recommended in obesity, type 2 diabetes, and dieting, including bariatric and metabolic operations. (author)

  14. 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

  15. 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.

  16. 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.

  17. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    International Nuclear Information System (INIS)

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S.

    1990-01-01

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions

  18. 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

  19. 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.

  20. 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…

  1. 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.)

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. Strategies for improving the Voxel-based statistical analysis for animal PET studies: assessment of cerebral glucose metabolism in cat deafness model

    International Nuclear Information System (INIS)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Kang, Hye Jin; Im, Ki Chun; Moon, Dae Hyuk; Lim, Sang Moo; Oh, Seung Ha; Lee, Dong Soo

    2007-01-01

    In imaging studies of the human brain, voxel-based statistical analysis method was widely used, since these methods were originally developed for the analysis of the human brain data, they are not optimal for the animal brain data. The aim of this study is to optimize the procedures for the 3D voxel-based statistical analysis of cat FDG PET brain images. A microPET Focus 120 scanner was used. Eight cats underwent FDG PET scans twice before and after inducing the deafness. Only the brain and adjacent regions were extracted from each data set by manual masking. Individual PET image at normal and deaf state was realigned to each other to remove the confounding effects by the different spatial normalization parameters on the results of statistical analyses. Distance between the sampling points on the reference image and kernel size of Gaussian filter applied to the images before estimating the realignment parameters were adjusted to 0.5 mm and 2 mm. Both data was then spatial normalized onto study-specific cat brain template. Spatially normalized PET data were smoothed and voxel-based paired t-test was performed. Cerebral glucose metabolism decreased significantly after the loss of hearing capability in parietal lobes, postcentral gyri, STG, MTG, lTG, and IC at both hemisphere and left SC (FDR corrected P < 0.05, k=50). Cerebral glucose metabolism in deaf cats was found to be significantly higher than in controls in the right cingulate (FDR corrected P < 0.05, k=50). The ROI analysis also showed significant reduction of glucose metabolism in the same areas as in the SPM analysis, except for some regions (P < 0.05). Method for the voxel-based analysis of cat brain PET data was optimized for analysis of cat brain PET. This result was also confirmed by ROI analysis. The results obtained demonstrated the high localization accuracy and specificity of the developed method, and were found to be useful for examining cerebral glucose metabolism in a cat cortical deafness model

  8. Strategies for improving the Voxel-based statistical analysis for animal PET studies: assessment of cerebral glucose metabolism in cat deafness model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Kang, Hye Jin; Im, Ki Chun; Moon, Dae Hyuk; Lim, Sang Moo; Oh, Seung Ha; Lee, Dong Soo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In imaging studies of the human brain, voxel-based statistical analysis method was widely used, since these methods were originally developed for the analysis of the human brain data, they are not optimal for the animal brain data. The aim of this study is to optimize the procedures for the 3D voxel-based statistical analysis of cat FDG PET brain images. A microPET Focus 120 scanner was used. Eight cats underwent FDG PET scans twice before and after inducing the deafness. Only the brain and adjacent regions were extracted from each data set by manual masking. Individual PET image at normal and deaf state was realigned to each other to remove the confounding effects by the different spatial normalization parameters on the results of statistical analyses. Distance between the sampling points on the reference image and kernel size of Gaussian filter applied to the images before estimating the realignment parameters were adjusted to 0.5 mm and 2 mm. Both data was then spatial normalized onto study-specific cat brain template. Spatially normalized PET data were smoothed and voxel-based paired t-test was performed. Cerebral glucose metabolism decreased significantly after the loss of hearing capability in parietal lobes, postcentral gyri, STG, MTG, lTG, and IC at both hemisphere and left SC (FDR corrected P < 0.05, k=50). Cerebral glucose metabolism in deaf cats was found to be significantly higher than in controls in the right cingulate (FDR corrected P < 0.05, k=50). The ROI analysis also showed significant reduction of glucose metabolism in the same areas as in the SPM analysis, except for some regions (P < 0.05). Method for the voxel-based analysis of cat brain PET data was optimized for analysis of cat brain PET. This result was also confirmed by ROI analysis. The results obtained demonstrated the high localization accuracy and specificity of the developed method, and were found to be useful for examining cerebral glucose metabolism in a cat cortical deafness model.

  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. [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.

  11. 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.

  12. Experimental animal studies of radon and cigarette smoke

    International Nuclear Information System (INIS)

    Cross, F.T.; Dagle, G.E.; Gies, R.A.; Smith, L.G.; Buschbom, R.L.

    1992-01-01

    Cigarette-smoking is a dominant cause of lung cancer and confounds risk assessment of exposure to radon decay products. Evidence in humans on the interaction between cigarette-smoking and exposure to radon decay products, although limited, indicates a possible synergy. Experimental animal data, in addition to showing synergy, also show a decrease or no change in risk with added cigarette-smoke exposures. This article reviews previous animal data developed at Compagnie Generale des Matieres Nucleaires and Pacific Northwest Laboratory (PNL) on mixed exposures to radon and cigarette smoke, and highlights new initiation-promotion-initiation (IPI) studies at PNL that were designed within the framework of a two-mutation carcinogenesis model. Also presented are the PNL exposure system, experimental protocols, dosimetry, and biological data observed to date in IPI animals

  13. 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

  14. 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?

  15. 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.

  16. Right atrium and superior vena cava pressure measurements in a novel animal model to study one and a half ventricle repair as compared to Fontan type procedure

    Directory of Open Access Journals (Sweden)

    Anil Bhattarai

    2017-01-01

    Full Text Available Background & Objectives: To evaluate the advantages of the one and a half ventricle repair on maintaining a low pressure in the inferior vena cava district. Also evaluate the competition of flows at the superior vena cava – right pulmonary artery anastomosis site, in order to understand the hemodynamic interaction of a pulsatile flow in combination to a laminar one. Materials & Methods: Adult rabbits (n=30 in terminal anaesthesia with a follow up of 8 h were used, randomly distributed in three experimental groups: Group 1: animals with an anastomosis between superior vena cava and right pulmonary artery, as a model of one and one half ventricle repair; Group 2: animals with the cavopulmonary anastomosis followed by clamping of the right pulmonary artery proximal to the anastomosis; and Group 3: sham animals. Pressures of superior vena cava and pulmonary arteries were afterwards measured, in a resting condition as well as after induced pharmacological stress test.Results: In Group 1, superior vena cava pressure was significantly higher, while venous pressure in the inferior vena cava – right atrium district was constant or lower in comparison with the other groups. After stress test, the pressure in the superior vena cava and the heart rate both increased further, but the right ventricular, right atrial and pulmonary artery pressures remained similar to the values in a resting condition. This proved that the inferior vena cava return was well-preserved, and no venous hypertension was present in the inferior vena cava district even after stress test (good exercise tolerance.Conclusion: One and one half ventricle repair can be considered a good surgical strategy for maintaining a low pressure in the inferior vena cava district with potential for right ventricle growth, restoring the more physiological circulation in borderline or failing right ventricle conditions. The experiment presented a positive finding in favour of one and one half

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

    Science.gov (United States)

    Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

    2011-12-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  5. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

    2011-01-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  6. 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

  7. 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.

  8. Role of 188Re(V)DMSA in the diagnosis and therapy of medullary thyroid carcinoma: a pilot study in an animal model

    International Nuclear Information System (INIS)

    Learoyd, D.L.; Roach, P.J.; Snowdon, G.M.; Dadachova, K.; Moreau, A.M.; Robinson, B.G.

    1999-01-01

    Full text: 99 Tc m (V)DMSA has been reported to be highly sensitive in the diagnosis of medullary thyroid cancer (MTC). Rhenium-188, a beta emitter, has potential for therapy of MTC. However, initial studies with 188 Re indicate high renal uptake which may interfere with potential therapeutic applications of this radiopharmaceutical. A modified radiolabelling method has been shown to reduced the renal uptake of 188 Re(V)DMSA in control animals. The aims of this study were to determine whether there is uptake of modified 188 Re(V)DMSA in nude mice injected with an MTC cell line and whether there is potential for MTC therapy. Two groups of mice were injected in the left flank (SC) with TT cell line, and in mice showing tumour growth a low-dose (400 kBq) of 188 Re(V)DMSA was injected via a tail vein 8 weeks later. Biodistribution was performed on several mice and several others were given 'therapy' injections (8 MBq) to determine whether tumour shrinkage could be objectively observed. Tracer uptake was highest in bone and kidneys but tumour uptake was relatively low. However, no new tumour growth was seen in any of the mice subsequent to therapy injections and 1 mouse showed complete remission within 5 weeks of injection. Further animal and human studies will need to be performed to determine the potential role of this modified 118 Re(V)DMSA in patients with MTC

  9. 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.

  10. 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.

  11. 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;

  12. 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.

  13. 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.

  14. Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

    Science.gov (United States)

    Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

    2008-03-01

    The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

  15. 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…

  16. 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…

  17. 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.

  18. A new animal model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Andersen, Mads Varis Nis; Wiencke, Anne

    2005-01-01

    The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig.......The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig....

  19. Imaging of bioluminescent LNCaP-luc-M6 tumors: a new animal model for the study of metastatic human prostate cancer.

    Science.gov (United States)

    Scatena, Caroline D; Hepner, Mischa A; Oei, Yoko A; Dusich, Joan M; Yu, Shang-Fan; Purchio, Tony; Contag, Pamela R; Jenkins, Darlene E

    2004-05-15

    Animal experiments examining hormone-sensitive metastatic prostate cancer using the human LNCaP cell line have been limited to endpoint analyses. To permit longitudinal studies, we generated a luciferase-expressing cell line and used bioluminescent imaging (BLI) to non-invasively monitor the in vivo growth of primary LNCaP tumors and metastasis. LNCaP.FGC cells were transfected to constitutively express firefly luciferase. LNCaP-luc-M6 cells were tested for bioluminescent signal intensity and hormone responsiveness in vitro. The cells were implanted in subcutaneous and orthotopic sites in SCID-bg mice and imaged over time. The LNCaP-luc-M6 cells formed subcutaneous and orthotopic tumors in SCID-bg mice, and nearly all tumor-bearing animals developed pulmonary metastases. Early detection and temporal growth of primary tumors and metastatic lesions was successfully monitored by BLI. The LNCaP-luc-M6 cell line is a bioluminescent, hormone-sensitive prostate cancer cell line applicable for BLI studies to non-invasively monitor subcutaneous and orthotopic prostate tumor growth and metastasis in vivo. Copyright 2004 Wiley-Liss, Inc.

  20. 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.

  1. 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...

  2. 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

  3. [Tricholoma equestre--animal toxicity study].

    Science.gov (United States)

    Chodorowski, Zygmunt; Sznitowska, Małgorzata; Wiśniewski, Marek; Sein Anand, Jacek; Waldman, Wojciech; Ronikier, Anna

    2004-01-01

    Animal toxicity study of Tricholoma equestre mushrooms stored for 12 months at (-)20 degrees C was performed using 30 male BALB/c mice. Three groups of 5 mice each were given suspension of T. equestre powder in water, boiled aqueous extract and chloroform-methanol extract dissolved in Miglyol 812 by gavage for three consecutive days. Mice in control groups were given water, Miglyol 812 and p-phenylenediamine (CAS 106-50-3). Creatine kinase activity was determined in serum collected 72 hours after the final dose. Mean activity of serum creatine kinase in mice treated with T. equestre powder, aqueous extract, chloroform-methanol extract and Miglyol 812 were 157 +/- 93, 129 +/- 30, 96 +/- 38, 111 +/- 66 U/L respectively and did not differ significantly from mean activity in mice which were given water (107 +/- 38 U/L). Mean serum creatine kinase activity in p-phenylenediamine group (265 +/- 63 U/L) was significantly higher than in group treated with water (p<0.01). Extracts of Tricholoma equestre mushrooms stored for 12 months at (-)20 degrees C did not cause rhabdomyolysis in male BALB/c mice.

  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. Bladder pressure sensors in an animal model

    NARCIS (Netherlands)

    Koldewijn, E. L.; van Kerrebroeck, P. E.; Schaafsma, E.; Wijkstra, H.; Debruyne, F. M.; Brindley, G. S.

    1994-01-01

    Urinary incontinence due to detrusor hyperreflexia might be inhibited on demand if changes in bladder pressure could be detected by sensors and transferred into pudendal nerve electrostimulation. The aim of this study is to investigate how the bladder wall reacts on different sensor implants.

  6. Biodistribution of Carbon Nanotubes in Animal Models

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter Horn; Clausen, Per Axel

    2017-01-01

    the main sites of long-term CNT accumulation, which also includes pleura, a major site for fibre-induced pulmonary diseases. Studies on intravenous injection show that CNT in blood circulation are cleared relatively fast with a half-life of minutes or hours. The major target organs were the same...

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Development of the Gecko (Pachydactylus turneri) Animal Model during Foton M-2 to Study Comparative Effects of Microgravity in Terrestrial and Aquatic Organisms

    Science.gov (United States)

    Almeida, E. A.; Roden, C.; Phillips, J. A.; Globus, R. K.; Searby, N.; Vercoutere, W.; Morey-Holton, E.; Gulimova, V.; Saveliev, S.; Tairbekov, M.; hide

    2006-01-01

    Terrestrial organisms exposed to microgravity during spaceflight experience degeneration in bone, muscle, and possibly other tissues that require gravity-mediated mechanical stimulation for normal regenerative growth. In the Gecko experiment aboard Foton M-2, we flew for the first time, five terrestrial Pachydactylus turneri specimens to develop a model of microgravity effects comparable to the newt Pleurodeles waltl, a well-established model organism for spaceflight. These lower vertebrate species have similar body plans and size, are poikilothermic, have tissue regenerative ability, and are adapted to moderate periods of fasting. Furthermore the gecko (Pachydactylus) can also survive prolonged periods without water. In pre-flight control experiments and after a 16-day Foton M-2 spaceflight without food or water, the geckos were recovered and showed no apparent negative health effects. However, detailed analysis of bone mass and architecture by micro Computed Tomography { pCT), showed that both synchronous control and spaceflight animals lost significant amounts of cancellous bone in the distal femur and humerus relative to basal controls. In addition, cell cycle analysis of 30h post-flight liver tissue reveals a shift of DNA content from G2 and S to G1, both in spaceflight and synchronous controls. Together, these results suggest that housing conditions alone induce rapid catabolism of cancellous bone and reduced normal tissue regeneration. Further use of the gecko Puchydactylus turneri as a spaceflight model requires modification of housing conditions, possibly by including water and food, or changing other factors such as eliminating housing stresses to obtain stable bone structure and tissue regeneration during spaceflight experiments.

  4. 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.

  5. 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.

  6. 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.

  7. Study of crotoxin on the induction of paralysis in extraocular muscle in animal model Estudo da crotoxina na indução de paralisia da musculatura extraocular em modelo animal

    Directory of Open Access Journals (Sweden)

    Geraldo de Barros Ribeiro

    2012-10-01

    Full Text Available PURPOSE: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A. METHODS: The crotoxin, with LD50 of 1.5 µg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 µg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. RESULTS: The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 µg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 µg. CONCLUSION: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 µg was able to induce similar effects as botulinum toxin type A.OBJETIVO: A

  8. 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.

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

    Science.gov (United States)

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