WorldWideScience

Sample records for cancer animal model

  1. Animal Models of Colorectal Cancer

    Science.gov (United States)

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

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

  2. ANIMAL MODELS OF CANCER: A REVIEW

    OpenAIRE

    Archana M Navale

    2013-01-01

    Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primi...

  3. ANIMAL MODELS OF CANCER: A REVIEW

    Directory of Open Access Journals (Sweden)

    Archana M. Navale

    2013-01-01

    Full Text Available Cancer is the second leading cause of death worldwide. In USA three persons out of five will develop some type of cancer. Beyond these statistics of mortality, the morbidity due to cancer presents a real scary picture. Last 50 years of research has rendered some types of cancer curable, but still the major fear factor associated with this disease is unchanged. Animal models are classified according to the method of induction of cancer in the animal. Spontaneous tumor models are the most primitive models. Although these models show good resemblance to the natural disease in humans, they were not capable of keeping pace with developing experimental therapeutics programs. It has therefore been necessary to take a further step towards artificiality, away from the clinical problem in the search for satisfactory testing method. From this step, the journey of artificially induced tumor models started. It is possible to induce cancer reproducibly in animals by exposing them to various agents and now, by transplanting tumor cells or tissue. The development of Genetically Engineered Animal models has provided a great help in knowing the disease. This article takes a review of present animal models used in anti-cancer drug discovery.

  4. Animal models of ovarian cancer

    OpenAIRE

    Shaw Tanya J; Vanderhyden Barbara C; Ethier Jean-François

    2003-01-01

    Abstract Ovarian cancer is the most lethal of all of the gynecological cancers and can arise from any cell type of the ovary, including germ cells, granulosa or stromal cells. However, the majority of ovarian cancers arise from the surface epithelium, a single layer of cells that covers the surface of the ovary. The lack of a reliable and specific method for the early detection of epithelial ovarian cancer results in diagnosis occurring most commonly at late clinical stages, when treatment is...

  5. Animal Models of Cancer Pain

    OpenAIRE

    Pacharinsak, Cholawat; Beitz, Alvin

    2008-01-01

    Modern cancer therapies have significantly increased patient survival rates in both human and veterinary medicine. Since cancer patients live longer they now face new challenges resulting from severe, chronic tumor-induced pain. Unrelieved cancer pain significantly decreases the quality of life of such patients; thus the goal of pain management is to not only to alleviate pain, but also to maintain the patient's physiological and psychological well-being. The major impediment for developing n...

  6. 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 differ

  7. Emerging and Evolving Ovarian Cancer Animal Models

    OpenAIRE

    Bobbs, Alexander S; Jennifer M. Cole; Cowden Dahl, Karen D.

    2015-01-01

    Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect ...

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

    International Nuclear Information System (INIS)

    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

  9. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  10. Establishing of the Transplanted Animal Models for Human Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Xingli Zhang; Jinchang Wu

    2009-01-01

    Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision,radiotherapy,chemotherapy,and gene therapy,the 5 year survival rate is only 15% in the USA.Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer,its progression,invasion and metastasis.Transplanted lung cancer models are of special interest and are widely used today.Such models are essential tools in accelerating development of new therapies for lung cancer.In this communication we will present a brief overview of the hosts,sites and pathways used to establish transplanted animal lung tumor models.

  11. Lost in translation: animal models and clinical trials in cancer treatment

    OpenAIRE

    Mak, Isabella WY; Evaniew, Nathan; Ghert, Michelle

    2014-01-01

    Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal mo...

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

    Directory of Open Access Journals (Sweden)

    Cekanova M

    2014-10-01

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

  13. The Use of Animal Models for Cancer Chemoprevention Drug Development

    OpenAIRE

    Steele, Vernon E.; Lubet, Ronald A.

    2010-01-01

    Animal models currently are used to assess the efficacy of potential chemopreventive agents, including synthetic chemicals, chemical agents obtained from natural products and natural product mixtures. The observations made in these models as well as other data are then used to prioritize agents to determine which are qualified to progress to clinical chemoprevention trials. Organ specific animal models are employed to determine which agents or classes of agents are likely to be the most effec...

  14. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  15. Establishment of Animal Model for Bone Metastasis of Walker 256 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    PANG; Fang-fang; SHEN; Hong-tao; HE; Ming; DONG; Ke-jun; WU; Shao-yong; DOU; Liang; SHI; Yan-jun; ZHANG; Shuang; WANG; Xiao-ming; ZHAO; Qin-zhang; YANG; Xu-ran; XU; Yong-ning; LAN; Xiao-xi; CAI; Li; JIANG; Shan

    2013-01-01

    Bone metastasis is a common complication of cancer.It often occurs in lung,breast and prostate cancer,and may cause osteolytic lesions,or cause few osteoblastic lesions.It has already advanced cancer When cancer metastasis to bone,which usually cannot be cured.It is one of the important factors leading to the death of cancer patients.Studying animal model of bone

  16. 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...

  17. Current Studies of Acupuncture in Cancer-Induced Bone Pain Animal Models

    OpenAIRE

    Hee Kyoung Ryu; Yong-Hyeon Baek; Yeon-Cheol Park; Byung-Kwan Seo

    2014-01-01

    Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR can...

  18. A WKYMVm-containing combination elicits potent anti-tumor activity in heterotopic cancer animal model.

    Directory of Open Access Journals (Sweden)

    Sang Doo Kim

    Full Text Available The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm, 5-fluoro-uracil (5-FU, and mature dendritic cells (mDCs against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK cells into the tumor. The production of two cytokines, IFN-γ and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.

  19. In vivo models for cancer stem cell research: a practical guide for frequently used animal models and available biomarkers.

    Science.gov (United States)

    Skidan, I; Steiniger, S C J

    2014-04-01

    The identification of a rare population of cancer stem cells whose presence in tumors is believed to determine their growth and metastatic activity, has provided a novel approach for targeted anti-cancer therapy. At the in vivo stage of the development of new therapeutic approaches for killing cancer stem cells, the most significant issues are the appropriate choice of rational animal models that offer the option to select animal species, strains and substrains, essential techniques for the inoculation of tumors, and methods of tumor detection in animals. The identification and validation of various types of cancer stem cell markers, which could serve as potential marker(s) of therapeutic efficacy of applied drugs, is a considerable challenge. The aim of this review is to provide a guide for the in vivo study of novel therapeutics that target cancer stem cells. This review describes frequently used mouse solid tumor models and evaluates their usefulness for cancer stem cell research. The classification of existing compounds that are used in today's experimental anti-cancer stem cell therapy and examples of exploratory first-in-human studies using these compounds for selective elimination of cancer stem cells will also be discussed. Finally, this review will examine the current status of available cancer stem cell markers, and highlight several important cancer stem cell properties that are still not well understood, but could influence the anti-cancer drug development process. PMID:24781726

  20. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    Science.gov (United States)

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans. PMID:25768976

  1. Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines

    OpenAIRE

    Rathore, Kusum; Cekanova, Maria

    2014-01-01

    Background Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer. Methods Four K9TCC cell lines were established from naturally-occurring...

  2. Cancer chemoprevention by phytochemicals: potential molecular targets,biomarkers and animal models

    Institute of Scientific and Technical Information of China (English)

    Ki Han KWON; Avantika BARVE; Siwang YU; Mou-Tuan HUANG; Ah-Ng Tony KONG

    2007-01-01

    Recent studies have strongly indicated that certain daily-consumed dietary phytochemicals could have cancer protective effects against transgenic mice can-cer models and cancers mediated by carcinogens, irradiations and carcinogenic metabolites derived from exogenous or endogenous sources. The cancer-protec-tive effects elicited by these dietary compounds are believed to be due at least in part to the induction of cellular defense systems including the detoxifying and antioxidant enzymes system, as well as the inhibition of anti-inflammatory and anti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death. In this review, we summarize the potential mechanisms including the modu-lation of nuclear factor kappaB (NF-κB), cyclooxygenases-2 (COX-2), activator protein-1 (AP-1), mitogen-activated protein kinases (MAPKs) and the induction of phase Ⅱ cellular detoxifying and antioxidant enzymes mediated mainly by the antioxidant response elements (ARE) within the promoter regions of these genes through nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap 'n' collar (CNC) family of the basic region-leucine zipper transcription factor. In addition, we also review several animal models of carcinogenesis and cancer chemopreventive efficacy studies of these animal models using dietary chemopreventive compounds. Finally, we discuss the cellular signaling cascades mediated by Nrf2, NF-κB, AP-1, MAPKs and COX-2, which have been considered to play pivotal roles in tumor initiation, promotion and progression processes,and could be promising molecular targets for the design of drugs targeting cancer prevention and therapy.

  3. Quantitative Diagnosis of Tongue Cancer from Histological Images in an Animal Model

    Science.gov (United States)

    Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo Georgia; Fei, Baowei

    2016-01-01

    We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin (H&E) stained tissue from tongue sections were captured for classifying tumor and non-tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer.

  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. NTP Workshop: Animal Models for the NTP Rodent Cancer Bioassay: Stocks and Strains - Should We Switch?

    OpenAIRE

    King-Herbert, Angela; Thayer, Kristina

    2006-01-01

    The National Toxicology Program (NTP) hosted a workshop, “Animal Models for the NTP Rodent Cancer Bioassay: Strains & Stocks -- Should We Switch?” on June 16-17, 2005, at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, NC. The workshop’s objectives were to determine (1) whether the currently used models, the F344/N rat and B6C3F1/N mouse, continue to be appropriate to identify substances that may pose a carcinogenic hazard for humans and (2) whether ...

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

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-07-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. Preclinical imaging and treatment of cancer: the use of animal models beyond rodents.

    Science.gov (United States)

    Axiak-Bechtel, S M; Maitz, C A; Selting, K A; Bryan, J N

    2015-09-01

    The development of novel radiopharmaceutical agents for imaging and therapy of neoplastic diseases relies on accurate and reproducible animal models. Rodent models are often used to demonstrate the proof-of-principle tracer and therapeutic agent development, but their small size can make tissue sampling challenging. The dosimetry of decay emissions in the much smaller rodent tumors do not model dosimetry in human tumors well. In addition, rodent models of cancer represent a simplified version of a very complex process. Spontaneous tumors are heterogenous and the response to intervention can be unpredictable; tumor cells can adopt alternate signaling pathways and modify their interaction with the microenvironment. These inconsistencies, while present in humans, are difficult to fully reproduce in a genetically-engineered rodent model. Companion animals, primarily dogs and cats, offer translational models that more accurately reflect the intricate nature of spontaneous neoplasia in humans. Their larger size facilitates tissue and blood sampling when needed, and allows radiopharmaceutical tracers to be studied on human-scale imaging systems to better mimic the clinical application of the agent. This article will review the growing body of literature surrounding the use of radiopharmaceutical agents for both imaging and therapy in companion dogs and cats. Previous investigations have been performed both for the advancement of routine, high-level veterinary care, and in the context of translational research from which the results of imaging and treatment can be readily applied to people. Studies utilizing the spontaneously occurring cancer model in companion animals involving positron emission tomography, radiotracers, dosimetry, theranostics, targeted radiopharmaceuticals, brachytherapy, and boron neutron capture therapy are discussed. PMID:26200223

  10. Preclinical imaging and treatment of cancer: the use of animal models beyond rodents

    International Nuclear Information System (INIS)

    The development of novel radiopharmaceutical agents for imaging and therapy of neoplastic diseases relies on accurate and reproducible animal models. Rodent models are often used to demonstrate the proof-of-principle tracer and therapeutic agent development, but their small size can make tissue sampling challenging. The dosimetry of decay emissions in the much smaller rodent tumors do not model dosimetry in human tumors well. In addition, rodent models of cancer represent a simplified version of a very complex process. Spontaneous tumors are heterogenous and the response to intervention can be unpredictable; tumor cells can adopt alternate signaling pathways and modify their interaction with the microenvironment. These inconsistencies, while present in humans, are difficult to fully reproduce in a genetically-engineered rodent model. Companion animals, primarily dogs and cats, offer translational models that more accurately reflect the intricate nature of spontaneous neoplasia in humans. Their larger size facilitates tissue and blood sampling when needed, and allows radiopharmaceutical tracers to be studied on human-scale imaging systems to better mimic the clinical application of the agent. This article will review the growing body of literature surrounding the use of radiopharmaceutical agents for both imaging and therapy in companion dogs and cats. Previous investigations have been performed both for the advancement of routine, high-level veterinary care, and in the context of translational research from which the results of imaging and treatment can be readily applied to people. Studies utilizing the spontaneously occurring cancer model in companion animals involving positron emission tomography, radiotracers, dosimetry, theranostics, targeted radiopharmaceuticals, brachytherapy, and boron neutron capture therapy are discussed.

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

    Directory of Open Access Journals (Sweden)

    Jiarong Chen

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

  12. Functional magnetic resonance imaging in an animal model of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Robert; J; Lewandowski; Aaron; C; Eifler; David; J; Bentrem; Johnathan; C; Chung; Gayle; E; Woloschak; Robert; Ryu; Riad; Salem; Andrew; C; Larson; Reed; A; Omary

    2010-01-01

    AIM: To test the hypotheses that diffusion weighed (DW)and transcatheter intraarterial perfusion (TRIP)magnetic resonance imaging (MRI) can each be used to assess regional differences in tumor function in an animal pancreatic cancer model.METHODS: VX2 tumors were implanted in pancreata of 6 rabbits. MRI and digital subtraction angiography (DSA) were performed 3 wk following implantation. With a 2-French catheter secured in the rabbit's gastroduodenal artery, each rabbit was transferred to an adjacent 1.5T M...

  13. Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Richard M NILES

    2007-01-01

    Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabo-lisrn/action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second prima-ties in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unrespon-sive premalignant lesions.

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

    OpenAIRE

    Cekanova M; Rathore K

    2014-01-01

    Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for pa...

  15. Establishment of animal model for the analysis of cancer cell metastasis during radiotherapy

    International Nuclear Information System (INIS)

    Γ-Ionizing radiation (IR) therapy is one of major therapeutic tools in cancer treatment. Nevertheless, γ-IR therapy failed due to occurrence of metastasis, which constitutes a significant obstacle in cancer treatment. The main aim of this investigation was to construct animal model which present metastasis during radiotherapy in a mouse system in vivo and establishes the molecular mechanisms involved. The C6L transfectant cell line expressing firefly luciferase (fLuc) was treated with γ-IR, followed by immunoblotting, zymography and invasion assay in vitro. We additionally employed the C6L transfectant cell line to construct xenografts in nude mice, which were irradiated with γ-IR. Irradiated xenograft-containing mice were analyzed via survival curves, measurement of tumor size, and bioluminescence imaging in vivo and ex vivo. Metastatic lesions in organs of mice were further assessed using RT-PCR, H & E staining and immunohistochemistry. γ-IR treatment of C6L cells induced epithelial-mesenchymal transition (EMT) and increased cell invasion. In irradiated xenograft-containing mice, tumor sizes were decreased dramatically and survival rates extended. Almost all non-irradiated xenograft-containing control mice had died within 4 weeks. However, we also observed luminescence signals in about 22.5% of γ-IR-treated mice. Intestines or lungs of mice displaying luminescence signals contained several lesions, which expressed the fLuc gene and presented histological features of cancer tissues as well as expression of EMT markers. These findings collectively indicate that occurrences of metastases during γ-IR treatment accompanied induction of EMT markers, including increased MMP activity. Establishment of a murine metastasis model during γ-IR treatment should aid in drug development against cancer metastasis and increase our understanding of the mechanisms underlying the metastatic process

  16. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

    Science.gov (United States)

    Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy; Seneshaw, Mulugeta; Vincent, Robert; Banini, Bubu A.; Kumar, Divya Prasanna; Daita, Kalyani; Min, Hae-Ki; Mirshahi, Faridoddin; Bedossa, Pierre; Sun, Xiaochen; Hoshida, Yujin; Koduru, Srinivas V.; Contaifer, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S.; Sanyal, Arun J.

    2016-01-01

    Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID:27261415

  17. Mechanistic models of bone cancer induction by radium and plutonium in animals compared to humans

    International Nuclear Information System (INIS)

    Two-mutation carcinogenesis models of mice and rats injected with 239Pu and 226Ra have been derived extending previous modellings of beagle dogs injected with 239Pu and 226Ra and radium dial painters. In all cases statistically significant parameters could be derived fitting data from several research groups jointly. This also lead to similarly parametrized models for 239Pu and 226Ra for all species. For each data set not more than five free model parameters were needed to fit the data adequately. From the toxicity ratios of the animal models for 239Pu and 226Ra, together with the human model for 226Ra, an approximate model for the exposure of humans to 239Pu has been derived. Relative risk calculations with this approximate model are in good agreement with epidemiological findings for the plutonium-exposed Mayak workers. This promising result may indicate new possibilities for estimating risks for humans from animal experiments. (authors)

  18. Animal Models for imaging

    OpenAIRE

    Croft, Barbara Y.

    2002-01-01

    Animal models can be used in the study of disease. This chapter discusses imaging animal models to elucidate the process of human disease. The mouse is used as the primary model. Though this choice simplifies many research choices, it necessitates compromises for in vivo imaging. In the future, we can expect improvements in both animal models and imaging techniques.

  19. Re-evaluate the effect of hyperbaric oxygen therapy in cancer - a preclinical therapeutic small animal model study.

    Directory of Open Access Journals (Sweden)

    Sneha Pande

    Full Text Available Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.

  20. Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain

    Science.gov (United States)

    Zhu, Yong Fang; Ungard, Robert; Seidlitz, Eric; Zacal, Natalie; Huizinga, Jan; Henry, James L

    2016-01-01

    Background Bone cancer pain is often severe, yet little is known about mechanisms generating this type of chronic pain. While previous studies have identified functional alterations in peripheral sensory neurons that correlate with bone tumours, none has provided direct evidence correlating behavioural nociceptive responses with properties of sensory neurons in an intact bone cancer model. Results In a rat model of prostate cancer-induced bone pain, we confirmed tactile hypersensitivity using the von Frey test. Subsequently, we recorded intracellularly from dorsal root ganglion neurons in vivo in anesthetized animals. Neurons remained connected to their peripheral receptive terminals and were classified on the basis of action potential properties, responses to dorsal root stimulation, and to mechanical stimulation of the respective peripheral receptive fields. Neurons included C-, Aδ-, and Aβ-fibre nociceptors, identified by their expression of substance P. We suggest that bone tumour may induce phenotypic changes in peripheral nociceptors and that these could contribute to bone cancer pain. Conclusions This work represents a significant technical and conceptual advance in the study of peripheral nociceptor functions in the development of cancer-induced bone pain. This is the first study to report that changes in sensitivity and excitability of dorsal root ganglion primary afferents directly correspond to mechanical allodynia and hyperalgesia behaviours following prostate cancer cell injection into the femur of rats. Furthermore, our unique combination of techniques has allowed us to follow, in a single neuron, mechanical pain-related behaviours, electrophysiological changes in action potential properties, and dorsal root substance P expression. These data provide a more complete understanding of this unique pain state at the cellular level that may allow for future development of mechanism-based treatments for cancer-induced bone pain. PMID:27030711

  1. Ovine pulmonary adenocarcinoma as an animal model of progressive lung cancer and the impact of nutritional selenium supply.

    Science.gov (United States)

    Humann-Ziehank, Esther; Wolf, Petra; Renko, Kostja; Schomburg, Lutz; Ludwig Bruegmann, Michael; Andreae, Arnim; Brauer, Carsten; Ganter, Martin

    2011-01-01

    Jaagsiekte sheep retrovirus (JSRV) is known to induce ovine pulmonary adenocarcinoma (OPA). Several studies have suggested an influence of selenium (Se) status on cancer progression. Thus, combining OPA with a defined Se supply might serve as a suitable animal model to study the impact of Se on lung cancer progression. 16 naturally JSRV-infected sheep were divided into 2 treatment groups receiving (a) CT) was performed repeatedly and evaluated using a CT-OPA-score system. Liver biopsies were taken three-monthly, blood samples were collected biweekly to study treatment effects on Se concentrations and glutathione peroxidase (GPx) activity. Cell pellets from bronchoalveolar lavage fluid (BALF) were tested for JSRV by PCR to approve the infection. To date, four animals of the ongoing study have been euthanised. Autopsy and histopathology were performed and correlated to CT analysis. JSRV was detected in BALF cell pellets. Progression of lung tumours was monitored successfully by repeated CT examinations, enabling the detection of even small nodules or increased lung density. Histopathology revealed bronchioloalveolar adenocarcinoma in lung areas suspicious to be OPA from CT evaluation. Score-based analysis of CT images for quantifying tumour progression proved as a valuable tool. Se concentration and GPx activity increased in liver and serum of group b and verified the efficiency of different feeding regime. In conclusion, OPA along with CT, autopsy/histopathology, trace element and enzyme activity analysis provide a suitable large animal model to examine the impact of Se supply on lung tumourigenesis.

  2. Common cancer in a wild animal: the California sea lion (Zalophus californianus) as an emerging model for carcinogenesis.

    Science.gov (United States)

    Browning, Helen M; Gulland, Frances M D; Hammond, John A; Colegrove, Kathleen M; Hall, Ailsa J

    2015-07-19

    Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studying neoplasia in wild animals is difficult and especially challenging in marine mammals owing to their inaccessibility, lack of exposure history, and ethical, logistical and legal limits on experimentation. Despite this, California sea lions (Zalophus californianus) offer an opportunity to investigate risk factors for neoplasia development that have implications for terrestrial mammals and humans who share much of their environment and diet. A relatively accessible California sea lion population on the west coast of the USA has a high prevalence of urogenital carcinoma and is regularly sampled during veterinary care in wildlife rehabilitation centres. Collaborative studies have revealed that genotype, persistent organic pollutants and a herpesvirus are all associated with this cancer. This paper reviews research to date on the epidemiology and pathogenesis of urogenital carcinoma in this species, and presents the California sea lion as an important and currently underexploited wild animal model of carcinogenesis.

  3. 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?...

  4. Cytosolic phospholipaseA2 inhibition with PLA-695 radiosensitizes tumors in lung cancer animal models.

    Directory of Open Access Journals (Sweden)

    Dinesh Thotala

    Full Text Available Lung cancer remains the leading cause of cancer deaths in the United States and the rest of the world. The advent of molecularly directed therapies holds promise for improvement in therapeutic efficacy. Cytosolic phospholipase A2 (cPLA2 is associated with tumor progression and radioresistance in mouse tumor models. Utilizing the cPLA2 specific inhibitor PLA-695, we determined if cPLA2 inhibition radiosensitizes non small cell lung cancer (NSCLC cells and tumors. Treatment with PLA-695 attenuated radiation induced increases of phospho-ERK and phospho-Akt in endothelial cells. NSCLC cells (LLC and A549 co-cultured with endothelial cells (bEND3 and HUVEC and pre-treated with PLA-695 showed radiosensitization. PLA-695 in combination with irradiation (IR significantly reduced migration and proliferation in endothelial cells (HUVEC & bEND3 and induced cell death and attenuated invasion by tumor cells (LLC &A549. In a heterotopic tumor model, the combination of PLA-695 and radiation delayed growth in both LLC and A549 tumors. LLC and A549 tumors treated with a combination of PLA-695 and radiation displayed reduced tumor vasculature. In a dorsal skin fold model of LLC tumors, inhibition of cPLA2 in combination with radiation led to enhanced destruction of tumor blood vessels. The anti-angiogenic effects of PLA-695 and its enhancement of the efficacy of radiotherapy in mouse models of NSCLC suggest that clinical trials for its capacity to improve radiotherapy outcomes are warranted.

  5. Efficacy of HPV-16 E7 Based Vaccine in a TC-1 Tumoric Animal Model of Cervical Cancer - page 483

    Directory of Open Access Journals (Sweden)

    Maryam Fazeli

    2011-01-01

    Full Text Available Objective: The human papillomavirus as an etiological agent of cervical cancer doesnot grow adequately in tissue culture systems. The tumor cell line TC-1 continuously expressesthe E6 and E7 oncogenic proteins of HPV, and is considered a suitable tool inlaboratory investigations and vaccine researches against cervical cancer.Materials and Methods: The TC-1 cell line was grown in RPMI 1650 supplemented with10% FBS, glutamine and antibiotics, and was used for tumor development in mice. Six toseven week-old tumor bearing C57BL/6 mice were divided into 3 groups consisting of 7mice per group. The first group received pcDNA-E7, the second group received pcDNA3,and the third group received phosphate buffered saline (PBS. The treated animals weremonitored for their tumor size progression and survival. At last, the tumoric tissues fromautopsied animals were fixed and examined with Mayer's hematoxylin and eosin (H&E.All experiments were done in accordance with guidelines of the Laboratory Animal EthicalCommission of Tarbiat Modares University. Data analysis was performed using the onewayANOVA followed by Tukey's test in both experimental and control groups. A p-value<0.05 was considered significant.Results: There were significant decreases in tumor growth; there were also improvementsin survival among mice in the treated groups (p<0.041. H&E stained sections fromuntreated mice were studied independently in a blinded fashion by two observers andshowed malignant neoplasms composed of severely pleomorphic tumor cells with nuclearenlargement, high nuclear-cytoplasmic (N/C ratios, and prominent nucleoli in solid andfascicular patterns of growth. High mitotic activity with extensive necrosis was also notedin both test and control groups.Conclusion: The TC-1 lung metastatic model can be used to test the efficacy of variousE7-based therapeutic cancer vaccine strategies for cervical cancer and the prevention ofHPV-related neoplasia.

  6. Animal models for human diseases.

    Science.gov (United States)

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  7. Animal models of asthma

    OpenAIRE

    Bates, Jason H.T.; Rincon, Mercedes; Irvin, Charles G.

    2009-01-01

    Studies in animal models form the basis for much of our current understanding of the pathophysiology of asthma, and are central to the preclinical development of drug therapies. No animal model completely recapitulates all features of the human disease, however. Research has focused primarily on ways to generate allergic inflammation by sensitizing and challenging animals with a variety of foreign proteins, leading to an increased understanding of the immunological factors that mediate the in...

  8. Animal Model of Dermatophytosis

    OpenAIRE

    Tsuyoshi Shimamura; Nobuo Kubota; Kazutoshi Shibuya

    2012-01-01

    Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host’s normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the presen...

  9. Models for comparing lung-cancer risks in radon- and plutonium-exposed experimental animals

    International Nuclear Information System (INIS)

    Epidemiologic studies of radon-exposed underground miners have provided the primary basis for estimating human lung-cancer risks resulting from radon exposure. These studies are sometimes used to estimate lung-cancer risks resulting from exposure to other alpha- emitters as well. The latter use, often referred to as the dosimetric approach, is based on the assumption that a specified dose to the lung produces the same lung-tumor risk regardless of the substance producing the dose. At Pacific Northwest Laboratory, experiments have been conducted in which laboratory rodents have been given inhalation exposures to radon and to plutonium (239PuO2). These experiments offer a unique opportunity to compare risks, and thus to investigate the validity of the dosimetric approach. This comparison is made most effectively by modeling the age-specific risk as a function of dose in a way that is comparable to analyses of human data. Such modeling requires assumptions about whether tumors are the cause of death or whether they are found incidental to death from other causes. Results based on the assumption that tumors are fatal indicate that the radon and plutonium dose-response curves differ, with a linear function providing a good description of the radon data, and a pure quadratic function providing a good description of the plutonium data. However, results based on the assumption that tumors are incidental to death indicate that the dose-response curves for the two exposures are very similar, and thus support the dosimetric approach. 14 refs., 2 figs., 6 tabs

  10. Research Progress of Transgenic Animal Models of Lung Cancer%转基因肺癌动物模型研究进展

    Institute of Scientific and Technical Information of China (English)

    张修彦; 詹纯列

    2012-01-01

    Lung eaneer is one of the common malignant tumors in the world. Animal models of lung cancer have models of lung cancer are more similar to human lung cancer and are better for studies on the etiology and pathogenesis of lung cancer. This article is focused on the research progress of transgenic animal models of lung cancer in recent years.%肺癌是世界各国常见的恶性肿瘤,肺癌动物模型在人类肺癌病因、诊断、治疗等方面发挥重要的作用.其中转基因肺癌模型能够更好的模拟肺癌,更有利于肺癌病因及发病过程的研究.本文介绍了近年来转基因肺癌模型的研究进展.

  11. Animal models of scoliosis.

    Science.gov (United States)

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

    2015-04-01

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

  12. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  13. Challenges in pre-clinical testing of anti-cancer drugs in cell culture and in animal models

    OpenAIRE

    HogenEsch, Harm; Yu Nikitin, Alexander

    2012-01-01

    Experiments with cultures of human tumor cell lines, xenografts of human tumors into immunodeficient mice, and mouse models of human cancer are important tools in the development and testing of anti-cancer drugs. Tumors are complex structures composed of genetically and phenotypically heterogeneous cancer cells that interact in a reciprocal manner with the stromal microenvironment and the immune system. Modeling the complexity of human cancers in cell culture and in mouse models for preclinic...

  14. Animal models of schizophrenia

    OpenAIRE

    Jones, CA; Watson, DJG; Fone, KCF

    2011-01-01

    Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rod...

  15. Animal Models of Fibromyalgia

    OpenAIRE

    Nagakura, Yukinori; Ito, Hiroyuki; Shimizu, Yasuaki

    2012-01-01

    Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. T...

  16. Neoplasms escape selective COX-2 inhibition in an animal model of breast cancer.

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

    Cyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.

  17. The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

    International Nuclear Information System (INIS)

    The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 105, 1 × 106 and 5 × 106 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 106 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 106 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

  18. Comparative uptakes and biodistributions of internalizing vs. noninternalizing copper-64 radioimmunoconjugates in cell and animal models of colon cancer

    International Nuclear Information System (INIS)

    Copper-64-labeled monoclonal antibodies (mAbs) have previously demonstrated unexpectedly effective tumor control in rodent models of cancer at relatively low tumor-absorbed radiation doses. This property has been associated with delivery platforms resulting in cellular internalization. The purpose of the present studies was to evaluate the in vitro internalization and in vivo distribution of a two-antibody model of 64Cu radioimmunotherapy (RIT) in the same cell and animal models of cancer. Biodistributions of an internalizing antibody, cBR96, and a noninternalizing antibody, cT84.66, labeled with 64Cu, were obtained in nude mice bearing LS174T colon carcinoma xenografts from 15 min to 48 h. The 64Cu-DOTA-cBR96 conjugate demonstrated rapid tumor uptake, reaching 20.2% ID/g at 3 h and peaking at 35.4% ID/g by 24 h. Tumor accumulation of 64Cu-DOTA-cT84.66 was more gradual, 8.19% ID/g at 3 h and 43.8% ID/g by 24 h, but maximum uptake was not statistically different from 64Cu-DOTA-cBR96. Mouse xenograft dosimetry was estimated to be 1128 rad/mCi (304.9 mGy/MBq) for 64Cu-DOTA-cBR96 and 1409 rad/mCi (380.5 mGy/MBq) for 64Cu-DOTA-cT84.66. In LS174T cells, internalized radioactivity increased by a factor of 3.8 over 4 h for 64Cu-DOTA-cBR96, but remained unchanged 64Cu-DOTA-cT84.66. When normalized to uptake at 1 h, cellular efflux of 64Cu was essentially identical for both mAbs. The biodistributions and tumor dosimetry of these internalizing and noninternalizing radiolabeled mAbs were sufficiently similar for direct comparison of the therapeutic efficacies of low doses of 64Cu RIT agents in the same animal model of cancer

  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. Bispecific antibodies for treatment of cancer in experimental animal models and man

    NARCIS (Netherlands)

    Kroesen, Bart-Jan; Helfrich, Wijnand; Molema, Ingrid; de Leij, Lou

    1998-01-01

    Immunotherapy is a powerful anti-cancer treatment modality. However, despite numerous encouraging results obtained in pre-clinical studies, a definite breakthrough towards an established clinical treatment modality has as yet not occurred. Antibodies against tumor antigens have been shown to localis

  1. Animal models of ADHD.

    Science.gov (United States)

    Bari, A; Robbins, T W

    2011-01-01

    Studies employing animal models of attention-deficit/hyperactivity disorder (ADHD) present clear inherent advantages over human studies. Animal models are invaluable tools for the study of underlying neurochemical, neuropathological and genetic alterations that cause ADHD, because they allow relatively fast, rigorous hypothesis testing and invasive manipulations as well as selective breeding. Moreover, especially for ADHD, animal models with good predictive validity would allow the assessment of potential new therapeutics. In this chapter, we describe and comment on the most frequently used animal models of ADHD that have been created by genetic, neurochemical and physical alterations in rodents. We then discuss that an emerging and promising direction of the field is the analysis of individual behavioural differences among a normal population of animals. Subjects presenting extreme characteristics related to ADHD can be studied, thereby avoiding some of the problems that are found in other models, such as functional recovery and unnecessary assumptions about aetiology. This approach is justified by the theoretical need to consider human ADHD as the extreme part of a spectrum of characteristics that are distributed normally in the general population, as opposed to the predominant view of ADHD as a separate pathological category. PMID:21287324

  2. 肝癌动物模型的研究及进展%Research Progress in Animal Models of Liver Cancer

    Institute of Scientific and Technical Information of China (English)

    申凤鸽

    2011-01-01

    [Objective]To establish good animal models of liver cancer and serve treatment of liver cancer in humans. [Method J Several common animal models of liver cancer were introduced briefly. [ Result] The commonly used animal models include C57BL/6J mouse model of or-thotopic liver cancer induced with Hepal-6 cells,nude mouse model of liver cancer established with Hep_G2 cell lines,rat liver cancer model established through direct transplantation or direct injection,HU-PBL-SCID mice model,and other transplanted liver cancer models or genetic liver cancer models. [ Conclusion] Animal model is an important means and platform for experimental studies. To establish animal models of liver cancer is of important significance for studies on pathogenesis, diagnosis and treatment of liver cancer.%[目的]建立良好的肝癌动物模型,为人类治疗肝癌服务.[方法]简单介绍几种比较常见的肝癌动物模型.[结果]目前比较常用的动物模型有:Hepal-6细胞诱发C57BL /6J小鼠原位肝癌模型、采用Hep_G2细胞株建立裸鼠肝癌模型、直接移植法建立大鼠肝癌模型、直接注入法建立大鼠肝癌模型、免疫重建荷人高转移肝癌SCD鼠模型、其他移植性肝癌模型和基因性肝癌模型.[结论]动物模型是进行试验研究的重要手段和平台,建立肝癌动物模型对肝癌发生机制、诊断与治疗研究有很重要的意义.

  3. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mengmeng Lv

    Full Text Available The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies.Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction.Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI of 0.20 (0.12, 0.34 relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer.Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

  4. 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. PMID:27317993

  5. Animal Models of Atherosclerosis

    OpenAIRE

    Godfrey S Getz; Reardon, Catherine A

    2012-01-01

    Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to...

  6. SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs.

    Science.gov (United States)

    Blyth, Karen; Carter, Phil; Morrissey, Bethny; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

    2016-04-01

    Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating to the original projects. Despite being developed at considerable cost, this material is an invisible and hence an underutilised resource, which often ends up being discarded. Within the breast cancer research community there is both a need and desire to make this valuable material available for researchers. Lack of a coordinated system for visualisation and localisation of this has prevented progress. To fulfil this unmet need, we have developed a novel initiative called Sharing Experimental Animal Resources: Coordinating Holdings-Breast (SEARCHBreast) which facilitates sharing of archival tissue between researchers on a collaborative basis and, de facto will reduce overall usage of animal models in breast cancer research. A secure searchable database has been developed where researchers can find, share, or upload materials related to animal models of breast cancer, including genetic and transplant models. SEARCHBreast is a virtual compendium where the physical material remains with the original laboratory. A bioanalysis pipeline is being developed for the analysis of transcriptomics data associated with mouse models, allowing comparative study with human and cell line data. Additionally, SEARCHBreast is committed to promoting the use of humanised breast tissue models as replacement alternatives to animals. Access to this unique resource is freely available to all academic researchers following registration at https://searchbreast.org . PMID:27083180

  7. SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs.

    Science.gov (United States)

    Blyth, Karen; Carter, Phil; Morrissey, Bethny; Chelala, Claude; Jones, Louise; Holen, Ingunn; Speirs, Valerie

    2016-04-01

    Animal models have contributed to our understanding of breast cancer, with publication of results in high-impact journals almost invariably requiring extensive in vivo experimentation. As such, many laboratories hold large collections of surplus animal material, with only a fraction being used in publications relating to the original projects. Despite being developed at considerable cost, this material is an invisible and hence an underutilised resource, which often ends up being discarded. Within the breast cancer research community there is both a need and desire to make this valuable material available for researchers. Lack of a coordinated system for visualisation and localisation of this has prevented progress. To fulfil this unmet need, we have developed a novel initiative called Sharing Experimental Animal Resources: Coordinating Holdings-Breast (SEARCHBreast) which facilitates sharing of archival tissue between researchers on a collaborative basis and, de facto will reduce overall usage of animal models in breast cancer research. A secure searchable database has been developed where researchers can find, share, or upload materials related to animal models of breast cancer, including genetic and transplant models. SEARCHBreast is a virtual compendium where the physical material remains with the original laboratory. A bioanalysis pipeline is being developed for the analysis of transcriptomics data associated with mouse models, allowing comparative study with human and cell line data. Additionally, SEARCHBreast is committed to promoting the use of humanised breast tissue models as replacement alternatives to animals. Access to this unique resource is freely available to all academic researchers following registration at https://searchbreast.org.

  8. Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

    Science.gov (United States)

    Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

    2014-05-01

    Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here

  9. Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal model

    Directory of Open Access Journals (Sweden)

    Qihua GU

    2008-08-01

    Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H&E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

  10. Animal models of sepsis

    OpenAIRE

    Fink, Mitchell P.

    2013-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, ...

  11. Fate of PLA and PCL-Based Polymeric Nanocarriers in Cellular and Animal Models of Triple-Negative Breast Cancer.

    Science.gov (United States)

    Sitia, Leopoldo; Ferrari, Raffaele; Violatto, Martina B; Talamini, Laura; Dragoni, Luca; Colombo, Claudio; Colombo, Laura; Lupi, Monica; Ubezio, Paolo; D'Incalci, Maurizio; Morbidelli, Massimo; Salmona, Mario; Moscatelli, Davide; Bigini, Paolo

    2016-03-14

    An integrated platform to assess the interaction between nanocarriers and biological matrices has been developed by our group using poly methyl-methacrylate nanoparticles. In this study, we exploited this platform to evaluate the behavior of two biodegradable formulations, poly-ε-caprolactone (PCL3) and poly lactic-acid (PLA8), respectively, in cellular and animal models of triple-negative breast cancer (TNBC). Both NPs shared the main physicochemical parameters (size, shape, ζ-potential) and exclusively differentiated on the material on which they are composed. Our results showed that (1) PLA8 NPs, systemically injected in mice, underwent rapid degradation without penetration into tumors; (2) PLA8 NPs were not internalized in the human TNBC cell line (MDA-MB-231); (3) PCL3 NPs had a longer bioavailability, reached the tumor parenchyma, and efficiently penetrated in MDA-MB-231 cells. Our data highlight the relevance of the material selection to both improve bioavailability and target tropism, and make PCL3 NPs an interesting tool for the development of nanodrugs against TNBC. PMID:26791775

  12. Animal models of candidiasis.

    Science.gov (United States)

    Clancy, Cornelius J; Cheng, Shaoji; Nguyen, Minh Hong

    2009-01-01

    Animal models are powerful tools to study the pathogenesis of diverse types of candidiasis. Murine models are particularly attractive because of cost, ease of handling, technical feasibility, and experience with their use. In this chapter, we describe methods for two of the most popular murine models of disease caused by Candida albicans. In an intravenously disseminated candidiasis (DC) model, immunocompetent mice are infected by lateral tail vein injections of a C. albicans suspension. Endpoints include mortality, tissue burdens of infection (most importantly in the kidneys, although spleens and livers are sometimes also assessed), and histopathology of infected organs. In a model of oral/esophageal candidiasis, mice are immunosuppressed with cortisone acetate and inoculated in the oral cavities using swabs saturated with a C. albicans suspension. Since mice do not die from oral candidiasis in this model, endpoints are tissue burden of infection and histopathology. The DC and oral/esophageal models are most commonly used for studies of C. albicans virulence, in which the disease-causing ability of a mutant strain is compared with an isogenic parent strain. Nevertheless, the basic techniques we describe are also applicable to models adapted to investigate other aspects of pathogenesis, such as spatiotemporal patterns of gene expression, specific aspects of host immune response and assessment of antifungal agents, immunomodulatory strategies, and vaccines.

  13. New insights from animal models of colon cancer: inflammation control as a new facet on the tumor suppressor APC gem

    Directory of Open Access Journals (Sweden)

    Zeineldin M

    2015-01-01

    Full Text Available Maged Zeineldin, Kristi L Neufeld Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA Abstract: Colorectal cancer (CRC is one of the most common causes of cancer-related deaths worldwide. As with other cancers, CRC is a genetic disease, however, several risk factors including diet and chronic colitis predispose to the disease. Mutations in the tumor suppressor adenomatous polyposis coli (APC initiate most cases of CRC. Recent data from mouse models suggest that APC mutations and colitis are not completely independent factors in colorectal carcinogenesis. Here, we review the evidence supporting an interaction between APC mutations and chronic colitis. We will also discuss possible pathophysiologic mechanisms behind this interaction. Keywords: rodent model, colon cancer, adenomatous polyposis coli, APC, tumor suppressor, inflammatory bowel disease 

  14. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    Science.gov (United States)

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  15. An Interactive Tool for Animating Biology, and Its Use in Spatial and Temporal Modeling of a Cancerous Tumor and Its Microenvironment.

    Directory of Open Access Journals (Sweden)

    Naamah Bloch

    Full Text Available The ability to visualize the ongoing events of a computational model of biology is critical, both in order to see the dynamics of the biological system in action and to enable interaction with the model from which one can observe the resulting behavior. To this end, we have built a new interactive animation tool, SimuLife, for visualizing reactive models of cellular biology. SimuLife is web-based, and is freely accessible at http://simulife.weizmann.ac.il/. We have used SimuLife to animate a model that describes the development of a cancerous tumor, based on the individual components of the system and its environment. This has helped in understanding the dynamics of the tumor and its surrounding blood vessels, and in verifying the behavior, fine-tuning the model accordingly, and learning in which way different factors affect the tumor.

  16. 肝癌动物模型研究进展%Progress in research on animal models of liver cancer

    Institute of Scientific and Technical Information of China (English)

    黄佳飞; 周洪渊; 张倜

    2014-01-01

    肝癌动物模型的建立具有重要价值。动物模型的建立分为实验动物的选择和肿瘤的来源两部分。因肿瘤的来源不同又可以将模型分为不同的类型,不同类型的模型具有各自相应的特点和局限性。理想的肝癌动物模型应该在生物学习性、生化性质、病理学特征等方面与人类肝癌相类似,并且模型制作过程简便易行。%Asaresult,establishinganimalmodelsoflivercancerisofhighvalue.Therearetwoparts of the establishment of animal models-the selection of laboratory animals and the source of tumors.The animal models could be classified into different patterns due to difference sources of tumor,and these different patterns possess distinctive characters and limitations.The ideally animal models should satisfy the general requirements of biological habits,biochemical properties,and pathological features which are similar with human hepatocel-lular and easy to establish.

  17. Stochastic modelling of animal movement

    OpenAIRE

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

    2010-01-01

    Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal ‘settling down’, accomplished by including one or more focal poi...

  18. Comparison of animal models for the evaluation of radiolabeled androgens

    International Nuclear Information System (INIS)

    Biodistribution of two 18F-labeled androgens and an 124I/125I-labeled androgen were studied in five androgen receptor (prostate) animal models with or lacking sex hormone binding globulin (SHBG). As models for androgen-receptor positive ovarian cancer, xenografts of three human ovarian cancer cell lines were tested in SCID mice. SHBG in the prostate model systems significantly affects the metabolism, clearance, and distribution of the radiolabeled androgens in several tissues, but ovarian cancer animal models were disappointing

  19. Animal Models of Depression: Molecular Perspectives

    OpenAIRE

    Krishnan, Vaishnav; Nestler, Eric J.

    2011-01-01

    Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral ass...

  20. Animal Models of Neuropsychiatric Disorders

    OpenAIRE

    Nestler, Eric J.; Steven E Hyman

    2010-01-01

    Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many key symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression, a...

  1. 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)

    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 7Li). 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 6Li2CO3 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)

  2. Refining Animal Models to Enhance Animal Welfare

    Institute of Scientific and Technical Information of China (English)

    Patricia V.Turner

    2012-01-01

    The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress. It may also refer to procedures used to enhance animal comfort. This paper summarizes considerations for refinements in research animal.

  3. Xenobiotic effects in cancer related pathways-high throughput screening and proof of concept in animal models

    Institute of Scientific and Technical Information of China (English)

    Ursula E. Schumacher

    2013-01-01

    Xenobiotic drugs and chemicals directly interact with DNA, proteins, or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences, in its report, Toxicity Testing in the 21st Century: a Vision and a Strategy[1], proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative, dose-response models based on information from in vitro assays and in vivo biomarkers, which can be used to screen large numbers of chemicals.The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics (drug targets, environmental chemicals) via a set of "sentinel" genes[2] that are functionally interrelated based on evidence weighted functional linkage network (FLN) log-likelihood scores (Linghu et al[3]).

  4. Symptomatic animal models for dystonia

    OpenAIRE

    Wilson, Bethany K.; Hess, Ellen J.

    2013-01-01

    Symptomatic animal models have clinical features consistent with human disorders and are often used to identify the anatomical and physiological processes involved in the expression of symptoms and to experimentally demonstrate causality where it would be infeasible in the patient population. Rodent and primate models of dystonia have identified basal ganglia abnormalities, including alterations in striatal GABAergic and dopaminergic transmission. Symptomatic animal models have also establish...

  5. Imaging anti-angiogenic treatment response with DCE-VCT, DCE-MRI and DWI in an animal model of breast cancer bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Baeuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: t.baeuerle@dkfz-heidelberg.de; Bartling, Soenke [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: s.bartling@dkfz-heidelberg.de; Berger, Martin [Unit of Chemotherapy and Toxicology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: m.berger@dkfz-heidelberg.de; Schmitt-Graeff, Annette [Institute of Pathology, University of Freiburg, Postfach 214, 79002 Freiburg (Germany)], E-mail: annette.schmitt-graeff@uniklinik-freiburg.de; Hilbig, Heidegard [Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103 Leipzig (Germany)], E-mail: Heidegard.Hilbig@medizin.uni-leipzig.de; Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, Radiologische Klinik, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)], E-mail: hans-ulrich.kauczor@med.uni-heidelberg.de; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: s.delorme@dkfz-heidelberg.de; Kiessling, Fabian [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Experimental Molecular Imaging, RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen (Germany)], E-mail: fkiessling@ukaachen.de

    2010-02-15

    As current classification systems for the assessment of treatment response in bone metastasis do not meet the needs of oncologists, new imaging biomarkers are desirable. Therefore, the diagnostic impact of dynamic contrast enhanced (DCE)-volumetric computed tomography (VCT) (descriptive analysis), DCE-MRI (two-compartment model) and diffusion weighted imaging (DWI) for monitoring anti-angiogenic therapy effects of the VEGF antibody bevacizumab in breast cancer bone metastases in rats was studied. Nude rats (n = 8 animals treated with bevacizumab and n = 9 untreated control rats) with site-specific osteolytic bone metastasis of the hind leg were imaged with a 1.5 T clinical MRI-scanner in an animal coil as well as in a volumetric CT-scanner at days 30, 40, 50 and 60 after inoculation of MDA-MB-231 human breast cancer cells. From these data, osteolytic lesion size (OLS), peak enhancement (PE), area under the curve (AUC), amplitude (A), exchange rate constant (k{sub ep}) and apparent diffusion coefficient (ADC) were determined in bone metastases. Prior to changes in OLS (p {<=} 0.05 at days 50 and 60) there was already a significant decrease in PE, AUC and A (p {<=} 0.05 at days 40-60) in treated animals compared to controls. However, for k{sub ep} and ADC there were no significant differences between the groups at any time point (p > 0.05 at days 40-60). In conclusion, anti-angiogenic treatment response in osteolytic breast cancer bone metastases can be assessed early with surrogate markers of vascularization, while DWI appears to be insensitive.

  6. Animal models in peritoneal dialysis

    Science.gov (United States)

    Nikitidou, Olga; Peppa, Vasiliki I.; Leivaditis, Konstantinos; Eleftheriadis, Theodoros; Zarogiannis, Sotirios G.; Liakopoulos, Vassilios

    2015-01-01

    Peritoneal dialysis (PD) has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease (ESRD). In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use. PMID:26388781

  7. Animal Models in Peritoneal Dialysis

    Directory of Open Access Journals (Sweden)

    OLGA eNIKITIDOU

    2015-09-01

    Full Text Available Peritoneal dialysis (PD has been extensively used over the past years as a method of kidney replacement therapy for patients with end stage renal disease. In an attempt to better understand the properties of the peritoneal membrane and the mechanisms involved in major complications associated with PD, such as inflammation, peritonitis and peritoneal injury, both in vivo and ex vivo animal models have been used. The aim of the present review is to briefly describe the animal models that have been used, and comment on the main problems encountered while working with these models. Moreover, the differences characterizing these animal models, as well as, the differences with humans are highlighted. Finally, it is suggested that the use of standardized protocols is a necessity in order to take full advantage of animal models, extrapolate their results in humans, overcome the problems related to PD and help promote its use.

  8. 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.

  9. Animal models for candidiasis.

    Science.gov (United States)

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

    2014-04-02

    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.

  10. Animal Models for Candidiasis

    OpenAIRE

    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.

  11. Animal models of asthma

    OpenAIRE

    Akkoç, Tunç

    2014-01-01

    ABSTRACT: Allergic disease such as asthma, rhinitis, and eczema are increasing prevelanceand affect up to 15% of population in Westernized countries. Among them, asthma is achronic inflammatory disease of airways and the underlying physiological and immunologicalprocesses are not fully understood. Mouse models of asthma dupicates many featuresof human asthma, including airway hyperreactivity, andairway inflammation. Therefore, relevantmodels for asthma are important to understand the mechanis...

  12. Animal Models of Ricin Toxicosis

    OpenAIRE

    Roy, Chad J; Song, Kejing; Sivasubramani, Satheesh K.; Gardner, Donald J.; Seth H Pincus

    2012-01-01

    Animal models of ricin toxicosis are necessary for testing the efficacy of therapeutic measures, as well studying the mechanisms by which ricin exerts its toxicity in intact animals. Because ricin can serve as a particularly well-characterized model of tissue damage, and the host response to that damage, studies of the mechanisms of ricin toxicity may have more general applicability. For example, our studies of the molecular mechanisms underlying the development of ricin-induced hypoglycemia ...

  13. Animal models of anorexia and cachexia

    Science.gov (United States)

    DeBoer, Mark Daniel

    2009-01-01

    Background Cachexia is a devastating syndrome of body wasting that worsens quality of life and survival for patients suffering from diseases such as cancer, chronic kidney disease and chronic heart failure. Successful treatments have been elusive in humans, leaving a clear need for the development of new treatment compounds. Animal models of cachexia are able to recapitulate the clinical findings from human disease and have provided a much-needed means of testing the efficacy of prospective therapies. Objective This review focuses on animal models of cachexia caused by cancer, chronic heart failure and chronic kidney disease, including the features of these models, their implementation, and commonly-followed outcome measures. Conclusion Given a dire clinical need for effective treatments of cachexia, animal models will continue a vital role in assessing the efficacy and safety of potential treatments prior to testing in humans. Also important in the future will be the use of animal models to assess the durability of effect from anti-cachexia treatments and their effect on prognosis of the underlying disease states. PMID:20160874

  14. Animal models of portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Juan G Abraldes; Marcos Pasarín; Juan Carlos; García-Pagán

    2006-01-01

    Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model,depending on the specific objectives of the study, are also discussed.

  15. Animal models in myopia research.

    Science.gov (United States)

    Schaeffel, Frank; Feldkaemper, Marita

    2015-11-01

    Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. PMID:26769177

  16. Multifunctional Polymeric Micelles Co-loaded with Anti-Survivin siRNA and Paclitaxel Overcome Drug Resistance in an Animal Model of Ovarian Cancer.

    Science.gov (United States)

    Salzano, Giuseppina; Navarro, Gemma; Trivedi, Malav S; De Rosa, Giuseppe; Torchilin, Vladimir P

    2015-04-01

    Ovarian cancer is a dreadful disease estimated to be the second most common gynecologic malignancy worldwide. Its current therapy, based on cytoreductive surgery followed by the combination of platinum and taxanes, is frequently complicated by the onset of multidrug resistance (MDR). The discovery that survivin, a small antiapoptotic protein, is involved in chemoresistance provided a new prospect to overcome MDR in cancer, because siRNA could be used to inhibit the expression of survivin in cancer cells. With this in mind, we have developed self-assembly polymeric micelles (PM) able to efficiently co-load an anti-survivin siRNA and a chemotherapeutic agent, such as paclitaxel (PXL; survivin siRNA/PXL PM). Previously, we have successfully demonstrated that the downregulation of survivin by using siRNA-containing PM strongly sensitizes different cancer cells to paclitaxel. Here, we have evaluated the applicability of the developed multifunctional PM in vivo. Changes in survivin expression, therapeutic efficacy, and biologic effects of the nanopreparation were investigated in an animal model of paclitaxel-resistant ovarian cancer. The results obtained in mice xenografed with SKOV3-tr revealed a significant downregulation of survivin expression in tumor tissues together with a potent anticancer activity of survivin siRNA/PXL PM, while the tumors remained unaffected with the same quantity of free paclitaxel. These promising results introduce a novel type of nontoxic and easy-to-obtain nanodevice for the combined therapy of siRNA and anticancer agents in the treatment of chemoresistant tumors. PMID:25657335

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

    OpenAIRE

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

    2016-01-01

    Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocul...

  18. Optogenetics in psychiatric animal models.

    Science.gov (United States)

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

    2013-10-01

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

  19. 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.

  20. 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...

  1. Effects of treatments with angiogenesis inhibitors on tumor stroma in animal experimental models of child cancer Neuroblastoma

    OpenAIRE

    Shiikh Dahir, Mahamed

    2013-01-01

    Neuroblastoma, a neuroendocrine tumor, is the most common cancer in infancy. 75 % of those affected are under the age of 5. The disease is heterogeneous and survival rate is low.   Current treatment of neuroblastoma consists of surgery, radiation and chemotherapy, where the targets for the treatment are the malign cells. Due to the cancer cells instable genome there is a risk for resistance development. This negatively impacts the treatments goal of hindering tumor growth and spread.  Tumor g...

  2. ANIMAL MODELS FOR FOOD ALLERGY

    Science.gov (United States)

    Animal models have been used to provide insight into the complex immunological and pathophysioligical mechanisms of human Type 1 allergic diseases. Research efforts that include mechanistic studies in search of new therapies and screening models for hazard identification of potential allergens in a...

  3. Study on establishment of esophageal carcinoma animal models

    OpenAIRE

    Zhao, Qiang; WEN Danyi; Sun, Jianhe

    2013-01-01

    Esophageal cancer is one of the common human gastrointestinal malignancies.In recent years,the global incidence of esophageal cancer and its mortality rise.China is the high incidence area of esophageal cancer with the highest morbidity and mortality in the world.However,the exact pathogeny of esophageal cancer has not been fully clarified yet.Thus,it is of significant importance to establish ideal and stable esophageal carcinoma animal models with similar biological characteristics to clinic...

  4. 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.

  5. 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.

  6. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

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

    2014-01-01

    , 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...... in non-ideal scenarios, we show that generally the estimation of models of this type is both feasible and ecologically informative. We illustrate the approach using real movement data from 11 reindeer (Rangifer tarandus). Results indicate a directional bias towards a group centroid for reindeer...

  7. Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon;

    superior to rodents as they are more closely related to humans in terms of immunology and physiology. Here, we introduce pigs as a supplementary large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, two tumor...... antigens previously identified as important players in human cancer development and progression, were used as vaccine targets. Using peptide-MHC-I binding predictors we identified IDO-derived and RhoC-derived candidate peptides potentially binding to five different broadly distributed SLA molecules. We...... measured the peptide-SLA complex stability of these and found a total of 89 stable (t½ ≥ 0.5 hours) peptide-MHC complexes with SLA-1*04:01, -1*07:02, -2*04:01, -2*05:02 and/or -3*04:01. For a pilot study, 12 pigs were immunized with overlapping 20-mer peptides spanning the entire IDO and RhoC sequences...

  8. Animal models of CNS disorders.

    Science.gov (United States)

    McGonigle, Paul

    2014-01-01

    There is intense interest in the development and application of animal models of CNS disorders to explore pathology and molecular mechanisms, identify potential biomarkers, and to assess the therapeutic utility, estimate safety margins and establish pharmacodynamic and pharmacokinetic parameters of new chemical entities (NCEs). This is a daunting undertaking, due to the complex and heterogeneous nature of these disorders, the subjective and sometimes contradictory nature of the clinical endpoints and the paucity of information regarding underlying molecular mechanisms. Historically, these models have been invaluable in the discovery of therapeutics for a range of disorders including anxiety, depression, schizophrenia, and Parkinson's disease. Recently, however, they have been increasingly criticized in the wake of numerous clinical trial failures of NCEs with promising preclinical profiles. These failures have resulted from a number of factors including inherent limitations of the models, over-interpretation of preclinical results and the complex nature of clinical trials for CNS disorders. This review discusses the rationale, strengths, weaknesses and predictive validity of the most commonly used models for psychiatric, neurodegenerative and neurological disorders as well as critical factors that affect the variability and reproducibility of these models. It also addresses how progress in molecular genetics and the development of transgenic animals has fundamentally changed the approach to neurodegenerative disorder research. To date, transgenic animal models\\have not been the panacea for drug discovery that many had hoped for. However continual refinement of these models is leading to steady progress with the promise of eventual therapeutic breakthroughs. PMID:23811310

  9. 动物侵袭模型在肿瘤中的相关研究%Animal model of tumor invasion in cancer-related research

    Institute of Scientific and Technical Information of China (English)

    秦林; 岳文涛; 王子彤

    2013-01-01

    肿瘤侵袭模型是研究肿瘤侵袭机制,评价肿瘤防治策略的重要工具.相对于体外模型,体内侵袭模型能更好地模拟肿瘤微环境以及肿瘤侵袭的生物学行为,通过肿瘤的形态学观察和侵袭相关蛋白的检测可以对动物侵袭模型进行评估,现已广泛应用于肿瘤侵袭相关的基础临床研究.%Tumor invasion model is an important tool to study the mechanisms of tumor mvasion and to evaluate prevention and treatment of cancer.Compared to the in vitro model,in vivo model can simulate the tumor microenvironment and tumor mvasion biological behaviour better.Morphological observation and invasion-related protein detection can be used to evaluate the animal invasion model,which are widely used in basic and clinical research now.

  10. Engineered Swine Models of Cancer

    Directory of Open Access Journals (Sweden)

    Adrienne L. Watson

    2016-05-01

    Full Text Available Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications.

  11. Engineered Swine Models of Cancer.

    Science.gov (United States)

    Watson, Adrienne L; Carlson, Daniel F; Largaespada, David A; Hackett, Perry B; Fahrenkrug, Scott C

    2016-01-01

    Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications. PMID:27242889

  12. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  13. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline. PMID:26970137

  14. Animal models of neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Fabiola Mara Ribeiro

    2013-01-01

    Full Text Available The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD and Parkinson's disease (PD, increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

  15. Animal models of source memory.

    Science.gov (United States)

    Crystal, Jonathon D

    2016-01-01

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

  16. ANIMAL BEHAVIORAL MODELS OF TINNITUS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chao; WANG Qiuju; SUN Wei

    2014-01-01

    The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models re-garding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Re-liable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been pro-posed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned re-sponse suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.

  17. 非人灵长类肿瘤模型研究进展%Progress of non-human primate animal models of cancers

    Institute of Scientific and Technical Information of China (English)

    夏厚军; 陈策实

    2011-01-01

    癌症是人类第二大致死的疾病.将体外细胞模型获得的癌症研究结果向临床转化过程中,动物活体实验是必不可少的一个环节.现在的肿瘤活体实验绝大部分采用啮齿类实验动物如小鼠和大鼠,这是因为它们具有个体小、繁殖迅速、遗传背景清楚、转基因技术成熟等优势.但是啮齿类和人的亲缘关系比较远,许多从啮齿类动物模型获得的研究结果不能在人体重现.非人灵长类动物在遗传进化、免疫、生理和代谢等诸多方面与人类高度近似,理论上更加适合癌症研究.本文对现有的非人灵长类肿瘤研究做一综述,主要集中介绍用化学和生物致癌剂在不同的非人灵长类动物诱导肿瘤的研究,为将来用非人灵长类动物研究人类癌症奠定基础.%Cancer is the second leading disease causing human death. Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic. Rodents, including the mouse and rat, have been widely used for pre-clinical studies due to their small size, clear genetic backgrounds, rapid propagation, and mature transgenic technologies. However, because rodents are evolutionarily distinct from humans, many pre-clinical research results using rodent models cannot be reproduced in the clinic. Non-human primates (NHPs) may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution, immune system, physiology and metabolism. This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens. finally, future research directions for the use of NHPs in cancer research are discussed.

  18. Animal Models of Colitis-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Manasa Kanneganti

    2011-01-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC, especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future.

  19. Evaluation of {sup 99m}Tc-glucarate as a breast cancer imaging agent in a xenograft animal model

    Energy Technology Data Exchange (ETDEWEB)

    Gambini, Juan Pablo [Nuclear Medicine Center, Clinical Hospital, University of Uruguay, Montevideo, 11600 (Uruguay); Cabral, Pablo [Nuclear Investigations Center, School of Science, University of Uruguay, Montevideo, 11400 (Uruguay); Alonso, Omar [Nuclear Medicine Center, Clinical Hospital, University of Uruguay, Montevideo, 11600 (Uruguay); Savio, Eduardo [Department of Radiochemistry, School of Chemistry, University of Uruguay, Montevideo, 11800 (Uruguay); Daibes Figueroa, Said [Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States); Zhang Xiuli [Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States); Department of Biochemistry, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri, Columbia, MO 65212 (United States); Deutscher, Susan L. [Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States); Department of Biochemistry, University of Missouri, Columbia, MO 65211 (United States); Quinn, Thomas P., E-mail: quinnt@missouri.ed [Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States); Department of Biochemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65212 (United States)

    2011-02-15

    Introduction: The use of [{sup 99m}Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [{sup 99m}Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [{sup 99m}Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors. Methods: Glucarate in a kit formulation was labeled with {sup 99m}Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [{sup 99m}Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a micro-single photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis and metastatic deposit localization. Results: The Glucarate kits exhibited a stable shelf life of 6 months. [{sup 99m}Tc]Glucarate was obtained with radiochemical purity greater than 95%. Biodistribution studies demonstrated moderate tumor uptake coupled with high renal clearance. Tumor-to-muscle ratios were 4.85 and 5.14 at 1 and 4 h post injection. MRI analysis showed tumors with dense cellular growth and moderate central necrosis. [{sup 99m}Tc]Glucarate uptake in the primary MDA-MB-435 shoulder tumors and metastatic lesions were clearly visualized with micro-SPECT/CT imaging. Conclusions: Selective tumor uptake and rapid clearance from nontarget organs makes [{sup 99m}Tc]glucarate a potential agent for breast cancer imaging that awaits validation in a clinical trial.

  20. Bridging Animal and Human Models

    OpenAIRE

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

    2012-01-01

    Genetics play an important role in the development and course of alcohol abuse, and understanding genetic contributions to this disorder may lead to improved preventative and therapeutic strategies in the future. Studies both in humans and in animal models are necessary to fully understand the neurobiology of alcoholism from the molecular to the cognitive level. By dissecting the complex facets of alcoholism into discrete, well-defined phenotypes that are measurable in both human populations ...

  1. Animal models for microbicide studies

    OpenAIRE

    Veazey, Ronald S.; Shattock, Robin J.; Klasse, Per Johan; Moore, John P.

    2012-01-01

    There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.

  2. Animal models of eating disorders

    OpenAIRE

    Kim, Sangwon F.

    2012-01-01

    Feeding is a fundamental process for basic survival, and is influenced by genetics and environmental stressors. Recent advances in our understanding of behavioral genetics have provided a profound insight on several components regulating eating patterns. However, our understanding of eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating is still poor. The animal model is an essential tool in the investigation of eating behaviors and their pathological forms, yet develop...

  3. Animal Models in Burn Research

    OpenAIRE

    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...

  4. Progesterone receptors - animal models and cell signalling in breast cancer: Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer

    International Nuclear Information System (INIS)

    Progesterone and estradiol, and their nuclear receptors, play essential roles in the physiology of the reproductive tract, the mammary gland and the nervous system. Estrogens have traditionally been considered associated with an increased risk of breast cancer. There is, however, compelling evidence that progesterone plays an important role in breast cell proliferation and cancer. Herein, we review the possible role of progestins and the progesterone receptor-associated signaling pathways in the development of breast cancer, as well as the therapeutic possibilities arising from our growing knowledge of the activation of the progesterone receptor by other proliferative mechanisms

  5. Software Validation via Model Animation

    Science.gov (United States)

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

    2015-01-01

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

  6. 前列腺癌体内实验模型的研究进展%Research progress of in vivo animal models of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    聂迪森; 秦卫军; 温伟红; 赵宁宁; 师长宏

    2015-01-01

    Prostate cancer is one of the most common malignant tumors in men and related studies have achieved great breakthrough in recent years.But because of the lack of effective in vivo animal models, the process to translate basic research into clinical application has been severely hampered.Patient derived prostate tumor xenograft ( PDPTX) model is an ideal animal model in which freshly isolated tumor tissues from patients were inoculated into immunodeficient mice.This model can duplicate the heterogeneity of primary tumor in a better way and keep the tumor complexity at molecular, genetic and pathological levels.Particularly, the PDPTX model, in which the isolated tumor tissue is inoculated under the renal capsule, is even better, because it solves the clrawbacks of traditional subcutaneous inoculation model.In traditional mod-els, the success rate is low, it’s not easy for lower grade tumor to form xenograft, and it’s not easy to reconstruct metasta-sis, etc.PDPTX provides a more ideal in vivo model for prostate cancer studies.It has irreplaceable advantages, especially in target therapy, new drug screening and individualized tumor treatment.%前列腺癌是男性最为常见的恶性肿瘤之一。近年来有关前列腺癌的相关研究取得了较大突破,但由于缺少有效的体内实验模型,导致研究成果向临床应用的转化受到严重阻碍。人源性前列腺癌移植( patient de-rived prostate tumor xenograft,PDPTX)模型是将患者新鲜的肿瘤组织移植于免疫缺陷小鼠而建立的体内模型,该模型能较好地复制原发肿瘤的异质性,保持肿瘤在分子学、基因学和病理学的复杂性。特别是采用肾包膜移植建立PDPTX模型的方法较好地解决了传统皮下移植建模成功率低、低级别肿瘤成瘤难、无法实现移植瘤转移等缺点,为前列腺癌研究提供了更为理想的体内模型。尤其是在靶向治疗、新型药物筛选、个体化治疗等方面具有不可取代的优势。

  7. Engineered Swine Models of Cancer

    OpenAIRE

    Watson, Adrienne L; Carlson, Daniel F.; Largaespada, David A; Hackett, Perry B; Fahrenkrug, Scott C.

    2016-01-01

    Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs...

  8. Animal models of skin regeneration.

    Science.gov (United States)

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kopcewicz, Marta; Kur, Anna

    2014-03-01

    Cutaneous injury in the majority of vertebrate animals results in the formation of a scar in the post-injured area. Scar tissues, although beneficial for maintaining integrity of the post-wounded region often interferes with full recovery of injured tissues. The goal of wound-healing studies is to identify mechanisms to redirect reparative pathways from debilitating scar formation to regenerative pathways that lead to normal functionality. To perform such studies models of regeneration, which are rare in mammals, are required. In this review we discussed skin regenerative capabilities present in lower vertebrates and in models of skin scar-free healing in mammals, e.g. mammalian fetuses. However, we especially focused on the attributes of two unusual models of skin scar-free healing capabilities that occur in adult mammals, that is, those associated with nude, FOXN1-deficient mice and in wild-type African spiny mice.

  9. Evaluation of animal models of neurobehavioral disorders

    OpenAIRE

    Nordquist Rebecca E; Arndt Saskia S; van der Staay F Josef

    2009-01-01

    Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentiall...

  10. An animal model of fetishism.

    Science.gov (United States)

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

    2004-12-01

    An animal model of sexual fetishism was developed with male Japanese quail based on persistence of conditioned sexual responding during extinction to an inanimate object made of terrycloth (Experiments 1 and 3). This persistent responding occurred only in subjects that came to copulate with the terrycloth object, suggesting that the copulatory behavior served to maintain the fetishistic behavior. Sexual conditioning was carried out by pairing a conditioned stimulus (CS) with the opportunity to copulate with a female (the unconditioned stimulus or US). Copulation with the CS object and persistent responding did not develop if the CS was a light (Experiment 1) or if conditioning was carried out with a food US (Experiment 2). In addition, subjects that showed persistence in responding to the terrycloth CS did not persist in their responding to a light CS (Experiment 3). The results are consistent with the hypothesis that conditioned copulatory behavior creates a form of self-maintenance that leads to persistent responding to an inanimate object. The development of an animal model of such fetishistic behavior should facilitate experimental analysis of the phenomenon. PMID:15500813

  11. Animal models and conserved processes

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2012-09-01

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

  12. Animal models of recurrent or bipolar depression.

    Science.gov (United States)

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

    2016-05-01

    Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques. PMID:26265551

  13. Animal models of colorectal cancer and liver metastases%大肠癌肝转移动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨荣娇; 何兴祥

    2009-01-01

    肝脏是大肠癌转移的最常见器官.为更好地研究大肠癌肝转移,建立和选择合适的大肠癌肝转移模型十分重要.在此就大肠癌肝转移模型:原位植入模型,经脾接种癌细胞,门静脉内注射,直接将癌细胞种植到肝脏的相关研究进展进行综述.%The liver is the most common site of distant metastasis of colorectal cancer. In order to study colorectal cancer metastasis to the liver, establishing and choosing appropriate mouse model is crucially im-portant. In this review, we mainly discuss the mouse models of colorectal cancer and liver metastases: Tumor fragments or cancer cells orthotopic transplant to eoloncecal part, injecting cancer cells into the spleen, portal injection of cancer cells, colorectal cancer implantation to the subcapsular of the liver.

  14. Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

    OpenAIRE

    Huang, Liqun; WONG, CHI C.; Mackenzie, Gerardo G; Sun, Yu; Cheng, Ka Wing; Vrankova, Kvetoslava; Alston, Ninche; Ouyang, Nengtai; Rigas, Basil

    2014-01-01

    Background The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). Methods Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic stud...

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

    OpenAIRE

    Keizo Kanasaki; Daisuke Koya

    2011-01-01

    Obesity is an epidemic problem in the world and is associated with several health 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 he...

  16. Animal models of extracranial pediatric solid tumors

    OpenAIRE

    Seitz, Guido; Armeanu-Ebinger, Sorin; WARMANN, STEVEN; Fuchs, Jörg

    2012-01-01

    Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models tha...

  17. How companion animals contribute to the fight against cancer in humans

    Directory of Open Access Journals (Sweden)

    Douglas Thamm, VMD

    2009-03-01

    Full Text Available Companion animals and their human guardians suffer from many of the same types of cancer and are often treated with many of the same drugs. Moreover, the overall tumour biology is much more similar between humans and companion animals than between humans and rodent tumor models. Therefore, it is proposed that pre-clinical evaluation of novel cancer therapeutics should more often include appropriately designed trials in companion animals with cancer to more accurately predict efficacy and toxicity in humans. For example, studies in dogs with cancer have been used to assess efficacy and design human clinical trials of immunotherapy, gene therapy, sustained release drug delivery and liposomal drug delivery. In the future, such studies will ultimately benefit not only humans, but also companion animals with cancer.

  18. The methods of inducing polymyositis animal model

    International Nuclear Information System (INIS)

    Objective: To investigate the methods of inducing polymyosistis(PM) animal model. Methods: In order to develope a induce PM animal model in purified guinea pia muscle myosin mixed with complete Freund adjuvant was injected subcutaneously to SD rats many times and the results of the clinical finding, the EMG, the pathologic changes and the musclar MRI changes in SD rats was assessed. Results: The PM animal models were similar to the human in clinical findings, the EMG, the pathologic changes, the musclar MRI changes and so on. Conclusion: The animal model is similar to the human PM, it is an ideal animal model to investigate PM. (authors)

  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. A Review of Cancer Chemotherapy for Pet Animals

    OpenAIRE

    Norris, A. M.; Withrow, S.J.

    1984-01-01

    A review of the principles of cancer chemotherapy for pet animals is presented. The various pharmacological classes of antineoplastic drugs are described with specific references to those drugs that have been widely used in veterinary medicine.

  1. Animal Models for Vascular Tissue-Engineering

    OpenAIRE

    Swartz, Daniel D.; Andreadis, Stelios T.

    2013-01-01

    Due to rise in cardiovascular disease throughout the world, there is increasing demand for small diameter blood vessels as replacement grafts. The present review focuses on the animal models that have been used to test small-diameter TEVs with emphasis on the attributes of each model. Small animal models are used to test short-term patency and address mechanistic hypotheses; and large, pre-clinical animal models are employed to test long-term patency, remodeling and function in an environment...

  2. Laboratory Animal Models for Brucellosis Research

    Directory of Open Access Journals (Sweden)

    Teane M. A. Silva

    2011-01-01

    Full Text Available Brucellosis is a chronic infectious disease caused by Brucella spp., a Gram-negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated in culture cells and animal models. The mouse is the animal model more commonly used to study chronic infection caused by Brucella. This model is most frequently used to investigate specific pathogenic factors of Brucella spp., to characterize the host immune response, and to evaluate therapeutics and vaccines. Other animal species have been used as models for brucellosis including rats, guinea pigs, and monkeys. This paper discusses the murine and other laboratory animal models for human and animal brucellosis.

  3. 人前列腺癌淋巴转移动物模型的研究进展%Animal models of human prostate cancer lymphatic metastasis:a review

    Institute of Scientific and Technical Information of China (English)

    张树江; 孙祖越

    2016-01-01

    前列腺癌是美国男性人群中最常见的恶性肿瘤,在我国的发病率也呈明显上升趋势。前列腺癌淋巴结转移强烈预示存在远端器官转移并且预后不佳。前列腺癌淋巴转移动物模型可以应用于研究前列腺癌的发病机制和转移机制,并评价前列腺癌淋巴转移潜在新防治措施的有效性。本文综述了常用的人前列腺癌淋巴转移动物模型,包括异种移植小鼠模型、遗传工程小鼠模型、大鼠模型和犬模型,阐述了这些模型的功能、特点、优势和不足,介绍了肿瘤干细胞在此模型中的应用和此模型的常用检测方法,并指出亟待解决的重点问题。%Prostate cancer is the most common cancer among males in the United states,and the incidence has risen dramatically in recent years in China. Lymph node metastasis is a strong predictor of the metastatic potential and poor outcome of prostate cancer. Animal models of human prostate cancer lymphatic metastasis can be used to study the pathogenesis and metastatic mechanisms of prostate cancer,and evaluate the efficacy of new drugs for lymphatic metastasis of prostate cancer. This paper reviews commonly-used animal models of human prostate cancer lymphatic metastasis,including xenograft mouse models,genetically engineered mouse models,rat models and canine models,analyzes their advantages and disadvantages,presents their functions and characteristics,introduces the applications of cancer stem cells in these models and test methods of these models,and highlights the main problems to be solved.

  4. Animal models of tuberculosis for vaccine development.

    Science.gov (United States)

    Gupta, U D; Katoch, V M

    2009-01-01

    Animal models for testing different vaccine candidates have been developed since a long time for studying tuberculosis. Mice, guinea pigs and rabbits are animals most frequently used. Each model has its own merits for studying human tuberculosis, and none completely mimics the human disease. Different animal models are being used depending upon the availability of the space, trained manpower as well as other resources. Efforts should continue to develop a vaccine which can replace/outperform the presently available vaccine BCG. PMID:19287053

  5. Engineering large animal models of human disease

    OpenAIRE

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

    2015-01-01

    Abstract The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site‐specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of...

  6. Experimental Animal Models in Periodontology: A Review

    OpenAIRE

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

    2010-01-01

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and pr...

  7. Evaluation of spinal cord injury animal models

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  8. Animal models of polymicrobial pneumonia

    OpenAIRE

    Hraiech S; Papazian L.; Rolain JM; Bregeon F

    2015-01-01

    Sami Hraiech,1,2 Laurent Papazian,1,2 Jean-Marc Rolain,1 Fabienne Bregeon1,3IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France; 2Réanimation – Détresses respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France; 3Service d’Explorations Fonctionnelles Respiratoires, APHM, CHU Nord, Marseille, FranceAbstract: Pneumonia is one of the leading causes of severe and occasion...

  9. Limitations of Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    J. A. Potashkin

    2011-01-01

    Full Text Available Most cases of Parkinson's disease (PD are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of the disease and provide a means for testing new treatments. However, the current animal models often fall short in replicating the true pathophysiology occurring in idiopathic PD, and thus results from animal models often do not translate to the clinic. In this paper we will explain the limitations of animal models of PD and why their use is inappropriate for the study of some aspects of PD.

  10. A REVIEW ON ANIMAL MODELS OF DEPRESSION

    OpenAIRE

    Madhu Devi* and Ramica Sharma

    2013-01-01

    As described by the world health organization (WHO), depression is the most common and serious disorder leading to suicide. Numbers of synthetic drugs are available for the treatment of this fatal disease, but are associated with serious complications. A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models. The number of validated animal models for affective diso...

  11. Animal Models in Studying Cerebral Arteriovenous Malformation

    Directory of Open Access Journals (Sweden)

    Ming Xu

    2015-01-01

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

  12. Animal Models in Studying Cerebral Arteriovenous Malformation

    OpenAIRE

    Ming Xu; Hongzhi Xu; Zhiyong Qin

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal ...

  13. A Brief History of Animal Modeling

    OpenAIRE

    Ericsson, Aaron C.; Crim, Marcus J; Franklin, Craig L.

    2013-01-01

    Comparative medicine is founded on the concept that other animal species share physiological, behavioral, or other characteristics with humans. Over 2,400 years ago it was recognized that by studying animals, we could learn much about ourselves. This technique has now developed to the point that animal models are employed in virtually all fields of biomedical research including, but not limited to, basic biology, immunology and infectious disease, oncology, and behavior.

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

    Directory of Open Access Journals (Sweden)

    Marta M. Stei

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Development of osteoporosis animal model using micropigs

    OpenAIRE

    Kim, Sang-Woo; Kim, Kyoung-Shim; Solis, Chester D.; Lee, Myeong-Seop; Hyun, Byung-Hwa

    2013-01-01

    Osteoporosis is a known major health problem and a serious disease of the bone, there has been a great need to develop more and newer animal models for this disease. Among animal models used for testing drug efficacy, the minipig model has become useful and effective due to its close similarity with humans (validity), particularly with the pharmacokinetics of compounds via subcutaneous administration, the structure and function of the organs, the morphology of bone and the overall metabolic n...

  18. 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

  19. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

    3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea

  20. Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis

    OpenAIRE

    Kodama, Masaaki; Murakami, Kazunari; Sato, Ryugo; Okimoto, Tadayoshi; Nishizono, Akira; Fujioka, Toshio

    2005-01-01

    Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (H pylori), several animal models with H pylori infection have been developed to confirm the association between H pylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation...

  1. Animal Models for the Study of Osteomyelitis

    OpenAIRE

    Patel, Mitul; Rojavin, Yuri; Jamali, Amir A.; Wasielewski, Samantha J.; Salgado, Christopher J.

    2009-01-01

    Osteomyelitis is an acute or chronic inflammatory process of the bone and its related structures secondary to an infection with pyogenic organisms. Because of the variety in disease presentations and pathophysiology of osteomyelitis, it is very difficult to evaluate in clinical studies. Therefore, animal models have been created for in vivo experimentation. A PubMed and OVID search was performed on March 31, 2008, using keywords osteomyelitis, animal model (rabbit, rat, mouse, avian, dog, she...

  2. Animal models of osteoporosis - necessity and limitations

    OpenAIRE

    Turner A. Simon

    2001-01-01

    There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep ar...

  3. Animal Models of Stress Urinary Incontinence

    OpenAIRE

    Jiang, Hai-Hong; Damaser, Margot S.

    2011-01-01

    Stress urinary incontinence (SUI) is a common health problem significantly affecting the quality of life of women worldwide. Animal models that simulate SUI enable the assessment of the mechanism of risk factors for SUI in a controlled fashion, including childbirth injuries, and enable preclinical testing of new treatments and therapies for SUI. Animal models that simulate childbirth are presently being utilized to determine the mechanisms of the maternal injuries of childbirth that lead to S...

  4. A cognitive model's view of animal cognition

    OpenAIRE

    Sidney D'MELLO, Stan FRANKLIN

    2011-01-01

    Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework c...

  5. Limitations of Animal Models of Parkinson's Disease

    OpenAIRE

    J. A. Potashkin; Blume, S. R.; Runkle, N. K.

    2011-01-01

    Most cases of Parkinson's disease (PD) are sporadic. When choosing an animal model for idiopathic PD, one must consider the extent of similarity or divergence between the physiology, anatomy, behavior, and regulation of gene expression between humans and the animal. Rodents and nonhuman primates are used most frequently in PD research because when a Parkinsonian state is induced, they mimic many aspects of idiopathic PD. These models have been useful in our understanding of the etiology of t...

  6. Use of animal models in musculoskeletal research.

    OpenAIRE

    Neyt, J. G.; Buckwalter, J. A.; Carroll, N. C.

    1998-01-01

    Understanding of the human musculoskeletal system and common clinical disorders of bones, joints and soft tissues has been enhanced by the use of experimental animal models. Articles reporting on the results of these biomedical experiments frequently include conclusions that are based on the assumption that the biology of the animal model is similar to that of a human being for the disease process under investigation. The purpose of this investigation was to study the criteria and the conside...

  7. Animal models for the study of tendinopathy

    OpenAIRE

    Warden, S. J.

    2006-01-01

    Tendinopathy is a common and significant clinical problem characterised by activity‐related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent po...

  8. Progress in animal models for predicting the results of clinical trials of cancer drugs%预测肿瘤药物临床试验效果的动物模型新进展

    Institute of Scientific and Technical Information of China (English)

    余飞; 丁慧

    2015-01-01

    基于人体试验的实际应用及伦理方面的考虑,合适的动物模型对于肿瘤药物研发至关重要。制药公司和研究机构在肿瘤治疗新药的开发过程中消耗大量资源,最佳动物体内模型的选择可以改进或缩短研发进程。在技术复杂性方面,肿瘤遗传工程小鼠模型( GEMM)已逐步完善,并且GEMM能够准确重建人类肿瘤的同源发生,为加快肿瘤药物的开发提供机遇。本文主要综合比较预测肿瘤药物临床试验效果的不同类型动物模型,探讨其优劣,并对体内模型的评估方法及与临床转化等进行简述,为肿瘤药物临床前试验提供参考。%Due to practical and ethical concerns associated with human experiments, animal models have been essential in cancer research.Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process.Genetically engineered mouse models ( GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have provided opportunities to accelerate the development of cancer drugs.In this article we consider the different types of animal models used for predicting the results of clinical trials of cancer drugs, and discuss the strengths and weaknesses of each in this regard.In addition, the methods of predicting in vivo models and clinical translation are discussed.

  9. A cognitive model's view of animal cognition

    Directory of Open Access Journals (Sweden)

    Sidney D'MELLO, Stan FRANKLIN

    2011-08-01

    Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].

  10. 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.

  11. Progress With Nonhuman Animal Models of Addiction.

    Science.gov (United States)

    Crabbe, John C

    2016-09-01

    Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten. PMID:27588527

  12. Animal models in motion sickness research

    Science.gov (United States)

    Daunton, Nancy G.

    1990-01-01

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

  13. Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

    International Nuclear Information System (INIS)

    The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic studies were also carried out to elucidate the mechanism of action of PA-2. PA-2 inhibited the growth of TNBC cells in vitro more potently than aspirin. Treatment of established subcutaneous TNBC xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2, but not aspirin, significantly prevented the development of orthotopic MDA-MB-231 xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation of epidermal growth factor receptor (EGFR) and suppressed its downstream signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of p53 at multiple lysine residues and enhanced its DNA binding activity, leading to cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin system, consequently inhibiting the activation of the redox sensitive transcription factor NF-κB. These molecular alterations were observed in vitro and in vivo, demonstrating their relevance to the anticancer effect of PA-2. Our findings demonstrate that PA-2 possesses potent chemotherapeutic efficacy against TNBC, and is also effective in its chemoprevention, warranting further evaluation as an anticancer agent

  14. 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...

  15. Design principles of interactive animated models for electronic learning tools

    OpenAIRE

    Дайняк, И. В.; Баев, В. С.; Карпович, С. Е.

    2013-01-01

    The design principles of interactive animated models for multimedia representation of educational materials were described. The interface of animated model was presented; it consists of header, border, scene, text message area, animation control panel, list of episodes. The animation effects for the applying to animated objects were developed, and templates of animated models were presented.

  16. Animal models of anxiety disorders and stress

    OpenAIRE

    Campos, Alline C; Manoela V. Fogaca; Daniele C. Aguiar; Guimaraes, Francisco S.

    2013-01-01

    Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents). The development of animal models of anxiety and stress has helped to identify the pharmacological mecha...

  17. Animal models of contraception: utility and limitations

    OpenAIRE

    Liechty ER; Bergin IL; Bell JD

    2015-01-01

    Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic co...

  18. Animal models of contraception: utility and limitations

    OpenAIRE

    Bell, Jason

    2015-01-01

    Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologi...

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

    Science.gov (United States)

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

    1990-01-01

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

  20. 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.

  1. Animal and cellular models of human disease

    OpenAIRE

    Arends, Mark; White, Eric; Whitelaw, Christopher

    2016-01-01

    In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

  2. 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.

  3. Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Allen, N.E.; Key, T.J.; Appleby, P.N.; Travis, R.C.; Roddam, A.W.; Tjonneland, A.; Johnsen, N.F.; Overvad, K.; Linseisen, J.; Rohrmann, S.; Boeing, H.; Pischon, T.; Bueno-De-Mesquita, H.B.; Kiemeney, L.; Tagliabue, G.; Palli, D.; Vineis, P.; Tumino, R.; Trichopoulou, A.; Kassapa, C.; Trichopoulos, D.; Ardanaz, E.; Larranaga, N.; Tormo, M.J.; Gonzalez, C.A.; Quiros, J.R.; Sanchez, M.J.; Bingham, S.; Khaw, K.T.; Manjer, J.; Berglund, G.; Stattin, P.; Hallmans, G.; Slimani, N.; Ferrari, P.; Rinaldi, S.; Riboli, E.

    2008-01-01

    We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight

  4. Animal foods, protein, calcium and prostate cancer risk : the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Allen, N. E.; Key, T. J.; Appleby, P. N.; Travis, R. C.; Roddam, A. W.; Tjonneland, A.; Johnsen, N. F.; Overvad, K.; Linseisen, J.; Rohrmann, S.; Boeing, H.; Pischon, T.; Bueno-de-Mesquita, H. B.; Kiemeney, L.; Tagliabue, G.; Palli, D.; Vineis, P.; Tumino, R.; Trichopoulou, A.; Kassapa, C.; Trichopoulos, D.; Ardanaz, E.; Larranaga, N.; Tormo, M-J; Gonzalez, C. A.; Quiros, J. R.; Sanchez, M-J; Bingham, S.; Khaw, K-T; Manjer, J.; Berglund, G.; Stattin, P.; Hallmans, G.; Slimani, N.; Ferrari, P.; Rinaldi, S.; Riboli, E.

    2008-01-01

    We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight

  5. Animal models for Gaucher disease research

    Directory of Open Access Journals (Sweden)

    Tamar Farfel-Becker

    2011-11-01

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

  6. Differential Paradigms in Animal Models of Sepsis.

    Science.gov (United States)

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2016-09-01

    Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis. PMID:27432263

  7. 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...... of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted...... toward the therapeutic efficacy of drug interventions....

  8. Animal models of focal brain ischemia

    OpenAIRE

    Sicard Kenneth M; Fisher Marc

    2009-01-01

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

  9. Novel Animal Models of Pediatric Epilepsy

    OpenAIRE

    Auvin, Stéphane; Pineda, Eduardo; Shin, Don; Gressens, Pierre; Mazarati, Andrey

    2012-01-01

    When mimicking epileptic processes in a laboratory setting, it is important to understand the differences between experimental models of seizures and epilepsy. Because human epilepsy is defined by the appearance of multiple spontaneous recurrent seizures, the induction of a single acute seizure without recurrence does not constitute an adequate epilepsy model. Animal models of epilepsy might be useful for various tasks. They allow for the investigation of pathophysiological mechanisms of the ...

  10. Animal models of skin disease for drug discovery

    Science.gov (United States)

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-01-01

    Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893

  11. Animal models of gene-nutrient interactions.

    Science.gov (United States)

    Reed, Danielle R

    2008-12-01

    Food intake of humans is governed by the food's nutritional value and pleasing taste, but also by other factors such as food cost and availability, cultural imperatives, and social status. The biological determinants of human food intake are not easily parsed from these other factors, making them hard to study against the whirligig aspects of human life in a modern age. The study of animals provides a useful alternative. Humans have a history of studying animal food intake, for agricultural reasons (e.g., pigs and cows), and for personal reasons (e.g., dogs and cats), and these practical concerns have been joined with the appreciation that other models can teach us the principles of behavior, genetics, and nutrition. Thus there is a steady use of the traditional animal models in this type of research, as well as growth in the use of other systems such as worms and flies. Rats and mice occupy a special niche as animal models for two reasons; first, they share with humans a love of the same types of food, and second, they are the target of a number of well-developed genetic tools. The available genetic tools that make mice a popular model include a well-annotated genome (Mouse Build 37), profiles of RNA expression from many tissues, a diverse panel of inbred strains, and the ability to manipulate genes in the whole animal, including removing a gene only in specific tissues (e.g., Cre-lox system). Mice have been harnessed to find genotypes that contribute to sweet-liking, and other studies are underway to understand how genetic variation might at least partially explain other puzzles of human appetites. Animal models provide a way to study the genetic determinants of food selection with experimental rigor and therefore complement human genetics studies. PMID:19037208

  12. Animal models for studying penile hemodynamics

    Institute of Scientific and Technical Information of China (English)

    HiroyaMizusawa; OsamuIshizuka

    2002-01-01

    Animal models for the study of erectile function monitoring the changes in intracavernous pressure(ICP)during penile erection was reviewed.The development of new modwls using small commercially-available experimen-tal animals,rats and mice,in the last edcade facilitated in vivo investigation of erectile physiology.The technique enabled to evaluate even subtle erectile responses by analyzing ICPand systemic blood pressure,Moreover,the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection.Also,more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICPstudies in rats and mice.

  13. Gastric cancer: Animal studies on the risk of hypoacidity and hypergastrinemia

    Institute of Scientific and Technical Information of China (English)

    Reidar Fossmark; Gunnar Qvigstad; Helge L Waldum

    2008-01-01

    Gastric hypoacidity and hypergastrinaemia are seen in several conditions associated with an increased risk of gastric malignancy. Hypoacidity and hypergastrinaemia are closely related and their long-term effects are difficult to study separately in patients. Studies using animal models can provide valuable information about risk factors and mechanisms in gastric cancer development as the models allow a high degree of intervention when introducing or eliminating factors possibly affecting carcinogenesis. In this report, we briefly review findings from relevant animal studies on this topic. Animal models of gastric hypoacidity and hypergastrinaemia provide evidence hypergastrinaemia is a common causative factor in many otherwise diverse settings. In all species where sufficient hypoacidity and hypergastrinaemia have been induced, a proportion of the animals develop malignant lesions in the gastric oxyntic mucosa.

  14. Animal Models of Middle Ear Cholesteatoma

    OpenAIRE

    Tomomi Yamamoto-Fukuda; Haruo Takahashi; Takehiko Koji

    2011-01-01

    Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have b...

  15. 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...

  16. 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.

  17. Animal models for genetic neuromuscular diseases.

    Science.gov (United States)

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

    2008-03-01

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

  18. Animal models for meniscus repair and regeneration.

    Science.gov (United States)

    Deponti, Daniela; Di Giancamillo, Alessia; Scotti, Celeste; Peretti, Giuseppe M; Martin, Ivan

    2015-05-01

    The meniscus plays an important role in knee function and mechanics. Meniscal lesions, however, are common phenomena and this tissue is not able to achieve spontaneous successful repair, particularly in the inner avascular zone. Several animal models have been studied and proposed for testing different reparative approaches, as well as for studying regenerative methods aiming to restore the original shape and function of this structure. This review summarizes the gross anatomy, function, ultrastructure and biochemical composition of the knee meniscus in several animal models in comparison with the human meniscus. The relevance of the models is discussed from the point of view of basic research as well as of clinical translation for meniscal repair, substitution and regeneration. Finally, the advantages and disadvantages of each model for various research directions are critically discussed. PMID:23712959

  19. Animal Models of Human Granulocyte Diseases

    OpenAIRE

    Schäffer, Alejandro A.; Klein, Christoph

    2012-01-01

    In vivo animal models have proven very useful to understand basic biological pathways of the immune system, a prerequisite for the development of innovate therapies. This manuscript addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve di...

  20. Animal Models of Calcific Aortic Valve Disease

    OpenAIRE

    Sider, Krista L.; Blaser, Mark C.; Simmons, Craig A.

    2011-01-01

    Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the u...

  1. Animal Models of Dengue Virus Infection

    OpenAIRE

    Eva Harris; Simona Zompi

    2012-01-01

    The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe deng...

  2. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    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 ...

  3. Update on Animal Models for HIV Research

    OpenAIRE

    Haigwood, Nancy L.

    2009-01-01

    Animal models for HIV research have been indispensible in fulfilling Koch’s postulate and in exploring issues of viral infectivity and pathogenesis, sequence divergence, route(s) of acquisition, tissue distribution and tropism, immunogenicity and protection capacity of vaccine candidates, escape from adaptive immunity, and more. Did they fail to predict the efficacy of T cell vaccines in humans? This article summarizes progress and status of models to inform and complement clinical work.

  4. High Resolution X-ray Computed Tomography: An Emerging Tool for Small Animal Cancer Research

    Directory of Open Access Journals (Sweden)

    Michael J. Paulus

    2000-01-01

    Full Text Available Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for cancer research. These new imaging systems permit researchers to noninvasively screen animals for mutations or pathologies and to monitor disease progression and response to therapy. One imaging modality, X-ray microcomputed tomography (microCT shows promise as a cost-effective means for detecting and characterizing soft-tissue structures, skeletal abnormalities, and tumors in live animals. MicroCT systems provide highresolution images (typically 50 microns or less, rapid data acquisition (typically 5 to 30 minutes, excellent sensitivity to skeletal tissue and good sensitivity to soft tissue, particularly when contrast-enhancing media are employed. The development of microCT technology for small animal imaging is reviewed, and key considerations for designing small animal microCT imaging protocols are summarized. Recent studies on mouse prostate, lung and bone tumor models are overviewed.

  5. Evaluation of surrogate animal models of melioidosis

    Directory of Open Access Journals (Sweden)

    Jonathan Mark Warawa

    2010-12-01

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

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

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research. PMID:25063426

  7. Animal models of antimuscle specific kinase myasthenia

    Science.gov (United States)

    Richman, David P.; Nishi, Kayoko; Ferns, Michael J.; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A.; Agius, Mark A.

    2014-01-01

    Antimuscle specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance. PMID:23252909

  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 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...

  10. Animal models for diseases of respiratory system

    Directory of Open Access Journals (Sweden)

    R. Adil

    2012-07-01

    Full Text Available Latest trends in understanding of respiratory diseases in human beings can be derived from thorough clinical studies of these diseases occurring in man, but conducting such studies in man is difficult in terms of experimental manipulation. In the last 2 decades, various types of experimental respiratory disease models has been developed and utilized by investigators, which have contributed a lot to the understanding of respiratory diseases in man, but only little investigation has been done on the naturally occurring pulmonary diseases of animals as potential models which could have added to our knowledge. There are certain selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma.

  11. Effects of Animal Venoms and Toxins on Hallmarks of Cancer.

    Science.gov (United States)

    Chaisakul, Janeyuth; Hodgson, Wayne C; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  12. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    Science.gov (United States)

    Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  13. Animal models of anxiety disorders and stress

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2013-01-01

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

  14. 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.

  15. Towards an animal model of food addiction.

    Science.gov (United States)

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

    2012-01-01

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

  16. Animal models of epilepsy: use and limitations

    Directory of Open Access Journals (Sweden)

    Kandratavicius L

    2014-09-01

    Full Text Available Ludmyla Kandratavicius,1 Priscila Alves Balista,1 Cleiton Lopes-Aguiar,1 Rafael Naime Ruggiero,1 Eduardo Henrique Umeoka,2 Norberto Garcia-Cairasco,2 Lezio Soares Bueno-Junior,1 Joao Pereira Leite11Department of Neurosciences and Behavior, 2Department of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, BrazilAbstract: Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research.Keywords: epilepsy, animal model, pilocarpine, kindling, neurodevelopment

  17. Progesterone receptors – animal models and cell signaling in breast cancer: The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis

    International Nuclear Information System (INIS)

    A relatively small number of cells in the normal human mammary gland express receptors for oestrogen and progesterone (ER and PR), and there is almost complete dissociation between steroid receptor expression and proliferation. Increased expression of the ER alpha (ERα) and loss of the inverse relationship between receptor expression and proliferation occur at the very earliest stages of tumorigenesis, implying that dysregulation of ERα expression contributes to breast tumour formation. There is evidence also for alterations in the ratio between the two PR isoforms in premalignant breast lesions. Elucidation of the factors mediating the effects of oestradiol and progesterone on development of the normal breast and of the mechanisms by which expression of the ERα and the PR isoforms is controlled could identify new targets for breast cancer prevention and improved prediction of breast cancer risk

  18. Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

    Science.gov (United States)

    Hoffman, Andrew M; Dow, Steven W

    2016-07-01

    Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. PMID:27066769

  19. 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...

  20. Experimental Diabetes Mellitus in Different Animal Models.

    Science.gov (United States)

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

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. PMID:27595114

  1. Penile autotransplantation in rats: An animal model

    OpenAIRE

    Seyam, Raouf M.; Said A Kattan; Assad, Lina W.; Raafat M El-Sayed; Falah H Almohanna

    2013-01-01

    Context: Penile allotransplantation might be a viable option for patients who need penile reconstruction. Aims: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. Settings and Design: Experimental animal study. Materials and Methods: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification o...

  2. Animal models of human herpesvirus 6 infection

    OpenAIRE

    Joséphine eReynaud; Branka eHorvat

    2013-01-01

    Human herpesvirus (HHV)-6A and HHV-6B are two enveloped DNA viruses of β-herpesvirus family, infecting over 90% of the population and associated with several diseases, including exanthema subitum (for HHV-6B), multiple sclerosis and encephalitis, particularly in immunosuppressed patients. Animal models are highly important to better understand the pathogenesis of viral infections. Naturally developed neutralizing antibodies to HHV-6 or a related virus were found in different species of monkey...

  3. Animal models for Gaucher disease research

    OpenAIRE

    Tamar Farfel-Becker; 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...

  4. Diabetic Retinopathy: Animal Models, Therapies, and Perspectives

    Directory of Open Access Journals (Sweden)

    Xue Cai

    2016-01-01

    Full Text Available Diabetic retinopathy (DR is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment are discussed.

  5. Evaluation of Surrogate Animal Models of Melioidosis

    OpenAIRE

    Warawa, Jonathan Mark

    2010-01-01

    Burkholderia pseudomallei is the Gram-negative bacterial pathogen responsible for the disease melioidosis. B. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. B. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant...

  6. Large animal models for stem cell therapy

    OpenAIRE

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

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  7. The wobbler mouse, an ALS animal model

    OpenAIRE

    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 similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now,...

  8. Animal Models of Typical Heterotopic Ossification

    OpenAIRE

    Lixin Kan; Kessler, John A.

    2010-01-01

    Heterotopic ossification (HO) is the formation of marrow-containing bone outside of the normal skeleton. Acquired HO following traumatic events is a common and costly clinical complication. In contrast, hereditary HO is rarer, progressive, and life-threatening. Substantial effort has been directed towards understanding the mechanisms underlying HO and finding efficient treatments. However, one crucial limiting factor has been the lack of relevant animal models. This article reviews the major ...

  9. Mouse models of anemia of cancer.

    Directory of Open Access Journals (Sweden)

    Airie Kim

    Full Text Available Anemia of cancer (AC may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI, with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.

  10. Animal Models of Compulsive Eating Behavior

    Directory of Open Access Journals (Sweden)

    Matteo Di Segni

    2014-10-01

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

  11. Animal Models of Varicella Zoster Virus Infection

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2013-05-01

    Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (chickenpox followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles. HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella and Zostavax® (for HZ. Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection.

  12. Neuroteratology and Animal Modeling of Brain Disorders.

    Science.gov (United States)

    Archer, Trevor; Kostrzewa, Richard M

    2016-01-01

    Over the past 60 years, a large number of selective neurotoxins were discovered and developed, making it possible to animal-model a broad range of human neuropsychiatric and neurodevelopmental disorders. In this paper, we highlight those neurotoxins that are most commonly used as neuroteratologic agents, to either produce lifelong destruction of neurons of a particular phenotype, or a group of neurons linked by a specific class of transporter proteins (i.e., dopamine transporter) or body of receptors for a specific neurotransmitter (i.e., NMDA class of glutamate receptors). Actions of a range of neurotoxins are described: 6-hydroxydopamine (6-OHDA), 6-hydroxydopa, DSP-4, MPTP, methamphetamine, IgG-saporin, domoate, NMDA receptor antagonists, and valproate. Their neuroteratologic features are outlined, as well as those of nerve growth factor, epidermal growth factor, and that of stress. The value of each of these neurotoxins in animal modeling of human neurologic, neurodegenerative, and neuropsychiatric disorders is discussed in terms of the respective value as well as limitations of the derived animal model. Neuroteratologic agents have proven to be of immense importance for understanding how associated neural systems in human neural disorders may be better targeted by new therapeutic agents. PMID:26857462

  13. Animal models of compulsive eating behavior.

    Science.gov (United States)

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

    2014-10-01

    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-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies. PMID:25340369

  14. Animal models in drug development for MRSA.

    Science.gov (United States)

    Marra, Andrea

    2014-01-01

    One of the foremost challenges of drug discovery in any therapeutic area is that of solidifying the correlation between in vitro activity and clinical efficacy. Between these is the confirmation that affecting a particular target in vivo will lead to a therapeutic benefit. In antibacterial drug discovery, there is a key advantage from the start, since the targets are bacteria-therefore, it is simple to ascertain in vitro whether a drug has the desired effect, i.e., bacterial cell inhibition or killing, and to understand the mechanism by which that occurs. The downstream criteria, whether a compound reaches the infection site and achieves appropriately high levels to affect bacterial viability, can be evaluated in animal models of infection. In this way animal models of infection can be a highly valuable and predictive bridge between in vitro drug discovery and early clinical evaluation.The Gram-positive pathogen Staphylococcus aureus causes a wide variety of infections in humans (Archer, Clin Infect Dis 26:1179-1181, 1998) and has been said to be able to infect every tissue type. Fortunately, over the years a great deal of effort has been expended toward developing infection models in rodents using this organism, with good success. This chapter will describe the advantages, methods, and outcome measurements of the rodent models most used in drug discovery for S. aureus. Mouse models will be the focus of this chapter, as they are the most economical and thus most commonly used, but a rat infection model is included as well.

  15. Proliferative retinopathies: animal models and therapeutic opportunities.

    Science.gov (United States)

    Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima

    2015-01-01

    Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders. PMID:25760215

  16. Role of papillomavirus oncogenes in human cervical cancer: Transgenic animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Griep, A.E.; Lambert, P.F. [Univ. of Wisconsin School of Medicine, Madison, WI (United States)

    1994-05-01

    Human papillomaviruses are believed to be etiologic agents for the majority of human cervical carcinoma, a common cancer that is a leading cause of death by cancer among women worldwide. In cervical carcinoma, a subset of papillomaviral genes, namely E6 and E7, are expressed. In vitro tissue culture studies indicate that HPV E6 and E7 are oncogenes, and that their oncogenicity is due in part to their capacity to inactivate cellular tumor suppressor genes. The behavior of E6 and E7 in vitro and the genetic evidence from analysis of human cancers suggest that the E6 and E7 genes play a significant role in the development of cervical cancer. This hypothesis is now being tested using animal models. In this review, we summarize our current knowledge of the oncogenicity of papillomavirus genes that has been generated through their study in transgenic mice. 82 refs., 4 figs., 1 tab.

  17. Animating Event B Models by Formal Data Models

    Science.gov (United States)

    Ait-Sadoune, Idir; Ait-Ameur, Yamine

    We present a formal approach allowing to animate event B formal models. Invariants, deadlock freeness properties are expressed and proved on these models. This paper presents an approach that suggests to complete the proof activity in the event B method by animation activity. The obtained animator may be used to check if the event B models obtained fulfill user requirements, or to provide a help to the developer when describing its formal event B models and particularly in defining event B invariants and guards. More precisely, event B models are translated into data models expressed in the EXPRESS formal data modeling technique. The obtained data models are instantiated and provide an animation of the original B models. Following this approach, it becomes possible to trigger event B models, which themselves trigger entity instantiation on the EXPRESS side. As a further step, we show that the B models can be used as a monitoring system raising alarms in case of incorrect systems behavior. The proposed approach is operationally implemented in the B2EXPRESS tool which handles animation of event B models. It has been experimented for the validation of multimodal human interfaces in the context of VERBATIM project.

  18. Mouse models of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler

    2011-01-01

    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  19. Physically based modeling and animation of tornado

    Institute of Scientific and Technical Information of China (English)

    LIU Shi-guang; WANG Zhang-ye; GONG Zheng; CHEN Fei-fei; PENG Qun-sheng

    2006-01-01

    Realistic modeling and rendering of dynamic tornado scene is recognized as a challenging task for researchers of computer graphics. In this paper a new physically based method for simulating and animating tornado scene is presented. We first propose a Two-Fluid model based on the physical theory of tornado, then we simulate the flow of tornado and its interaction with surrounding objects such as debris, etc. Taking the scattering and absorption of light by the participating media into account, the illumination effects of the tornado scene can be generated realistically. With the support of graphics hardware, various kinds of dynamic tornado scenes can be rendered at interactive rates.

  20. Animal Models Utilized in HTLV-1 Research

    OpenAIRE

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

    2013-01-01

    Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1) over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP). Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examinin...

  1. Clinical relevance of animal models of schizophrenia.

    Science.gov (United States)

    Koch, Michael

    2013-01-01

    Animal models and endophenotypes of mental disorders are regarded as preclinical heuristic approaches aiming at understanding the etiopathogenesis of these diseases, and at developing drug treatment strategies. A frequently used translational model of sensorimotor gating and its deficits in some neuropsychiatric disorders is prepulse inhibition (PPI) of startle. PPI is reduced in schizophrenia patients, but the exact relationship between symptoms and reduced PPI is still unclear. Recent findings suggest that the levels of PPI in humans and animals may be predictive of certain cognitive functions. Hence, this simple measure of reflex suppression may be of use for clinical research. PPI is the reduction of the acoustic startle response that occurs when a weak prestimulus is presented shortly prior to a startling noise pulse. It is considered a measure of sensorimotor gating and is regulated by a cortico-limbic striato-pallidal circuit. However, PPI does not only occur in the domain of startle. PPI of alpha, gamma, and theta oscillations at frontal and central locations has been found, suggesting a relationship between PPI and cognitive processes. In fact, levels of PPI in healthy subjects and in animals predict their performance in cognitive tasks mainly mediated by the frontal cortex. Taken together, PPI might reflect a more general filtering performance leading to gating of intrusive sensory, motor, and cognitive input, thereby improving cognitive function. Hence, PPI might be used in clinical settings to predict the impact of drugs or psychotherapy on cognitive performance in neuropsychiatric patients. PMID:24053035

  2. Animal models of depression: are there any?

    Science.gov (United States)

    O'Neil, Michael F; Moore, Nicholas A

    2003-06-01

    Simple tests for antidepressant-like activity, such as 5-HTP-induced syndrome or reserpine-induced hypomotility, are often mechanism-based tests, pharmacologically specific for certain known classes of therapeutically successful antidepressant agents. Many of these behavioural assays have been superseded by neurochemical techniques such as in vivo microdialysis. In contrast to these mechanistic-based models, investigators have also endeavoured to reproduce in the laboratory, factors that are believed to precipitate depression in people. It is a strong assumption in this approach that depression is a response to stress. This strategy profiles the consequences of chronic stress particularly psychosocial stress or early life events, in order to reproduce in animals the behavioural signs and pathologies associated with depression. The advances in the social psychological, clinical pathological and new areas such as neuroimaging research offer the possibility of establishing more sophisticated models for depression in animals with a broader range of biomarkers from the immunological and endocrinological to neurochemical and behavioural. Combining these novel insights with more traditional tests of depression may not only increase our understanding of the neurobiology of depression but also afford more precise and predictive preclinical models of depression. The responsiveness of different strains or genetically modified animals to stress is likely to be a key area of study. Furthermore we must look to individual differences in subjects, even within the same strain, to more fully understand why some individuals show pathological responses to stress whereas others appear unaffected. Conversely in validating our models using currently available treatments we must include the concept of non-responders so as not to disregard models that may extend therapeutic possibilities in these patients. PMID:12766928

  3. Animal models of craving for ethanol.

    Science.gov (United States)

    Koob, G F

    2000-08-01

    Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving. PMID:11002904

  4. 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...... similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now, 57 years after the first report on the wobbler mouse we summarize the progress made in understanding...

  5. 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.

  6. Experimental animal data and modeling of late somatic effects

    International Nuclear Information System (INIS)

    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. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  8. Animal models in obesity and hypertension.

    Science.gov (United States)

    Segal-Lieberman, Gabriella; Rosenthal, Talma

    2013-06-01

    Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

  9. Animal Models of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Eva Harris

    2012-01-01

    Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.

  10. Melittin restores proteasome function in an animal model of ALS

    Directory of Open Access Journals (Sweden)

    Lee Sang Min

    2011-06-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1 in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation. Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects. The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36 acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice. Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.

  11. Animal models for investigating chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Aghdassi Alexander A

    2011-12-01

    Full Text Available Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.

  12. Animal models for investigating chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Alexander A; Mayerle, Julia; Christochowitz, Sandra; Weiss, Frank U; Sendler, Matthias; Lerch, Markus M

    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

  13. The rat as animal model in breast cancer research: a histopathological study of radiation- and hormone-induced rat mammary tumors

    International Nuclear Information System (INIS)

    One of the goals of this monograph is to present data on the frequency of mammary neoplasms following irradiation and/or hormone administration in intact and castrated female rats of three strains allowed to live their natural life spans. These data are intended to give an overview of the effects of radiation and hormonal manipulation on the mammary gland based on histological examination of necropsied rats and using standard morphological criteria for mammary tumors. The second goal of this monograph is to provide detailed histological descriptions of the mammary tumors found in the various experimental groups as well as in several groups of untreated control rats. The aims are to examine whether possible strain-related and treatment-related differences in morphology or growth patterns exist, as well as to define the pathogensis of radiation-induced rat mammary tumors through the study of early lesions. An attempt will be made to describe tumor characteristics which may be of comparative value in identifying tumor types (and their induction methods) useful as models for specific human breast neoplasms. A rat mammary tumor classification system reflecting the morphological features useful for comparative purposes is also presented. (Auth.)

  14. ANIMAL MODELS: A REVIEW FROM THREE TESTS USED IN ANXIETY

    OpenAIRE

    Manuel Eduardo Góngora; Cristina Vargas-Irwin; Lady Andrea Polanco

    2011-01-01

    The aim of this paper is to present a review of commonly used animal models tostudy anxiety, looking to make a presentation of three instruments used in thelaboratory. It describes the importance of using animal models for understandinghuman behavior; there are two groups of animal models and the most representativetests for each of these.

  15. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    Full Text Available

    The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.

    Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.

    The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.

    This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.

    Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models

  16. Animal models of bronchopulmonary dysplasia. The preterm baboon models

    OpenAIRE

    Yoder, Bradley A.; Coalson, Jacqueline J.

    2014-01-01

    Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the...

  17. In vivo fluorescence enhanced optical tomography reconstruction of lung cancer of non immersed small animals

    Science.gov (United States)

    Hervé, L.; Koenig, A.; Da Silva, A.; Berger, M.; Boutet, J.; Dinten, J. M.; Peltié, P.; Rizo, P.

    2007-02-01

    Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.

  18. Mouse models for cancer research

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Lynette Moore; Ping Ji

    2011-01-01

    Mouse models of cancer enable researchers to leamn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Joumnal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue.

  19. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

    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

  20. 建立乳腺癌骨转移动物模型方法的比较研究%A comparative study of four methods for establishing animal models of human breast cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    张帆; 姜军; 齐晓伟; 唐鹏; 陈庆秋

    2010-01-01

    Objective To investigate four methods for establishing animal models of human breast cancer bone metastasis. Methods Thirty-two female nude mice aged 4-6 weeks were divided randomly into four groups (n=8 in each group). 5×105 MDA-MB-231 cells were injected into the body via the left second mammary fat pads (group A), the tail veins (group B), the left heart ventricles (group C) and the left tibia marrow cavities (group D), respectively. Tumor formations in situ were recorded in group A. Deaths after the injection were recorded. The surviving nude mice 49 days after the injection were subjected to pathological examination to determine bone metastasis. Results The rate of tumor formation in situ of group A was87.5 %(7/8). One mouse in group C died after the injection of MDA-MB-231 cells. The bone metastasis rate in groups A, B, C and D was zero (0/8), 12.5 % (1/8), 71.4 % (5/7) and 100 % (8/8), respectively. There was statistically significant difference in the bone metastasis rate between group A and group C, group A and group D, group B and group C; and group B and group D. Conclusion Injections of tumor cells via the breast fat pads and tail veins were not suitablemethods to establish animal models of human breast cancer bone metastasis. The bone metastasis model could be established efficiently by injecting tumor cells into the left heart ventricles or the bone marrow cavity of nude mice.%目的 对四种乳腺癌骨转移动物模型的构建方法进行比较研究.方法 32只4-6周龄雌性裸鼠随机分为A、B、C、D 4组,每组8只,每只裸鼠以5×105个MDA-MB-231细胞按分组分别注射入左第二乳房脂肪垫、尾静脉、左心室和左胫骨骨髓腔.观察A组裸鼠乳腺原位成瘤情况、全组注射致死情况和全组49 d后骨转移发生情况.结果 A组乳腺原位移植瘤形成率为87.5%(7/8).仅C组注射致死裸鼠1只.各组骨转移发生率分别为:0(0/8)、12.5%(1/8)、71.4%(5/7)、100%(8/8).A组和C组、A组和D组

  1. 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.

  2. RASopathies: unraveling mechanisms with animal models.

    Science.gov (United States)

    Jindal, Granton A; Goyal, Yogesh; Burdine, Rebecca D; Rauen, Katherine A; Shvartsman, Stanislav Y

    2015-08-01

    RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births) motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment. PMID:26203125

  3. Information Learned from Animal Models of Atrial Fibrillation

    OpenAIRE

    Finet, J. Emanuel; Rosenbaum, David S.; Donahue, J. Kevin

    2009-01-01

    Animal models of atrial fibrillation have taught us about mechanisms of this common disease. A variety of animal models exist, including models of lone atrial fibrillation and models of atrial fibrillation in the setting of heart failure, aging or pericardial inflammation. This chapter reviews these various models.

  4. Models for prevention and treatment of cancer: problems vs promises.

    Science.gov (United States)

    Aggarwal, Bharat B; Danda, Divya; Gupta, Shan; Gehlot, Prashasnika

    2009-11-01

    Current estimates from the American Cancer Society and from the International Union Against Cancer indicate that 12 million cases of cancer were diagnosed last year, with 7 million deaths worldwide; these numbers are expected to double by 2030 (27 million cases with 17 million deaths). Despite tremendous technological developments in all areas, and President Richard Nixon's initiative in the 1974 "War against Cancer", the US cancer incidence is the highest in the world and the cancer death rate has not significantly changed in the last 50 years (193.9 per 100,000 in 1950 vs 193.4 per 100,000 in 2002). Extensive research during the same time, however, has revealed that cancer is a preventable disease that requires major changes in life style; with one third of all cancers assigned to Tobacco, one third to diet, and remaining one third to the environment. Approximately 20 billion dollars are spent annually to find a cure for cancer. We propose that our inability to find a cure to cancer lies in the models used. Whether cell culture or animal studies, no model has yet been found that can reproduce the pathogenesis of the disease in the laboratory. Mono-targeted therapies, till know in most cases, have done a little to make a difference in cancer treatment. Similarly, molecular signatures/predictors of the diagnosis of the disease and response are also lacking. This review discusses the pros and cons of current cancer models based on cancer genetics, cell culture, animal models, cancer biomarkers/signature, cancer stem cells, cancer cell signaling, targeted therapies, therapeutic targets, clinical trials, cancer prevention, personalized medicine, and off-label uses to find a cure for cancer and demonstrates an urgent need for "out of the box" approaches. PMID:19481061

  5. Models for prevention and treatment of cancer: problems vs promises.

    Science.gov (United States)

    Aggarwal, Bharat B; Danda, Divya; Gupta, Shan; Gehlot, Prashasnika

    2009-11-01

    Current estimates from the American Cancer Society and from the International Union Against Cancer indicate that 12 million cases of cancer were diagnosed last year, with 7 million deaths worldwide; these numbers are expected to double by 2030 (27 million cases with 17 million deaths). Despite tremendous technological developments in all areas, and President Richard Nixon's initiative in the 1974 "War against Cancer", the US cancer incidence is the highest in the world and the cancer death rate has not significantly changed in the last 50 years (193.9 per 100,000 in 1950 vs 193.4 per 100,000 in 2002). Extensive research during the same time, however, has revealed that cancer is a preventable disease that requires major changes in life style; with one third of all cancers assigned to Tobacco, one third to diet, and remaining one third to the environment. Approximately 20 billion dollars are spent annually to find a cure for cancer. We propose that our inability to find a cure to cancer lies in the models used. Whether cell culture or animal studies, no model has yet been found that can reproduce the pathogenesis of the disease in the laboratory. Mono-targeted therapies, till know in most cases, have done a little to make a difference in cancer treatment. Similarly, molecular signatures/predictors of the diagnosis of the disease and response are also lacking. This review discusses the pros and cons of current cancer models based on cancer genetics, cell culture, animal models, cancer biomarkers/signature, cancer stem cells, cancer cell signaling, targeted therapies, therapeutic targets, clinical trials, cancer prevention, personalized medicine, and off-label uses to find a cure for cancer and demonstrates an urgent need for "out of the box" approaches.

  6. Animal Models of Ischemic Stroke. Part Two: Modeling Cerebral Ischemia

    OpenAIRE

    Bacigaluppi, Marco; Comi, Giancarlo; Dirk M Hermann

    2010-01-01

    Animal models of stroke provide an essential tool for the understanding of the complex cellular and molecular pathophysiology of stroke and for testing novel recanalyzing, neuroprotective, neuroregenerative or anti- inflammatory drugs in pre- clinical setting. Since the first description of the distal occlusion of the middle cerebral artery (MCA) in rats, different techniques and methods to induce focal and global ischemia of the brains have been developed and optimized. The different models,...

  7. Animal model of Mycoplasma fermentans respiratory infection

    Directory of Open Access Journals (Sweden)

    Yáñez Antonio

    2013-01-01

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

  8. Modeling dopamine system dysfunction in experimental animals

    International Nuclear Information System (INIS)

    Quite a substantial number of human disorders have been associated with a primary or a secondary impairment of one or several of the dopaminergic pathways. Among disorders associated with a primary impairment of dopaminergic transmission are Parkinson's disease, striatonigral degeneration, progressive supranuclear palsy, and possibly schizophrenia. Diseases of secondary dopamine dysfunction are chiefly represented by Huntington's disease in which dopaminergic transmission is being interrupted by progressive loss of the striatal neurons bearing the postsynaptic D1- and D2-dopamine receptors. Central dopaminergic systems have anatomical as well as organizational properties that render them unique by comparison to other neurotransmission systems, making them able to play a pivotal role in the modulation of various important brain functions such as locomotor activity, attention, and some cognitive abilities. These properties of dopamine neurons have obviously several implications in the clinical expression of human disorders involving dopamine neuron dysfunction. In addition, they can greatly influence the clinical/behavioral consequences of experimental lesions in animal models of dopamine dysfunctions

  9. The maternal deprivation animal model revisited.

    Science.gov (United States)

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

    2015-04-01

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

  10. Systematic Review of Traumatic Brain Injury Animal Models.

    Science.gov (United States)

    Phipps, Helen W

    2016-01-01

    The goals of this chapter are to provide an introduction into the variety of animal models available for studying traumatic brain injury (TBI) and to provide a concise systematic review of the general materials and methods involved in each model. Materials and methods were obtained from a literature search of relevant peer-reviewed articles. Strengths and weaknesses of each animal choice were presented to include relative cost, anatomical and physiological features, and mechanism of injury desired. Further, a variety of homologous, isomorphic/induced, and predictive animal models were defined, described, and compared with respect to their relative ease of use, characteristics, range, adjustability (e.g., amplitude, duration, mass/size, velocity, and pressure), and rough order of magnitude cost. Just as the primary mechanism of action of TBI is limitless, so are the animal models available to study TBI. With such a wide variety of available animals, types of injury models, along with the research needs, there exists no single "gold standard" model of TBI rendering cross-comparison of data extremely difficult. Therefore, this chapter reflects a representative sampling of the TBI animal models available and is not an exhaustive comparison of every possible model and associated parameters. Throughout this chapter, special considerations for animal choice and TBI animal model classification are discussed. Criteria central to choosing appropriate animal models of TBI include ethics, funding, complexity (ease of use, safety, and controlled access requirements), type of model, model characteristics, and range of control (scope). PMID:27604713

  11. Laboratory Animal Models for Brucellosis Research

    OpenAIRE

    Silva, Teane M. A.; Erica A Costa; Tatiane A. Paixão; Renée M. Tsolis; Santos, Renato L

    2011-01-01

    Brucellosis is a chronic infectious disease caused by Brucella spp., a Gram-negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated...

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

    OpenAIRE

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

    2015-01-01

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmenta...

  13. Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Masaaki Kodama; Kazunari Murakami; Ryugo Sato; Tadayoshi Okimoto; Akira Nishizono; Toshio Fujioka

    2005-01-01

    Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (Hpylori), several animal models with Hpylori infection have been developed to confirm the association between Hpylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53mutation after long-term infection of Hpylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methylN-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine.The histopathological changes of these animal models after Hpylori inoculation are closely similar to those in human beings with Hpylori infection. Eradication therapy attenuated the development of gastric cancer in Hpyloriinfected Mongolian gerbil. Although several features of animal models differ from those seen in human beings,these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of Hpylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

  14. Dietary Zinc and Prostate Cancer in the TRAMP Mouse Model

    OpenAIRE

    Prasad, Ananda S; Mukhtar, Hasan; Beck, Frances W.J.; Adhami, Vaqar M.; Siddiqui, Imtiaz A.; Din, Maria; Hafeez, Bilal B.; KUCUK, Omer

    2010-01-01

    Circumstantial evidence indicates that zinc may have an important role in the prostate. Total zinc levels in the prostate are 10 times higher than in other soft tissues. Zinc concentrations in prostate epithethial cancer cells are decreased significantly. Zinc supplementation for prevention and treatment of prostate cancer in humans has yielded controversial results. No studies have been reported in animal models to show the effect of zinc supplementation on prevention of prostate cancer, thu...

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

    International Nuclear Information System (INIS)

    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

  16. Animal models of traumatic brain injury : a critical evaluation

    OpenAIRE

    O'Connor, William; Smyth, Aoife; Gilchrist, M. D.

    2011-01-01

    Animal models are necessary to elucidate changes occurring after brain injury and to establish new therapeutic strategies towards a stage where drug efficacy in brain injured patients (against all classes of symptoms) can be predicted. In this review, six established animal models of head trauma, namely fluid percussion, rigid indentation, inertial acceleration, impact acceleration, weight-drop and dynamic cortical deformation are evaluated. While no single animal model is entirely successful...

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

    OpenAIRE

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

    2016-01-01

    Tourette syndrome (TS) is a childhood onset disorder characterized by motor and vocal tics and associated with multiple comorbid symptoms. Over the last decade, the accumulation of findings from TS patients and the emergence of new technologies have led to the development of novel animal models with high construct validity. In addition, animal models which were previously associated with other disorders were recently attributed to TS. The proliferation of TS animal models has accelerated TS r...

  18. Animal models of attention-deficit hyperactivity disorder

    OpenAIRE

    Sagvolden Terje; Russell Vivienne A; Johansen Espen

    2005-01-01

    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 funct...

  19. Three-dimensional in vitro cancer models: a short review

    International Nuclear Information System (INIS)

    The re-creation of the tumor microenvironment including tumor–stromal interactions, cell–cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell–cell and cell–matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies. (topical review)

  20. Aspects of animal models for major neuropsychiatric disorders

    OpenAIRE

    Lefter Radu; Cojocaru Dumitru; Ciobica Alin; Paulet Manuel Ioan; Serban Lacramioara Ionela; Anton Emil

    2014-01-01

    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 t...

  1. 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

  2. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  12. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  13. Towards an animal model for retinoblastoma

    NARCIS (Netherlands)

    Bernards, R.A.; O'Brien, J.M.; Marcus, D.M.; Albert, D.M.; Jacks, T.; Weinberg, R.A.

    1989-01-01

    Within the past decade a large repertoire of cellular oncogenes has been implicated in the genesis of many types of cancers. These oncogenes all function to promote the neoplastic growth of cells in which they act. Indeed, they all appear to derive from normal cell genes, proto-oncogenes, which act

  14. Preclinical fluorescent mouse models of pancreatic cancer

    Science.gov (United States)

    Bouvet, Michael; Hoffman, Robert M.

    2007-02-01

    Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent protein (RFP). Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. We have shown a high correlation between florescent optical imaging and magnetic resonance imaging in these models. Alternatively, transplantation of RFP-expressing tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. An Integrated Approach to Flexible Modelling and Animated Simulation

    Institute of Scientific and Technical Information of China (English)

    Li Shuliang; Wu Zhenye

    1994-01-01

    Based on the software support of SIMAN/CINEMA, this paper presents an integrated approach to flexible modelling and simulation with animation. The methodology provides a structured way of integrating mathematical and logical model, statistical experinentation, and statistical analysis with computer animation. Within this methodology, an animated simulation study is separated into six different activities: simulation objectives identification , system model development, simulation experiment specification, animation layout construction, real-time simulation and animation run, and output data analysis. These six activities are objectives driven, relatively independent, and integrate through software organization and simulation files. The key ideas behind this methodology are objectives orientation, modelling flexibility,simulation and animation integration, and application tailorability. Though the methodology is closely related to SIMAN/CINEMA, it can be extended to other software environments.

  17. Animation of 3D Model of Human Head

    Directory of Open Access Journals (Sweden)

    V. Michalcin

    2007-04-01

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

  18. Contribution of customised dosimetry for small animal to the treatments of cancers by metabolic radiotherapy

    International Nuclear Information System (INIS)

    This research thesis first reports a bibliographical study which addressed the use of ionizing radiations in cancer therapy (evolution from ionizing radiation to metabolic radiotherapy, biological and physical parameters, and absorbed dose in metabolic radiotherapy) and the role imagery has in customised dosimetry (absorbed dose calculation methods, determination of cumulative activity, dosimetric models for S factor calculation). Then, the author presents a software which has been specifically developed for the creation of dosimetric models, and reports its validation. He reports the comparison between different dosimetric models in the case of mice. He highlights two applications of the developed tool: radio-immunotherapy and metabolic radiotherapy. He finally proposes a general discussion on the impact of small animal dosimetry on metabolic radiotherapy

  19. Rabbit as an animal model for experimental research

    OpenAIRE

    Manjeet Mapara; Betsy Sara Thomas; Bhat, K M

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. T...

  20. Lessons Learned from Animal Models of Inherited Bleeding Disorders

    OpenAIRE

    Nichols, Timothy C.

    2014-01-01

    Advances in treatment of hemophilia and von Willebrand disease (VWD) depend heavily on the availability of well-characterized animal models. These animals faithfully recapitulate the severe bleeding phenotype that occurs in humans with these inherited bleeding disorders. Research in these animal models represents important early and intermediate steps of translational research aimed at addressing current limitations in treatment such as the development of inhibitory antibodies to coagulation ...

  1. Animal models for photodynamic therapy (PDT)

    OpenAIRE

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

    2015-01-01

    Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for...

  2. Animal models of human response to dioxins.

    OpenAIRE

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

    1998-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine functio...

  3. Overview of Vertebrate Animal Models of Fungal Infection

    OpenAIRE

    Hohl, Tobias M

    2014-01-01

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

  4. Animal Models of Cardiac Disease and Stem Cell Therapy

    OpenAIRE

    Ou, Lailiang; Li, Wenzhong; Liu, Yi; Zhang, Yue(Walter Burke Institute for Theoretical Physics, California Institute of Technology, Pasadena, CA, 91125, U.S.A.); Jie, Shen; Kong, Deling; Steinhoff, Gustav; Ma, Nan

    2010-01-01

    Animal models that mimic cardiovascular diseases are indispensable tools for understanding the mechanisms underlying the diseases at the cellular and molecular level. This review focuses on various methods in preclinical research to create small animal models of cardiac diseases, such as myocardial infarction, dilated cardiomyopathy, heart failure, myocarditis and cardiac hypertrophy, and the related stem cell treatment for these diseases.

  5. Animal Models for HIV Cure Research

    OpenAIRE

    Benjamin B Policicchio; Pandrea, Ivona; Apetrei, Cristian

    2016-01-01

    The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal ...

  6. 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...

  7. Application of Animal Modeling to Biodefense Research

    Institute of Scientific and Technical Information of China (English)

    Mark; A.; Suckow; ACLAM

    2005-01-01

    The use of biological agents to attack enemies has substantial historical precedent,and includes documented attempts tocontaminate the wells andreservoirs of enemies withcadavers and animal carcasses;and attemptstoinfect Native Ameri-cans with smallpox via contaminated blankets offered as gifts.Awareness and concern over biological weapons has in-creased greatly as the technological sophistication required to produce related agents has become more global.That theuse of biological agents as a means of aggres...

  8. Animal learning models as robot controllers

    OpenAIRE

    Hallam, Bridget

    2000-01-01

    Robots can do a range of wonderful things, but they can also appear really stupid. I would like my autonomous, sensor-rich, robot to be able to: complete its task whenever possible, despite distractions and disabilities; learn the best, most reliable cues for success of the various task components; have sensible default actions whenever the situation is unknown; cope with an unpredictably changing environment; and pay attention whenever I want to contact it. Dreamland? At the moment. Yet anim...

  9. 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.

  10. Antiangiogenic cancer drug using the zebrafish model.

    Science.gov (United States)

    Santoro, Massimo M

    2014-09-01

    The process of de novo vessel formation, called angiogenesis, is essential for tumor progression and spreading. Targeting of molecular pathways involved in such tumor angiogenetic processes by using specific drugs or inhibitors is important for developing new anticancer therapies. Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. To pursue these molecular and pharmacological goals, researchers need to use animal models that facilitate the elucidation of tumor angiogenesis mechanisms and the testing of antiangiogenic therapies. The past few years have seen the zebrafish system emerge as a valid model organism to study developmental angiogenesis and, more recently, as an alternative vertebrate model for cancer research. In this review, we will discuss why the zebrafish model system has the advantage of being a vertebrate model equipped with easy and powerful transgenesis as well as imaging tools to investigate not only physiological angiogenesis but also tumor angiogenesis. We will also highlight the potential of zebrafish for identifying antitumor angiogenesis drugs to block tumor development and progression. We foresee the zebrafish model as an important system that can possibly complement well-established mouse models in cancer research to generate novel insights into the molecular mechanism of the tumor angiogenesis. PMID:24903092

  11. The significant human-animal bond: Pets with cancer

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    Veterinarians have responsibilities to both the animal and its owner. In the past several years there has been an increased awareness and concern about human-animal bonds. As a result, we have begun to appreciate the nature, strength, and significance of bonds that develop between humans and companion animals. It is typical for a pet to be perceived as and treated as a member of the family and as a result, animals provide special and beneficial relationships for many years. It is partly because of this role of the pet in promoting human health and happiness that we as veterinarians have an obligation to assist both owner and animal. The mark of the good practitioner concerns not only the ability to diagnose and treat accurately, but also the ability to show understanding and compassionate judgement.

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

    Science.gov (United States)

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

    2015-07-15

    The translational value of animal models is an issue of ongoing discussion. We argue that 'Refinement' of animal experiments is needed and this can be achieved by exploiting an ethological approach when setting up and conducting experiments. Ethology aims to assess the functional meaning of behavioral changes, due to experimental manipulation or treatment, in animal models. Although the use of ethological concepts is particularly important for studies involving the measurement of animal behavior (as is the case for most studies on neuro-psychiatric conditions), it will also substantially benefit other disciplines, such as those investigating the immune system or inflammatory response. Using an ethological approach also involves using more optimal testing conditions are employed that have a biological relevance to the animal. Moreover, using a more biological relevant analysis of the data will help to clarify the functional meaning of the modeled readout (e.g. whether it is psychopathological or adaptive in nature). We advocate for instance that more behavioral studies should use animals in group-housed conditions, including the recording of their ultrasonic vocalizations, because (1) social behavior is an essential feature of animal models for human 'social' psychopathologies, such as autism and schizophrenia, and (2) social conditions are indispensable conditions for appropriate behavioral studies in social species, such as the rat. Only when taking these elements into account, the validity of animal experiments and, thus, the translation value of animal models can be enhanced. PMID:25823814

  13. Infectious diseases among animals : combining models with data

    OpenAIRE

    de Koeijer, A.A.

    2003-01-01

    To eradicate or control the spread of infectious diseases, knowledge on the spread of the infection between (groups of) animals is necessary. Models can include such information and can subsequently be used to observe the efficacy of various control measures in fighting the infection. However, the availability of information and data to build and quantify these models is essential for applying such models in real life. In this thesis, models on the spread of infectious diseases in animals are...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Greek, Ray; Menache, Andre

    2013-01-01

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

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

    Science.gov (United States)

    Ma, Xiaohan; Deng, Zhigang

    2012-11-01

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

  17. Animals

    International Nuclear Information System (INIS)

    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)

  18. Penile autotransplantation in rats: An animal model

    Directory of Open Access Journals (Sweden)

    Raouf M Seyam

    2013-01-01

    Conclusions: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

  19. High Resolution X-ray Computed Tomography: An Emerging Tool for Small Animal Cancer Research

    OpenAIRE

    Paulus, Michael J.; Gleason, Shaun S; Kennel, Stephen J.; Hunsicker, Patricia R.; Johnson, Dabney K.

    2000-01-01

    Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for cancer research. These new imaging systems permit researchers to noninvasively screen animals for mutations or pathologies and to monitor disease progression and response to therapy. One imaging modality, X-ray microcomputed tomography (microCT) shows promise as a cost-effective means for detecting and characterizing soft-tissue structures, skeletal abnormalities, and tumors in live animals...

  20. High Resolution X-ray Computed Tomography: An Emerging Tool for Small Animal Cancer Research1

    OpenAIRE

    Paulus, Michael J.; Gleason, Shaun S; Kennel, Stephen J.; Hunsicker, Patricia R.; Johnson, Dabney K.

    2000-01-01

    Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for cancer research. These new imaging systems permit researchers to noninvasively screen animals for mutations or pathologies and to monitor disease progression and response to therapy. One imaging modality, X-ray microcomputed tomography (microCT) shows promise as a cost-effective means for detecting and characterizing soft-tissue structures, skeletal abnormalities, and tumors in live animals...

  1. The motivations and methodology for high-throughput PET imaging of small animals in cancer research

    OpenAIRE

    Aide, Nicolas; Visser, Eric P.; Lheureux, Stéphanie; Heutte, Natacha; Szanda, Istvan; Hicks, Rodney J.

    2012-01-01

    Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the num...

  2. Animal Models of Substance Abuse and Addiction: Implications for Science, Animal Welfare, and Society

    OpenAIRE

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

    2010-01-01

    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...

  3. Animal models for mucopolysaccharidosis disorders and their clinical relevance

    OpenAIRE

    Haskins, Mark E.

    2007-01-01

    Progress in understanding how a particular genotype produces the phenotype of an inborn error of metabolism, such as a mucopolysaccharidosis, in human patients has been facilitated by the study of animals with mutations in the orthologous genes. These are not just animal models, but true orthologues of the human genetic disease, with defects involving the same evolutionarily conserved genes and the same molecular, biochemical, and anatomic lesions as in human patients. These animals are often...

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

    OpenAIRE

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

    2008-01-01

    Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome th...

  5. Sex differences in animal models of psychiatric disorders

    OpenAIRE

    Kokras, N.; Dalla, C.

    2014-01-01

    Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnos...

  6. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  7. 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.

  8. 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. PMID:25991698

  9. Using animal models to develop new treatments for tuberculosis.

    Science.gov (United States)

    Nuermberger, Eric

    2008-10-01

    Animal models have an important role in the preclinical evaluation of new antituberculosis drug candidates. Although it does not recapitulate the clinicopathological manifestations of tuberculosis in humans, the mouse remains the best characterized and most economical animal model for experimental chemotherapy. Provided care is taken to optimize the experimental conditions, the mouse has produced reliable data on the bactericidal and sterilizing activity of existing antituberculosis drugs and informed numerous clinical trials. Still, other animal models, especially the guinea pig, may have utility as confirmatory, or even alternative, models under certain circumstances. This chapter reviews some of the important considerations when selecting an animal model and presents a model for the sequential evaluation of a new compound with promising antituberculosis activity.

  10. Non-linearity between dose and cancer risk for internally deposited alpha emitters in animals

    International Nuclear Information System (INIS)

    The risk of cancer in experimental animals exposed to low doses and dose rates of internally deposited alpha emitting radionuclides was analyzed in 27 animal experiments comprising 78 groups exposed to specific dose levels (dose groups). In these experiments, 3041 animals were exposed to eight different alpha emitters, by injection or by inhalation. Radiation doses ranged from about 60 mGy to more than 7 Gy. There were 1655 control animals. The target organs were the lung and the skeleton. The cancer incidence in exposed groups was compared to that predicted by the Linear No-Threshold Hypothesis (LNTH). In the 3041 exposed animals, 49 cancers were observed, against 83 predicted by the LNTHT. The LNTH appears to be a reliable risk predictor in 11 of the 78 dose groups, but it overestimates the risk in the 67 other dose groups (71 predicted cases, 8 cases observed). No cancer was observed in 53 dose groups, when 23 were predicted by the LNTH. In these 53 dose groups, the probability of not observing a single case of cancer was extremely small. These observations led to the conclusion that, at least in the case of alpha emitters with long physical and biological half-lives, the LNTH is not a good predictor of the risk of cancer. (author)

  11. Reverse translational strategies for developing animal models of bipolar disorder

    OpenAIRE

    Malkesman, Oz; Austin, Daniel R.; Chen, Guang; Manji, Husseini K

    2009-01-01

    Bipolar disorder (BD) affects a significant portion of the population of the world, yet there has been limited success in developing novel treatments for the disorder. One of the major reasons for this dearth is the absence of suitable animal models for BD. Traditionally, animal models of human phenomena have been evaluated based on similarity to the human syndrome, response to appropriately corresponding medications, and the degree to which a model supports a common mechanistic theory betwee...

  12. Animal models for the study of arterial hypertension

    Indian Academy of Sciences (India)

    Waleska C Dornas; Marcelo E Silva

    2011-09-01

    Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

  13. Peripheral Biomarkers in Animal Models of Major Depressive Disorder

    OpenAIRE

    Lucia Carboni

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with M...

  14. 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

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

    OpenAIRE

    Dong, Wen; Wang, Rong

    2015-01-01

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

  16. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  17. An updated overview of animal models in neuropsychiatry.

    Science.gov (United States)

    Razafsha, M; Behforuzi, H; Harati, H; Wafai, R Al; Khaku, A; Mondello, S; Gold, M S; Kobeissy, F H

    2013-06-14

    Animal models are vital tools to study the genetic, molecular, cellular, and environmental parameters involved in several neuropsychiatric disorders. Over the years, these models have expanded our understanding of the pathogenesis of many neuropsychiatric disorders and neurodegenerative diseases. Although animal models have been widely used in psychiatry, and despite several years of extensive research with these models, their validity is still being investigated and presents a challenge to both investigators and clinicians as well. In this concise review, we will describe the most common animal models utilized in neuropsychiatry, including animal models of depression, anxiety, and psychosis. In addition, we will also discuss the validity and reliability of these models and current challenges in this domain. Furthermore, this work will discuss the role of gene-environment interaction as an additional contributing factor that modulates neuropsychological outcome and its implication on animal models. This overview will give a succinct summary of animal models in psychiatry which will be useful both to the seasoned researcher, as well as novices in the field. PMID:23473749

  18. Developing better and more valid animal models of brain disorders.

    Science.gov (United States)

    Stewart, Adam Michael; Kalueff, Allan V

    2015-01-01

    Valid sensitive animal models are crucial for understanding the pathobiology of complex human disorders, such as anxiety, autism, depression and schizophrenia, which all have the 'spectrum' nature. Discussing new important strategic directions of research in this field, here we focus i) on cross-species validation of animal models, ii) ensuring their population (external) validity, and iii) the need to target the interplay between multiple disordered domains. We note that optimal animal models of brain disorders should target evolutionary conserved 'core' traits/domains and specifically mimic the clinically relevant inter-relationships between these domains. PMID:24384129

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

    Directory of Open Access Journals (Sweden)

    W Reizner

    2014-03-01

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

  20. Progress in Adaptive Immunotherapy for Cancer in Companion Animals: Success on the Path to a Cure

    Directory of Open Access Journals (Sweden)

    Katie L. Anderson

    2015-10-01

    Full Text Available Harnessing the ability of the immune system to eradicate cancer has been a long-held goal of oncology. Work from the last two decades has finally brought immunotherapy into the forefront for cancer treatment, with demonstrable clinical success for aggressive tumors where other therapies had failed. In this review, we will discuss a range of therapies that are in different stages of clinical or preclinical development for companion animals with cancer, and which share the common objective of eliciting adaptive, anti-tumor immune responses. Even though challenges remain, manipulating the immune system holds significant promise to create durable responses and improve outcomes in companion animals with cancer. Furthermore, what we learn from this process will inform and accelerate development of comparable therapies for human cancer patients.

  1. 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.

  2. Animal models in epigenetic research: institutional animal care and use committee considerations across the lifespan.

    Science.gov (United States)

    Harris, Craig

    2012-01-01

    The rapid expansion and evolution of epigenetics as a core scientific discipline have raised new questions about how endogenous and environmental factors can inform the mechanisms through which biological form and function are regulated. Existing and proposed animal models used for epigenetic research have targeted a myriad of health and disease endpoints that may be acute, chronic, and transgenerational in nature. Initiating events and outcomes may extend across the entire lifespan to elicit unanticipated phenotypes that are of particular concern to institutional animal care and use committees (IACUCs). The dynamics and plasticity of epigenetic mechanisms produce effects and consequences that are manifest differentially within discreet spatial and temporal contexts, including prenatal development, stem cells, assisted reproductive technologies, production of sexual dimorphisms, senescence, and others. Many dietary and nutritional interventions have also been shown to have a significant impact on biological functions and disease susceptibilities through altered epigenetic programming. The environmental, chemical, toxic, therapeutic, and psychosocial stressors used in animal studies to elicit epigenetic changes can become extreme and should raise IACUC concerns for the well-being and proper care of all research animals involved. Epigenetics research is rapidly becoming an integral part of the search for mechanisms in every major area of biomedical and behavioral research and will foster the continued development of new animal models. From the IACUC perspective, care must be taken to acknowledge the particular needs and concerns created by superimposition of epigenetic mechanisms over diverse fields of investigation to ensure the proper care and use of animals without impeding scientific progress.

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

    Science.gov (United States)

    Mabunga, Darine Froy N; Gonzales, Edson Luck T; Kim, Ji-Woon; Kim, Ki Chan; Shin, Chan Young

    2015-12-01

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

  4. GHRH treatment: studies in an animal model.

    Science.gov (United States)

    Shakutsui, S; Abe, H; Chihara, K

    1989-01-01

    This study examined the effects of chronic deletion of circulating growth hormone-releasing (GHRH) and/or somatostatin (SRIF) on normal growing male rats, as well as the effects of exogenous GHRH (1-29)NH2 and/or SMS 201-995 administration on the growth of rats with hypothalamic ablation. Passive immunization with anti-rat GHRH goat gamma-globulin (GHRH-Ab) for 3 weeks caused a marked decrease in the levels of pituitary GH mRNA and severe growth failure. Treatment with anti-SRIF goat gamma-globulin (SRIF-Ab) for 3 weeks produced a more modest decrease in GH mRNA levels in the pituitary and a slight but significant inhibition of normal somatic growth. Hypothalamic ablation produced a marked decrease in the level of mRNA in the pituitary. Chronic continuous administration of GHRH (1-29)NH2 stimulated pituitary GH synthesis, elevated serum levels of insulin-like growth factor I and increased body weight gain in rats with hypothalamic ablation treated with replacement doses of cortisone, testosterone and L-thyroxine. Combined treatment with GHRH (1-29)NH2 and SMS 201-995 appeared to promote the effect of GHRH on pituitary GH release and somatic growth in these animals. The results suggest that continuous administration of GHRH will be useful in the treatment of children with growth retardation resulting from hypothalamic disorders. In children with combined GHRH and somatostatin deficiencies, the addition of somatostatin to a GHRH treatment regimen may produce better results. PMID:2568726

  5. Animal models for screening anxiolytic-like drugs: a perspective.

    Science.gov (United States)

    Bourin, Michel

    2015-09-01

    Contemporary biological psychiatry uses experimental animal models to increase our understanding of affective disorder pathogenesis. Modern anxiolytic drug discovery mainly targets specific pathways and molecular determinants within a single phenotypic domain. However, greater understanding of the mechanisms of action is possible through animal models. Primarily developed with rats, animal models in anxiety have been adapted with mixed success for mice, easy-to-use mammals with better genetic possibilities than rats. In this review, we focus on the three most common animal models of anxiety in mice used in the screening of anxiolytics. Both conditioned and unconditioned models are described, in order to represent all types of animal models of anxiety. Behavioral studies require careful attention to variable parameters linked to environment, handling, or paradigms; this is also discussed. Finally, we focus on the consequences of re-exposure to the apparatus. Test-retest procedures can provide new answers, but should be intensively studied in order to revalidate the entire paradigm as an animal model of anxiety.

  6. 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.

  7. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    , substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation...... 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...

  8. 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.

  9. Effect of Xanthone Derivatives on Animal Models of Depression

    Directory of Open Access Journals (Sweden)

    Xu Zhao, MD

    2014-12-01

    Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.

  10. Leading compounds for the validation of animal models of psychopathology.

    Science.gov (United States)

    Micale, Vincenzo; Kucerova, Jana; Sulcova, Alexandra

    2013-10-01

    Modelling of complex psychiatric disorders, e.g., depression and schizophrenia, in animals is a major challenge, since they are characterized by certain disturbances in functions that are absolutely unique to humans. Furthermore, we still have not identified the genetic and neurobiological mechanisms, nor do we know precisely the circuits in the brain that function abnormally in mood and psychotic disorders. Consequently, the pharmacological treatments used are mostly variations on a theme that was started more than 50 years ago. Thus, progress in novel drug development with improved therapeutic efficacy would benefit greatly from improved animal models. Here, we review the available animal models of depression and schizophrenia and focus on the way that they respond to various types of potential candidate molecules, such as novel antidepressant or antipsychotic drugs, as an index of predictive validity. We conclude that the generation of convincing and useful animal models of mental illnesses could be a bridge to success in drug discovery. PMID:23942897

  11. Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

    Science.gov (United States)

    Burrai, G P; Tanca, A; De Miglio, M R; Abbondio, M; Pisanu, S; Polinas, M; Pirino, S; Mohammed, S I; Uzzau, S; Addis, M F; Antuofermo, E

    2015-11-01

    Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22% of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer. PMID:26088453

  12. Animal models of post-traumatic stress disorder: face validity

    OpenAIRE

    Denis Pare

    2013-01-01

    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...

  13. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    OpenAIRE

    Md. Shahidul Islam

    2013-01-01

    Diabetic or peripheral diabetic neuropathy (PDN) is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat...

  14. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    OpenAIRE

    Xin-Fang Leong; Chun-Yi Ng; Kamsiah Jaarin

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Co...

  15. Analysis of animal accelerometer data using hidden Markov models

    OpenAIRE

    Leos-Barajas, Vianey; Photopoulou, Theoni; Langrock, Roland; Patterson, Toby A; Watanabe, Yuuki; Murgatroyd, Megan; Papastamatiou, Yannis P.

    2016-01-01

    Use of accelerometers is now widespread within animal biotelemetry as they provide a means of measuring an animal's activity in a meaningful and quantitative way where direct observation is not possible. In sequential acceleration data there is a natural dependence between observations of movement or behaviour, a fact that has been largely ignored in most analyses. Analyses of acceleration data where serial dependence has been explicitly modelled have largely relied on hidden Markov models (H...

  16. Animal models of drug addiction: advantages and limitations

    OpenAIRE

    Quertemont, Etienne

    2006-01-01

    Various animal models have been developed to investigate the neurobiological and behavioral mechanisms of drug addiction. The most popular of these animal models include the locomotor sensitization paradigm, the place conditioning procedure and the self-administration technique. With these techniques, it is possible to mimic in rodents the major aspects of human drug addiction. The self-administration procedure is the most widely used and show an excellent natural and predictive validity. In ...

  17. What Constitutes a Relevant Animal Model of the Ketogenic Diet?

    OpenAIRE

    Gregory L Holmes

    2008-01-01

    Animal models of human disease have been enormously important in improving our understanding of the pathophysiological basis and the development of novel therapies. In epilepsy, modeling using both in vivo and in vitro preparations has provided insight into fundamental neuronal mechanisms. Indeed, much of our understanding of seizure mechanisms comes from animal studies. The conceptual advances in understanding basic mechanisms of epilepsies have been largely validated in humans, attesting to...

  18. Principles for developing animal models of military PTSD

    OpenAIRE

    Nikolaos P. Daskalakis; Yehuda, Rachel

    2014-01-01

    The extent to which animal studies can be relevant to military posttraumatic stress disorder (PTSD) continues to be a matter of discussion. Some features of the clinical syndrome are more easily modeled than others. In the animal literature, a great deal of attention is focused on modeling the characteristics of military exposures and their impact on measurable behaviors and biological parameters. There are many issues to consider regarding the ecological validity of predator, social defeat o...

  19. Promise and Pitfalls of Animal Models of Schizophrenia

    OpenAIRE

    Feifel, David; Shilling, Paul D.

    2010-01-01

    Animal models are indispensible tools for advancing understanding of the cause of any given disease and developing new treatments. Developing animal models for schizophrenia presents formidable challenges owing to the distinctively human nature of the symptoms that define it and the thus-far-obscured underlying biological mechanisms. Nevertheless, progress has been and continues to be made in this important field of endeavor. This article discusses the challenges facing investigators who seek...

  20. The rat as an animal model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind...... that of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat...... as an animal model of Alzheimer's disease....

  1. Animal models for information processing during sleep.

    Science.gov (United States)

    Coenen, A M L; Drinkenburg, W H I M

    2002-12-01

    Information provided by external stimuli does reach the brain during sleep, although the amount of information is reduced during sleep compared to wakefulness. The process controlling this reduction is called 'sensory' gating and evidence exists that the underlying neurophysiological processes take place in the thalamus. Furthermore, it is clear that stimuli given during sleep can alter the functional state of the brain. Two factors have been shown to play a crucial role in causing changes in the sleeping brain: the intensity and the relevance of the stimulus. Intensive stimuli arouse the brain, as well as stimuli having a high informational impact on the sleeping person. The arousal threshold for important stimuli is quite low compared to neutral stimuli. A central question in sleep research is whether associative learning, or in other words the formation of new associations between stimuli, can take place in a sleeping brain. It has been shown that simple forms of learning are still possible during sleep. In sleeping rats, it is proven that habituation, an active, simple form of learning not to respond to irrelevant stimuli, can occur. Moreover, there is evidence for the view that more complex associations can be modulated and newly formed during sleep. This is shown by two experimental approaches: an extinction paradigm and a latent inhibition (pre-exposure) paradigm. The presentation of non-reinforced stimuli during sleep causes slower extinction compared to the same presentation of these stimuli during wakefulness. Consistently, the suppressive capacity of a stimulus in the latent inhibition paradigm is less when previously pre-exposed during sleep, as compared to pre-exposure during wakefulness. Thus, while associative learning is not completely blocked during sleep, aspects of association formation are clearly altered. However, animal studies also clearly indicate that complex forms of learning are not possible during sleep. It is hypothesised that this

  2. 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;

  3. Small animal model for HIV-1 Disease

    Institute of Scientific and Technical Information of China (English)

    Yoshio; Koyanagi

    2005-01-01

    Development of a viral infection model of the humanimmune systemusingsmall animalsis animportant goal in biomedi-cal research,especiallyinstudiesof HIV-1infection.Thisis particularlyimportant since susceptibilityto HIV-1islimit-edto humans.The C.B-17-scid/scid-mouselacks mature Tand Bcells dueto a defective rearrangement of the Tcell re-ceptor andimmunoglobulin genes.Twotypes of humanlymphoid chimeras have been establishedin scid-mice.The firstsuccess withthe human mouse chimera was achieved.Human fetal liv...

  4. 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...

  5. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Directory of Open Access Journals (Sweden)

    Gillian M. Lavelle

    2016-01-01

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.

  6. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Science.gov (United States)

    McElvaney, Noel G.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF. PMID:27340661

  7. Development of animal models for hepatobiliary nuclear imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Hee; Park, Yun Hee; Ryu, Yeon Mi; Shin, Eun Kyung; Kim, Meyoung Kon [Korea University Medical College, Seoul (Korea, Republic of)

    2002-07-01

    Animal models for hepatobiliary disorders were classified into 2 different types: parenchymal hepatotoxicity and biliary-tract cholestasis. The purpose of this study was to develop animal models for hepatobiliary scintigraphy in evaluating a novel agents, such as {sup 99m}Tc-mercaptoacetyl triglycine(MAG3)-biocytin. Animal models were prepared by use of female Balb/c mice. Those were treated with 0.1, 0.5, and 2.5 ml/kg of carbon tetrachloride (CCl4) intraperitoneally for hepatotoxicity and with 30, 150, and 750 mg/kg of {alpha}-naphthylisothiocyanate (ANIT) to induce cholestasis. Dose of optimum was 0.5 ml/kg and 150 mg/kg for each model but lower (0.1 ml/kg and 30 mg/kg) and higher (2.5ml/kg and 750 mg/kg)were not be compatible for hepatobiliary models. Using these hepatobiliary models, {sup 99m}Tc-MAG3-biocytin scintigraphy was successfully carried out by using 4 parameters, e.g., peak liver/heat ratio (Rmax), peak ratio time (Tmax), half clearance time (HCT), and hepatic extraction fraction (HEF) for hepatotoxicity and cholestasis. Additionally, biochemical and histological analysis also resulted in confirming these animal models. Thus, we concluded that these animal models were highly likely to be efficient in evaluating hepatobiliary scintigraphic agent such as {sup 99m}Tc-MAG3-biocytin.

  8. Animal models of Tourette syndrome – from proliferation to standardization

    Directory of Open Access Journals (Sweden)

    Dorin eYael

    2016-03-01

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

  9. Animal models for studying dengue pathogenesis and therapy.

    Science.gov (United States)

    Chan, Kitti Wing Ki; Watanabe, Satoru; Kavishna, Ranmali; Alonso, Sylvie; Vasudevan, Subhash G

    2015-11-01

    Development of a suitable animal model for dengue virus disease is critical for understanding pathogenesis and for preclinical testing of antiviral drugs and vaccines. Many laboratory animal models of dengue virus infection have been investigated, but the challenges of recapitulating the complete disease still remain. In this review, we provide a comprehensive coverage of existing models, from man to mouse, with a specific focus on recent advances in mouse models for addressing the mechanistic aspects of severe dengue in humans. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery.

  10. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis (NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  11. Modeling Leadership Hierarchy in Multilevel Animal Societies

    CERN Document Server

    Ozogány, Katalin

    2014-01-01

    A typical feature of many natural and social networks is the presence of communities giving rise to multiple levels of organization. We investigate the decision-making process of a group combining self organization and social dynamics, and reproduce the simultaneous emergence of a hierarchical and modular leadership network. All individuals in the model try, with varying degrees of ability, to find a direction of movement, with the result that leader-follower relationships evolve between them, since they tend to follow the more successful ones. The harem-forming ambitions of male individuals inspired by an observed Przewalski horse herd (Hortob\\'agy, Hungary) leads to modular structure. In this approach we find that the harem-leader to harem-member ratio observed in horses corresponds to an optimal network regarding common success, and that modularly structured hierarchy is more benefical than a non-modular one, in the sense that common success is higher, and the underlying network is more hierarchical. We al...

  12. Hypoxic preconditioning in an autohypoxic animal model

    Institute of Scientific and Technical Information of China (English)

    Guo Shao; Guo-Wei Lu

    2012-01-01

    Hypoxic preconditioning refers to the exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that [Results]in increased resistance to a subsequent episode of severe hypoxia/ischemia.In this article,we review recent research based on a mouse model of repeated exposure to autohypoxia.Pre-exposure markedly increases the tolerance to or protection against hypoxic insult,and preserves the cellular structure of the brain.Furthermore,the hippocampal activity amplitude and frequency of electroencephalogram,latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease,while spatial learning and memory improve.In the brain,detrimental neurochemicals such as free radicals are down-regulated,while beneficial ones such as adenosine are upregulated.Also,antihypoxia factor(s) and gene(s) are activated.We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades.A potential path for further research is the development of devices and pharmaceuticals acting on antihypoxia factor(s) and gene(s) for the prevention and treatment of hypoxia and related syndromes.

  13. Transcription factors in pancreatic development. Animal models.

    Science.gov (United States)

    Martin, Merce; Hauer, Viviane; Messmer, Mélanie; Orvain, Christophe; Gradwohl, Gérard

    2007-01-01

    Through the analysis of genetically modified mice a hierarchy of transcription factors regulating pancreas specification, endocrine destiny as well as endocrine subtype specification and differentiation has been established. In addition to conventional approaches such as transgenic technologies and gene targeting, recombinase fate mapping in mice has been key in establishing the lineage relationship between progenitor cells and their progeny in understanding pancreas formation. Moreover, the design of specific mouse models to conditionally express transcription factors in different populations of progenitor cells has revealed to what extent transcription factors required for islet cell development are also sufficient to induce endocrine differentiation and the importance of the competence of progenitor cells to respond to the genetic program implemented by these factors. Taking advantage of this basic science knowledge acquired in rodents, immature insulin-producing cells have recently been differentiated in vitro from human embryonic stem cells. Taken together these major advances emphasize the need to gain further in-depth knowledge of the molecular and cellular mechanisms controlling beta-cell differentiation in mice to generate functional beta-cells in the future that could be used for cell therapy in diabetes. PMID:17923766

  14. 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...

  15. 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.

  16. Animal models of Parkinson's disease and their applications

    Directory of Open Access Journals (Sweden)

    Park HJ

    2016-07-01

    Full Text Available Hyun Jin Park, Ting Ting Zhao, Myung Koo LeeDepartment of Pharmacy, Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea Abstract: Parkinson's disease (PD is a progressive neurodegenerative disorder that occurs mainly due to the degeneration of dopaminergic neuronal cells in the substantia nigra. l-3,4-Dihydroxyphenylalanine (L-DOPA is the most effective known therapy for PD. However, chronic L-DOPA administration results in a loss of drug efficacy and irreversible adverse effects, including L-DOPA-induced dyskinesia, affective disorders, and cognitive function disorders. To study the motor and non-motor symptomatic dysfunctions in PD, neurotoxin and genetic animal models of PD have been widely applied. However, these animal models do not exhibit all of the pathophysiological symptoms of PD. Regardless, neurotoxin rat and mouse models of PD have been commonly used in the development of bioactive components from natural herbal medicines. Here, the main animal models of PD and their applications have been introduced in order to aid the development of therapeutic and adjuvant agents. Keywords: Parkinson's disease, neurotoxin animal models, genetic animal models, adjuvant therapeutics

  17. Animals

    Institute of Scientific and Technical Information of China (English)

    杨光

    2000-01-01

    The largest animal ever to live on the earth is the blue whale(蓝鲸)It weighs about 80 tons--more than 24 elephants. It is more than 30 metres long. A newborn baby whale weighs as much as a big elephant.

  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. Rheology-based facial animation realistic face model

    Institute of Scientific and Technical Information of China (English)

    ZENG Dan; PEI Li

    2009-01-01

    This paper presents a rheology-based approach to animate realistic face model. The dynamic and biorheological characteristics of the force member (muscles) and stressed member (face) are considered. The stressed face can be modeled as viscoelastic bodies with the Hooke bodies and Newton bodies connected in a composite series-parallel manner. Then, the stress-strain relationship is derived, and the constitutive equations established. Using these constitutive equations, the face model can be animated with the force generated by muscles. Experimental results show that this method can realistically simulate the mechanical properties and motion characteristics of human face, and performance of this method is satisfactory.

  20. Immunology of fungal infections: lessons learned from animal models.

    Science.gov (United States)

    Steele, Chad; Wormley, Floyd L

    2012-08-01

    The continuing AIDS epidemic coupled with increased usage of immunosuppressive drugs to prevent organ rejection or treat autoimmune diseases has resulted in an increase in individuals at risk for acquiring fungal diseases. These concerns highlight the need to elucidate mechanisms of inducing protective immune responses against fungal pathogens. Consequently, several experimental models of human mycoses have been developed to study these diseases. The availability of transgenic animal models allows for in-depth analysis of specific components, receptors, and signaling pathways that elicit protection against fungal diseases. This review focuses on recent advances in our understanding of immune responses to fungal infections gained using animal models.

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

    Directory of Open Access Journals (Sweden)

    SONAL eGOSWAMI

    2013-05-01

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

  2. An improved animal model of orthotopic liver transplantation in swine

    Institute of Scientific and Technical Information of China (English)

    ZHENG Shu-guo; DONG Jia-hong; LENG Jian-jun; FENG Xiao-bin; MA Zheng-wei; YAN Yi

    2005-01-01

    Objective: To establish a swine model of orthotopic liver transplantation (OLT) which has high standardization, superior reproducibility and stability. Methods: The rate of success, reproducibility and stability were investigated on the modification of OLTs in closed miniature swine with series of improvements. Results: 20 OLTs were performed on the basis of improvements in experimental animals,surgical procedures and operative monitorings. The mean operation time and anhepatic phase was (181±25.8) and (28.43.2) min respectively, which were significantly shorter than those of the previous re ports. Liver function of the animals recovered shortly after operation. One-week survival rate was 90%,and 15 animals survived more than 1 month. The incidence of vascular and biliary complications was lower in animals with long-term survival. Conclusion: The improved animal model of OLTs in swine is easy to operate with high standardization and rate of success, superior reproducibility and stability. It is an ideal model for series studies related to liver transplantation in big animals.

  3. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    Directory of Open Access Journals (Sweden)

    Priyank Ashok Shenoy

    2016-08-01

    Full Text Available The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  4. Animal models of GM2 gangliosidosis: utility and limitations

    Directory of Open Access Journals (Sweden)

    Lawson CA

    2016-07-01

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

  5. 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

  6. A novel animal model for skin flap prelamination with biomaterials

    Science.gov (United States)

    Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun

    2016-01-01

    Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible. PMID:27659066

  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. ANIMALS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Mammals(哺乳动物)Mammals are the world's most dominant(最占优势的)animal.They are extremely(非常)diverse(多种多样的)creatures(生物,动物)that include(包括)the biggest ever animal (the blue whale鲸,which eats up to 6 tons every day),the smallest(leaf-nosed bat小蹄蝠) and the laziest(sloth树獭,who spends 80% of their time sleeping).There are over 4,600 kinds of mammals and they live in very different environments(环境)—oceans(海洋),rivers,the jungle(丛林),deserts,and plains(平原).

  9. 13A. Integrative Cancer Care: The Life Over Cancer Model

    OpenAIRE

    Block, Keith; Block, Penny; Gyllenhaal, Charlotte; Shoham, Jacob

    2013-01-01

    Focus Areas: Integrative Algorithms of Care Integrative cancer treatment fully blends conventional cancer treatment with integrative therapies such as diet, supplements, exercise and biobehavioral approaches. The Life Over Cancer model comprises three spheres of intervention: improving lifestyle, improving biochemical environment (terrain), and improving tolerance of conventional treatment. These levels are applied within the context of a life-affirming approach to cancer patients and treatme...

  10. GEMMs as preclinical models for testing pancreatic cancer therapies

    OpenAIRE

    Aarthi Gopinathan; Morton, Jennifer P.; Jodrell, Duncan I.; Owen J. Sansom

    2015-01-01

    ABSTRACT Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the fi...

  11. Computer simulation models are implementable as replacements for animal experiments.

    Science.gov (United States)

    Badyal, Dinesh K; Modgill, Vikas; Kaur, Jasleen

    2009-04-01

    It has become increasingly difficult to perform animal experiments, because of issues related to the procurement of animals, and strict regulations and ethical issues related to their use. As a result, it is felt that the teaching of pharmacology should be more clinically oriented and that unnecessary animal experimentation should be avoided. Although a number of computer simulation models (CSMs) are available, they are not being widely used. Interactive demonstrations were conducted to encourage the departmental faculty to use CSMs. Four different animal experiments were selected, that dealt with actions of autonomic drugs. The students observed demonstrations of animal experiments involving conventional methods and the use of CSMs. This was followed by hands-on experience of the same experiment, but using CSMs in small groups, instead of hands-on experience with the animal procedures. Test scores and feedback showed that there was better understanding of the mechanisms of action of the drugs, gained in a shorter time. The majority of the students found the teaching programme used to be good to excellent. CSMs can be used repeatedly and independently by students, and this avoids unnecessary experimentation and also causing pain and trauma to animals. The CSM programme can be implemented in existing teaching schedules for pharmacology undergraduate teaching with basic infrastructure support, and is readily adaptable for use by other institutes. PMID:19453215

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

    Science.gov (United States)

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

    2013-10-01

    Cardiac autonomic neuropathy (CAN) is a relatively common and often devastating complication of diabetes. The major clinical signs are tachycardia, exercise intolerance, and orthostatic hypotension, but the most severe aspects of this complication are high rates of cardiac events and mortality. One of the earliest manifestations of CAN is reduced heart rate variability, and detection of this, along with abnormal results in postural blood pressure testing and/or the Valsalva maneuver, are central to diagnosis of the disease. The treatment options for CAN, beyond glycemic control, are extremely limited and lack evidence of efficacy. The underlying molecular mechanisms are also poorly understood. Thus, CAN is associated with a poor prognosis and there is a compelling need for research to understand, prevent, and reverse CAN. In this review of the literature we examine the use and usefulness of animal models of CAN in diabetes. Compared to other diabetic complications, the number of animal studies of CAN is very low. The published studies range across a variety of species, methods of inducing diabetes, and timescales examined, leading to high variability in study outcomes. The lack of well-characterized animal models makes it difficult to judge the relevance of these models to the human disease. One major advantage of animal studies is the ability to probe underlying molecular mechanisms, and the limited numbers of mechanistic studies conducted to date are outlined. Thus, while animal models of CAN in diabetes are crucial to better understanding and development of therapies, they are currently under-used. PMID:23562143

  13. Amphibians as animal models for laboratory research in physiology.

    Science.gov (United States)

    Burggren, Warren W; Warburton, Stephen

    2007-01-01

    The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."

  14. Rabbit as an animal model for experimental research

    Directory of Open Access Journals (Sweden)

    Manjeet Mapara

    2012-01-01

    Full Text Available Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. Though experimentation on rabbits seems to be easy there are many pitfalls. Our endeavor in this article is to integrate all the data about maintaining rabbits as a model and to critically analyze it on the basis of our experimentation.

  15. Engineering Large Animal Species to Model Human Diseases.

    Science.gov (United States)

    Rogers, Christopher S

    2016-01-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. PMID:27367161

  16. Animal products, calcium and protein and prostate cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Schuurman, A.G.; Brandt, P.A. van den; Dorant, E.; Goldbohm, R.A.

    1999-01-01

    Prostate cancer risk in relation to consumption of animal products, and intake of calcium and protein was investigated in the Netherlands Cohort Study. At baseline in 1986, 58,279 men aged 55-69 years completed a self-administered 150-item food frequency questionnaire and a questionnaire on other ri

  17. Continuous-time discrete-space models for animal movement

    Science.gov (United States)

    Hanks, Ephraim M.; Hooten, Mevin B.; Alldredge, Mat W.

    2015-01-01

    The processes influencing animal movement and resource selection are complex and varied. Past efforts to model behavioral changes over time used Bayesian statistical models with variable parameter space, such as reversible-jump Markov chain Monte Carlo approaches, which are computationally demanding and inaccessible to many practitioners. We present a continuous-time discrete-space (CTDS) model of animal movement that can be fit using standard generalized linear modeling (GLM) methods. This CTDS approach allows for the joint modeling of location-based as well as directional drivers of movement. Changing behavior over time is modeled using a varying-coefficient framework which maintains the computational simplicity of a GLM approach, and variable selection is accomplished using a group lasso penalty. We apply our approach to a study of two mountain lions (Puma concolor) in Colorado, USA.

  18. Rhythm and blues: animal models of epilepsy and depression comorbidity.

    Science.gov (United States)

    Epps, S Alisha; Weinshenker, David

    2013-01-15

    Clinical evidence shows a strong, bidirectional comorbidity between depression and epilepsy that is associated with decreased quality of life and responsivity to pharmacotherapies. At present, the neurobiological underpinnings of this comorbidity remain hazy. To complicate matters, anticonvulsant drugs can cause mood disturbances, while antidepressant drugs can lower seizure threshold, making it difficult to treat patients suffering from both depression and epilepsy. Animal models have been created to untangle the mechanisms behind the relationship between these disorders and to serve as screening tools for new therapies targeted to treat both simultaneously. These animal models are based on chemical interventions (e.g. pentylenetetrazol, kainic acid, pilocarpine), electrical stimulations (e.g. kindling, electroshock), and genetic/selective breeding paradigms (e.g. genetically epilepsy-prone rats (GEPRs), genetic absence epilepsy rat from Strasbourg (GAERS), WAG/Rij rats, swim lo-active rats (SwLo)). Studies on these animal models point to some potential mechanisms that could explain epilepsy and depression comorbidity, such as various components of the dopaminergic, noradrenergic, serotonergic, and GABAergic systems, as well as key brain regions, like the amygdala and hippocampus. These models have also been used to screen possible therapies. The purpose of the present review is to highlight the importance of animal models in research on comorbid epilepsy and depression and to explore the contributions of these models to our understanding of the mechanisms and potential treatments for these disorders.

  19. Animal models of obsessive–compulsive disorder: utility and limitations

    Directory of Open Access Journals (Sweden)

    Alonso P

    2015-08-01

    Full Text Available Pino Alonso,1–4 Clara López-Solà,1–3 Eva Real,1–3 Cinto Segalàs,1–3 José Manuel Menchón1–41OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, 2Bellvitge Biomedical Research Institute-IDIBELL, 3Centro de Investigación en Red de Salud Mental, Carlos III Health Institute, 4Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, SpainAbstract: Obsessive–compulsive disorder (OCD is a disabling and common neuropsychiatric condition of poorly known etiology. Many attempts have been made in the last few years to develop animal models of OCD with the aim of clarifying the genetic, neurochemical, and neuroanatomical basis of the disorder, as well as of developing novel pharmacological and neurosurgical treatments that may help to improve the prognosis of the illness. The latter goal is particularly important given that around 40% of patients with OCD do not respond to currently available therapies. This article summarizes strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity. On the basis of this evaluation, we discuss that currently labeled “animal models of OCD” should be regarded not as models of OCD but, rather, as animal models of different psychopathological processes, such as compulsivity, stereotypy, or perseverance, that are present not only in OCD but also in other psychiatric or neurological disorders. Animal models might constitute a challenging approach to study the neural and genetic mechanism of these phenomena from a trans-diagnostic perspective. Animal models are also of particular interest as tools for developing new therapeutic options for OCD, with the greatest convergence focusing on the glutamatergic system, the role of ovarian and related hormones, and the exploration of new

  20. HCV Animal Models: A Journey of More than 30 Years

    Directory of Open Access Journals (Sweden)

    Philip Meuleman

    2009-09-01

    Full Text Available In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV was discovered and found to be the major causative agent of these infections. Because of its narrow ropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV.

  1. HCV animal models: a journey of more than 30 years.

    Science.gov (United States)

    Meuleman, Philip; Leroux-Roels, Geert

    2009-09-01

    In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow tropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV. PMID:21994547

  2. Large Animal Models of Neurological Disorders for Gene Therapy

    OpenAIRE

    Gagliardi, Christine; Bunnell, Bruce A.

    2009-01-01

    The development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological diso...

  3. Computational physics : a modeler-simulator for animated physical objects

    OpenAIRE

    Luciani, Annie; Jimenez, Stéphane; Florens, Jean-Loup; Cadoz, Claude; Raoult, Olivier

    1991-01-01

    International audience Physical modeling for animation is now firmly established. The present aim is to design and build a structured and well-defined tool rather merely specific algorithms to simulate physical knowledge. We will first define the basic functions of a modeler-simulator for physical modeling which enables operator gestural control, and where the simulation processes are real time oriented. We will then introduce the Cordis-Anima system, its constructive language, its real ti...

  4. The Use of Animal Models for Stroke Research: A Review

    OpenAIRE

    Juliana B Casals; Pieri, Naira CG; Feitosa, Matheus LT; Ercolin, Anna CM; Roballo, Kelly CS; Barreto, Rodrigo SN; Bressan, Fabiana F; Daniele S. Martins; Maria A. Miglino; Carlos E. Ambrósio

    2011-01-01

    Stroke has been identified as the second leading cause of death worldwide. Stroke is a focal neurologic deficit caused by a change in cerebral circulation. The use of animal models in recent years has improved our understanding of the physiopathology of this disease. Rats and mice are the most commonly used stroke models, but the demand for larger models, such as rabbits and even nonhuman primates, is increasing so as to better understand the disease and its treatment. Although the basic mech...

  5. Relevance of animal models to human tardive dyskinesia

    OpenAIRE

    Blanchet Pierre J; Parent Marie-Thérèse; Rompré Pierre H; Lévesque Daniel

    2012-01-01

    Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain suscepti...

  6. Predictive validity of behavioural animal models for chronic pain

    OpenAIRE

    Berge, Odd-Geir

    2011-01-01

    Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between precl...

  7. Animal models and brain circuits in drug addiction.

    Science.gov (United States)

    Kalivas, Peter W; Peters, Jamie; Knackstedt, Lori

    2006-12-01

    Animal models in the field of addiction are considered to be among the best available models of neuropsychiatric disease. These models have undergone a number of refinements that allow deeper understanding of the circuitry involved in initiating drug seeking and relapse. Notably, the demonstrable involvement of classic corticostriatal habit circuitry and the engagement of prefrontal cortical circuits in extinction training may have relevance to the therapeutic modulation of habit circuitry and drug addiction in humans. PMID:17200461

  8. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

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

    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. PMID:26415576

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    both 7 and 28 days. Conclusion: It was possible to create a healed but weak abdominal fascia in rats with a minimum of defects after incision using a running suture technique in the fascia. In contrast to other models, regular tissue defects were absent, and the model can therefore be used to evaluate......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...... 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...

  10. Combining Spatial and Telemetric Features for Learning Animal Movement Models

    CERN Document Server

    Kapicioglu, Berk; Wikelski, Martin; Broderick, Tamara

    2012-01-01

    We introduce a new graphical model for tracking radio-tagged animals and learning their movement patterns. The model provides a principled way to combine radio telemetry data with an arbitrary set of userdefined, spatial features. We describe an efficient stochastic gradient algorithm for fitting model parameters to data and demonstrate its effectiveness via asymptotic analysis and synthetic experiments. We also apply our model to real datasets, and show that it outperforms the most popular radio telemetry software package used in ecology. We conclude that integration of different data sources under a single statistical framework, coupled with appropriate parameter and state estimation procedures, produces both accurate location estimates and an interpretable statistical model of animal movement.

  11. Animal models for implant biomaterial research in bone: A review

    Directory of Open Access Journals (Sweden)

    A I Pearce

    2007-03-01

    Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.

  12. Investigation of nutriactive phytochemical - gamma-oryzanol in experimental animal models.

    Science.gov (United States)

    Szcześniak, K A; Ostaszewski, P; Ciecierska, A; Sadkowski, T

    2016-08-01

    Gamma-oryzanol (GO) is an abundant dietary antioxidant that is considered to have beneficial effects in cardiovascular disease, cancer and diabetes. Other potential properties of GO include inhibition of gastric acid secretion and decreased post-exercise muscle fatigue. GO is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil, a byproduct of rice processing. GO has been studied by many researchers over the last three decades. In particular, the utility of GO supplementation has been documented in numerous animal models. A large variety of species was examined, and various experimental methodologies and targets were applied. The aim of this study was to summarize the body of research on GO supplementation in animals and to examine possible mechanisms of GO action. Furthermore, while the safety of GO supplementation in animals has been well documented, studies demonstrating pharmacokinetics, pharmacodynamics and efficiency are less clear. The observed differences in these findings are also discussed. PMID:26718022

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

    International Nuclear Information System (INIS)

    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

  14. Principles for developing animal models of military PTSD

    Directory of Open Access Journals (Sweden)

    Nikolaos P. Daskalakis

    2014-08-01

    Full Text Available The extent to which animal studies can be relevant to military posttraumatic stress disorder (PTSD continues to be a matter of discussion. Some features of the clinical syndrome are more easily modeled than others. In the animal literature, a great deal of attention is focused on modeling the characteristics of military exposures and their impact on measurable behaviors and biological parameters. There are many issues to consider regarding the ecological validity of predator, social defeat or immobilization stress to combat-related experience. In contrast, less attention has been paid to individual variation following these exposures. Such variation is critical to understand how individual differences in the response to military trauma exposure may result to PTSD or resilience. It is important to consider potential differences in biological findings when comparing extremely exposed to non-exposed animals, versus those that result from examining individual differences. Animal models of military PTSD are also critical in advancing efforts in clinical treatment. In an ideal translational approach to study deployment related outcomes, information from humans and animals, blood and brain, should be carefully considered in tandem, possibly even computed simultaneously, to identify molecules, pathways and networks that are likely to be the key drivers of military PTSD symptoms. With the use novel biological methodologies (e.g., optogenetics in the animal models, critical genes and pathways can be tuned up or down (rather than over-expressed or ablated completely in discrete brain regions. Such techniques together with pre-and post-deployment human imaging will accelerate the identification of novel pharmacological and non-pharmacological intervention strategies.

  15. Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues.

    OpenAIRE

    Zaloudik, J; Basak, S.; Nesbit, M.; Speicher, D W; Wunner, W H; Miller, E.; Ernst-Grotkowski, C.; Kennedy, R; Bergsagel, L. P.; Koido, T.; Herlyn, D

    1997-01-01

    The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on...

  16. Infectious diseases among animals : combining models with data

    NARCIS (Netherlands)

    Koeijer, A.A. de

    2003-01-01

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

  17. 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...

  18. Airway Strain during Mechanical Ventilation in an Intact Animal Model

    OpenAIRE

    Sinclair, Scott E.; Molthen, Robert C.; Haworth, Steve T.; Dawson, Christopher A.; Waters, Christopher M.

    2007-01-01

    Rationale: Mechanical ventilation with large tidal volumes causes ventilator-induced lung injury in animal models. Little direct evidence exists regarding the deformation of airways in vivo during mechanical ventilation, or in the presence of positive end-expiratory pressure (PEEP).

  19. An Aerosolized Brucella spp. Challenge Model for Laboratory Animals

    Science.gov (United States)

    To characterize the optimal aerosol dosage of Brucella abortus strain 2308 (S2308) and B. melitensis (S16M) in a laboratory animal model of brucellosis, dosages of 10**3 to 10**10 CFU were nebulized to mice. Although tissue weights were minimally influenced, total colony-forming units (CFU) per tis...

  20. Animal models of cerebral ischemia for evaluation of drugs.

    Science.gov (United States)

    Gupta, Y K; Briyal, Seema

    2004-10-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Brain attack is a term introduced to describe the acute presentation of stroke, which emphasizes the need for urgent action to remedy the situation. Though a large number of therapeutic agents like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or being evaluated, there remains a large gap between the benefits by these agents and properties an ideal drug for stroke should offer. In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke. For better evaluation of the drugs and enhancement of their predictability from animal experimentation to clinical settings, it has been realized that the selection of animal models, the parameters to be evaluated should be critically assessed. Focal and global cerebral ischemia represents diseases that are common in the human population. Understanding the mechanisms of injury and neuroprotection in these diseases is important to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. In this article we attempted to summarize commonly explored animal models of focal and global cerebral ischemia and evaluate their advantages and limitations. PMID:15907047

  1. Animation Model to Conceptualize ATP Generation: A Mitochondrial Oxidative Phosphorylation

    Science.gov (United States)

    Jena, Ananta Kumar

    2015-01-01

    Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…

  2. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    R.A. Bem; J.B. Domachowske; H.F. Rosenberg

    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 n

  3. The motivations and methodology for high-throughput PET imaging of small animals in cancer research

    International Nuclear Information System (INIS)

    Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed. (orig.)

  4. The motivations and methodology for high-throughput PET imaging of small animals in cancer research

    Energy Technology Data Exchange (ETDEWEB)

    Aide, Nicolas [Francois Baclesse Cancer Centre, Nuclear Medicine Department, Caen Cedex (France); Caen University, BioTICLA team, EA 4656, IFR 146, Caen (France); Visser, Eric P. [Radboud University Nijmegen Medical Center, Nuclear Medicine Department, Nijmegen (Netherlands); Lheureux, Stephanie [Caen University, BioTICLA team, EA 4656, IFR 146, Caen (France); Francois Baclesse Cancer Centre, Clinical Research Unit, Caen (France); Heutte, Natacha [Francois Baclesse Cancer Centre, Clinical Research Unit, Caen (France); Szanda, Istvan [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, East Melbourne (Australia)

    2012-09-15

    Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed. (orig.)

  5. 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.

  6. Serotonergic pharmacology in animal models: from behavioral disorders to dyskinesia.

    Science.gov (United States)

    Beaudoin-Gobert, Maude; Sgambato-Faure, Véronique

    2014-06-01

    Serotonin (5-HT) dysfunction has been involved in both movement and behavioral disorders. Serotonin pharmacology improves dyskinetic movements as well as depressive, anxious, aggressive and anorexic symptoms. Animal models have been useful to investigate more precisely to what extent 5-HT is involved and whether drugs targeting the 5-HT system can counteract the symptoms exhibited. We review existing rodent and non-human primate (NHP) animal models in which selective 5-HT or dual 5-HT-norepinephrine (NE) transporter inhibitors, as well as specific 5-HT receptors agonists and antagonists, monoamine oxidase A inhibitors (IMAO-A) and MDMA (Ecstasy) have been used. We review overlaps between the various drug classes involved. We confront behavioral paradigms and treatment regimen. Some but not all animal models and associated pharmacological treatments have been extensively studied in the litterature. In particular, the impact of selective serotonin reuptake inhibitors (SSRI) has been extensively investigated using a variety of pharmacological or genetic rodent models of depression, anxiety, aggressiveness. But the validity of these rodent models is questioned. On the contrary, few studies did address the potential impact of targeting the 5-HT system on NHP models of behavioral disorders, despite the fact that those models may match more closely to human pathologies. Further investigations with carefull behavioral analysis will improve our understanding of neural bases underlying the pathophysiology of movement and behavioral disorders. PMID:24486710

  7. A systematic review of animal models for experimental neuroma.

    Science.gov (United States)

    Toia, Francesca; Giesen, Thomas; Giovanoli, Pietro; Calcagni, Maurizio

    2015-10-01

    Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be defined. Experimental research still plays a major role, but - although numerous neuroma models have been proposed on different animals - there is still no single model recognised as being the reference. Several models show advantages over the others in specific aspects of neuroma physiopathology, prevention or treatment, making it unlikely that a single model could be of reference. A reproducible and standardised model of peripheral neuroma would allow better comparison of results from different studies. We present a systematic review of the literature on experimental in vivo models, analysing advantages and disadvantages, specific features and indications, with the goal of providing suggestions to help their standardisation. Published models greatly differ in the animal and the nerve employed, the mechanisms of nerve injury and the evaluation methods. Specific experimental models exist for terminal neuromas and neuromas in continuity (NIC). The rat is the most widely employed animal, the rabbit being the second most popular model. NIC models are more actively researched, but it is more difficult to generate such studies in a reproducible manner. Nerve transection is considered the best method to cause terminal neuromas, whereas partial transection is the best method to cause NIC. Traditional histomorphology is the historical gold-standard evaluation method, but immunolabelling, reverse transcriptase-polymerase chain reaction (RT-PCR) and proteomics are gaining increasing popularity. Computerised gait analysis is the gold standard for motor-recovery evaluation, whereas mechanical testing of allodynia and hyperalgesia reproducibly assesses sensory recovery. This review summarises current knowledge on experimental neuroma models, and it provides a useful tool for defining experimental protocols

  8. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-11-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

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

    Science.gov (United States)

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

    2015-09-01

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

  10. An Animal Model of Emotional Blunting in Schizophrenia

    OpenAIRE

    Pietersen, Charmaine Y.; Fokko J Bosker; Janine Doorduin; Jongsma, Minke E.; Folkert Postema; Joseph V Haas; Johnson, Michael P; Tineke Koch; Tony Vladusich; den Boer, Johan A.

    2007-01-01

    Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rat...

  11. Large Animal Models for Batten Disease: A Review

    OpenAIRE

    Weber, Krystal; Pearce, David A.

    2013-01-01

    The neuronal ceroid lipofuscinoses, collectively referred to as Batten disease, make up a group of inherited childhood disorders that result in blindness, motor and cognitive regression, brain atrophy, and seizures, ultimately leading to premature death. So far more than 10 genes have been implicated in different forms of the neuronal ceroid lipofuscinoses. Most related research has involved mouse models, but several naturally occurring large animal models have recently been discovered. In th...

  12. Continuum modeling of the equilibrium and stability of animal flocks

    OpenAIRE

    Mecholsky, Nicholas A.; Ott, Edward; Antonsen Jr., Thomas M.; Guzdar, Parvez

    2012-01-01

    Groups of animals often tend to arrange themselves in flocks that have characteristic spatial attributes and temporal dynamics. Using a dynamic continuum model for a flock of individuals, we find equilibria of finite spatial extent where the density goes continuously to zero at a well-defined flock edge, and we discuss conditions on the model that allow for such solutions. We also demonstrate conditions under which, as the flock size increases, the interior density in our equilibria tends to ...

  13. A Knowledge Representation Model for Video—Based Animation

    Institute of Scientific and Technical Information of China (English)

    劳志强; 潘云鹤

    1998-01-01

    In this paper,a brief survey on knowledge-based animation techniques is given.Then a VideoStream-based Knowledge Representation Model(VSKRM)for Joint Objects is presented which includes the knowledge representation of :Graphic Object,Action and VideoStream.Next a general description of the UI framework of a system is given based on the VSKRM model.Finally,a conclusion is reached.

  14. Improved Animal Models for Testing Gene Therapy for Atherosclerosis

    OpenAIRE

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

    2013-01-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike le...

  15. Mechanobiology of Embryonic Skeletal Development: Insights from Animal Models

    OpenAIRE

    Nowlan, Niamh C.; Sharpe, James; Karen A Roddy; Prendergast, Patrick J; Murphy, Paula

    2010-01-01

    A range of clinical conditions in which foetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, in particular the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, while genetically modified mice with non-functional o...

  16. Animal models of restricted repetitive behavior in autism

    OpenAIRE

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

    2006-01-01

    Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather t...

  17. Tissue and Animal Models of Sudden Cardiac Death

    OpenAIRE

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Steven R. Houser; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expressi...

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

    OpenAIRE

    Abelaira, Helena M.; Gislaine Z. Reus; Joao Quevedo

    2013-01-01

    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...

  19. Functional GI disorders: from animal models to drug development

    OpenAIRE

    Mayer, E A; Bradesi, S; Chang, L; Spiegel, B. M. R.; Bueller, J A; Naliboff, B. D.

    2007-01-01

    Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacological treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly standard algorithm using animal models, experimental medicine models and clinical trials. In the current articl...

  20. The Cambridge MRI database for animal models of Huntington disease.

    Science.gov (United States)

    Sawiak, Stephen J; Morton, A Jennifer

    2016-01-01

    We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.

  1. Bayesian modeling of animal- and herd-level prevalences.

    Science.gov (United States)

    Branscum, A J; Gardner, I A; Johnson, W O

    2004-12-15

    We reviewed Bayesian approaches for animal-level and herd-level prevalence estimation based on cross-sectional sampling designs and demonstrated fitting of these models using the WinBUGS software. We considered estimation of infection prevalence based on use of a single diagnostic test applied to a single herd with binomial and hypergeometric sampling. We then considered multiple herds under binomial sampling with the primary goal of estimating the prevalence distribution and the proportion of infected herds. A new model is presented that can be used to estimate the herd-level prevalence in a region, including the posterior probability that all herds are non-infected. Using this model, inferences for the distribution of prevalences, mean prevalence in the region, and predicted prevalence of herds in the region (including the predicted probability of zero prevalence) are also available. In the models presented, both animal- and herd-level prevalences are modeled as mixture distributions to allow for zero infection prevalences. (If mixture models for the prevalences were not used, prevalence estimates might be artificially inflated, especially in herds and regions with low or zero prevalence.) Finally, we considered estimation of animal-level prevalence based on pooled samples. PMID:15579338

  2. Peripheral Biomarkers in Animal Models of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Lucia Carboni

    2013-01-01

    Full Text Available Investigations of preclinical biomarkers for major depressive disorder (MDD encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

  3. Peripheral biomarkers in animal models of major depressive disorder.

    Science.gov (United States)

    Carboni, Lucia

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets. PMID:24167347

  4. Malarial birds: modeling infectious human disease in animals.

    Science.gov (United States)

    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  5. A retrospective investigation on canine papillomavirus 1 (CPV1 in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer.

    Directory of Open Access Journals (Sweden)

    Ilaria Porcellato

    Full Text Available CPV1 (also called COPV is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs, but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas and 10 hyperplastic lesions (gingival hyperplasia were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10% SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

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

    International Nuclear Information System (INIS)

    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

  7. 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.

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

    Science.gov (United States)

    Wang, Ya-Fang; Yu, Chun-Keung

    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

  9. Making animals alcoholic: shifting laboratory models of addiction.

    Science.gov (United States)

    Ramsden, Edmund

    2015-01-01

    The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field. PMID:25740698

  10. 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. PMID:25048261

  11. Reproduction of an animal model of landmine blast injuries

    Directory of Open Access Journals (Sweden)

    Sen ZHANG

    2014-03-01

    Full Text Available Objective To reproduce an animal model of landmine blast injuries for studying its mechanism and characteristics. Methods Fifteen healthy New Zealand white rabbits (body weight 1.9-2.4 kg were prepared as experimental animals. Punctiform burster was used to simulate the landmine, and it was electrically detonated far away to produce landmine blast injuries on unilateral hind limb of rabbits in upright state. The vital signs before and 5min, 15min, 30min, 45min, 1h, 2h, 3h, 6h, 9h and 12h after injuries were recorded. Autopsy of dead animals was performed immediately and the survivors were sacrificed for pathological examination 6h and 12h after the injury. Macroscopic and microscopic changes in the injured limb and distant organs were observed. Fifteen random adult body weights were generated by random number table, and the explosive energy of M14 landmine (about 29g TNT explosive energy was simulated, to compare the ratio of explosive force equivalent to weight calculated between experimental animals and randomly selected adults. Results No significant change in blood pressure was observed at different time points before and after injuries. A broom-like change was found in the injured limb by the general observation. The subareas and pathological changes of injured limb coincided with the typical limb injuries produced by landmine explosion. Damage in different degrees was found in distant organs, and the wound characteristics and injury of major organs were in accordance with the reports of relevant literature. The ratio of explosive equivalent to weight of experimental animals (0.50±0.04g TNT/kg was similar to that of randomly selected adults (0.51±0.05g TNT/kg. Conclusion The present animal model could simulate the landmine explosive injuries, and may be used in research of landmine explosive injuries. DOI: 10.11855/j.issn.0577-7402.2014.01.14

  12. Treatment of bovine cancer-eye (and other animal tumors) with heat

    International Nuclear Information System (INIS)

    Hyperthermia appears to be an excellent technique for the treatment of a variety of animal tumors. While this report has emphasized the application of hyperthermia to bovine cancer-eye, there cannot be serious doubt about the potential for wider applications of the technique. We have collaborated with the Animal Resource Facility at the University of New Mexico in the successful treatment of a variety of tumors in small animals which would not be a particular interest to stockmen, but the program included the successful treatment of a number of sarcoids in horses. This investigation involving heat effects on sarcoids will continue, but early results appear to be promising. Other veterinarians are using the commercial hyperthermia instruments to treat a variety of small-animal tumors; these practitioners are enthusiastic about the results but no data have been published to date. We have treated an equine lid tumor with good results, and others are pursuing investigations in this area. Use of commercial hyperthermia instruments for treatment of any condition other than bovine cancer-eye or similar small tumors on animals cannot be justified. Like other therapeutic techniques, hyperthermia must be applied to appropriate cases and retreatment will be necessary in some instances

  13. Animal models of antimuscle-specific kinase myasthenia.

    Science.gov (United States)

    Richman, David P; Nishi, Kayoko; Ferns, Michael J; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A; Agius, Mark A

    2012-12-01

    Antimuscle-specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance.

  14. Characterization of animal models for primary sclerosing cholangitis (PSC).

    Science.gov (United States)

    Fickert, Peter; Pollheimer, Marion J; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon; Housset, Chantal; Keitel, Verena; Schramm, Christoph; Marschall, Hanns-Ulrich; Karlsen, Tom H; Melum, Espen; Kaser, Arthur; Eksteen, Bertus; Strazzabosco, Mario; Manns, Michael; Trauner, Michael

    2014-06-01

    Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.

  15. Neuronal and brain morphological changes in animal models of schizophrenia.

    Science.gov (United States)

    Flores, Gonzalo; Morales-Medina, Julio César; Diaz, Alfonso

    2016-03-15

    Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits. PMID:26738967

  16. 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.

  17. Neuronal and brain morphological changes in animal models of schizophrenia.

    Science.gov (United States)

    Flores, Gonzalo; Morales-Medina, Julio César; Diaz, Alfonso

    2016-03-15

    Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits.

  18. Hand Interface in Traditional Modeling and Animation Tasks

    Institute of Scientific and Technical Information of China (English)

    孙汉秋

    1996-01-01

    3-D task space in modeling and animation is usually reduced to the separate control dimensions supported by conventional interactive devices.This limitation maps only partial view of the problem to the device space at a time,and results in tedious and unnatural interface of control.This paper uses the DataGlove interface for modeling and animating scene behaviors.The modeling interface selects,scales,rotates,translates,copies and deletes the instances of the primitives.These basic modeling processes are directly performed in the task space,using hand shapes and motions.Hand shapes are recognized as discrete states that trigger the commands,and hand motion are mapped to the movement of a selected instance.The interactions through hand interface place the user as a participant in the process of behavior simulation.Both event triggering and role switching of hand are experimented in simulation.The event mode of hand triggers control signals or commands through a menu interface.The object mode of hand simulates itself as an object whose appearance or motion influences the motions of other objects in scene.The involvement of hand creates a diversity of dynamic situations for testing variable scene behaviors.Our experiments have shown the potential use of this interface directly in the 3-D modeling and animation task space.

  19. Chemical genetics and drug screening in Drosophila cancer models

    Institute of Scientific and Technical Information of China (English)

    Mara Gladstone; Tin Tin Su

    2011-01-01

    Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety.It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later.In this regard,it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays.Drosophila melanogaster has emerged as a potential whole animal model for drug screening.Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer.A recent review provides a comprehensive summary of drug screening in Drosophila,but with an emphasis on neurodegenerative disorders.Here,we review Drosophila screens in the literature aimed at cancer therapeutics.

  20. Tissue-engineered models of human tumors for cancer research

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  1. Extending animal models of fear conditioning to humans.

    Science.gov (United States)

    Delgado, M R; Olsson, A; Phelps, E A

    2006-07-01

    A goal of fear and anxiety research is to understand how to treat the potentially devastating effects of anxiety disorders in humans. Much of this research utilizes classical fear conditioning, a simple paradigm that has been extensively investigated in animals, helping outline a brain circuitry thought to be responsible for the acquisition, expression and extinction of fear. The findings from non-human animal research have more recently been substantiated and extended in humans, using neuropsychological and neuroimaging methodologies. Research across species concur that the neural correlates of fear conditioning include involvement of the amygdala during all stages of fear learning, and prefrontal areas during the extinction phase. This manuscript reviews how animal models of fear are translated to human behavior, and how some fears are more easily acquired in humans (i.e., social-cultural). Finally, using the knowledge provided by a rich animal literature, we attempt to extend these findings to human models targeted to helping facilitate extinction or abolishment of fears, a trademark of anxiety disorders, by discussing efficacy in modulating the brain circuitry involved in fear conditioning via pharmacological treatments or emotion regulation cognitive strategies. PMID:16472906

  2. Sex Differences in Animal Models: Focus on Addiction.

    Science.gov (United States)

    Becker, Jill B; Koob, George F

    2016-04-01

    The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences.

  3. Sex Differences in Animal Models: Focus on Addiction.

    Science.gov (United States)

    Becker, Jill B; Koob, George F

    2016-04-01

    The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. PMID:26772794

  4. Automated quantitative gait analysis in animal models of movement disorders

    Directory of Open Access Journals (Sweden)

    Vandeputte Caroline

    2010-08-01

    Full Text Available Abstract Background Accurate and reproducible behavioral tests in animal models are of major importance in the development and evaluation of new therapies for central nervous system disease. In this study we investigated for the first time gait parameters of rat models for Parkinson's disease (PD, Huntington's disease (HD and stroke using the Catwalk method, a novel automated gait analysis test. Static and dynamic gait parameters were measured in all animal models, and these data were compared to readouts of established behavioral tests, such as the cylinder test in the PD and stroke rats and the rotarod tests for the HD group. Results Hemiparkinsonian rats were generated by unilateral injection of the neurotoxin 6-hydroxydopamine in the striatum or in the medial forebrain bundle. For Huntington's disease, a transgenic rat model expressing a truncated huntingtin fragment with multiple CAG repeats was used. Thirdly, a stroke model was generated by a photothrombotic induced infarct in the right sensorimotor cortex. We found that multiple gait parameters were significantly altered in all three disease models compared to their respective controls. Behavioural deficits could be efficiently measured using the cylinder test in the PD and stroke animals, and in the case of the PD model, the deficits in gait essentially confirmed results obtained by the cylinder test. However, in the HD model and the stroke model the Catwalk analysis proved more sensitive than the rotarod test and also added new and more detailed information on specific gait parameters. Conclusion The automated quantitative gait analysis test may be a useful tool to study both motor impairment and recovery associated with various neurological motor disorders.

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

    OpenAIRE

    Wang, Ya-Fang; Yu, Chun-Keung

    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 ...

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

    Science.gov (United States)

    Sigurdsson, T

    2016-05-01

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

  7. Microscopic transport model animation visualisation on KML base

    Science.gov (United States)

    Yatskiv, I.; Savrasovs, M.

    2012-10-01

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

  8. WHAT WE ARE LEARNING ON HTLV-1 PATHOGENESISFROM ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    Madeleine eDuc Dodon

    2012-08-01

    Full Text Available Isolated and identified more than 30 years ago, Human T-cell Leukemia Virus type 1 (HTLV-1 is the etiological agent of adult T-cell leukemia/lymphoma (ATL, an aggressive lymphoproliferative disease of activated CD4+ T cells, and other inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. A variety of animal models have contributed to the fundamental knowledge of HTLV-1 transmission, pathogenesis and to the design of novel therapies to treat HTLV-1 associated diseases. Small animal models (rabbits, rats, mice as well as large animal models (monkeys have been utilized to significantly advance characterization of the viral proteins and of virus-infected cells in the early steps of infection, as well as in the development of leukemogenic and immunopathogenic processes. Over the past two decades, the creation of new immuno-compromised mouse strains that are robustly reconstituted with a functional human immune system (HIS after being transplanted with human tissues or progenitor cells has revolutionized the in vivo investigation of viral infection and pathogenesis. Recent observations obtained in HTLV-1-infected humanized HIS mice that develop lymphomas provide the opportunity to study the evolution of the proviral clonality in human T cells present in different lymphoid organs. Current progress in the improvement of those humanized models will favor the testing of drugs and the development of targeted therapies against HTLV-1-associated diseases.

  9. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

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

  10. Large Animal Models for Foamy Virus Vector Gene Therapy

    Directory of Open Access Journals (Sweden)

    Peter A. Horn

    2012-12-01

    Full Text Available Foamy virus (FV vectors have shown great promise for hematopoietic stem cell (HSC gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit.

  11. A database for a meta-analysis of cancer risk in animals at low doses and dose rates of ionising radiation

    International Nuclear Information System (INIS)

    Results of animal experiments listed in the International Radiobiology Archives (I.R.A.), complemented with data published in peer-reviewed literature since 1996 have been assembled in one data base and the induction of cancer at low doses has been analyzed. In total, approximately 100 separate, independent sets of experimental data have been studied. The main objective of this work is to provide information on radiation risk in the 0-500 mGy range. The data analyzed were those for which no significant reduction of life span was observed in exposed animals; or doses did not exceed 1 Gy; or no cancer was observed in exposed animals. With these criteria data sets with organ doses well in excess of 1 Gy were taken into account. In animals with a low natural incidence of cancer, the difference between the observed number of cancer cases and the prediction of the Linear No-threshold (LNT) hypothesis was compared in each experiment. Following intake of alpha emitters, the number of cancers observed is about 60% of the number of number predicted by the LNT, and only about 56% following intake of beta emitters. In some experiments, statistically weak protective effects were observed following the intake of alpha emitters, whereas apparently statistically strong protective effects were observed in some groups of animals exposed to beta radiation. In animals exposed to low LET radiation and neutrons, both clear excess cancer risk and clear cancer deficits were observed. In a second series of analysis, the several modeling approaches were used to model dose-response. Linear, logistic and probit regression models were examined. For all the data sets examined in this work, the analysis of the data using the LOGISTIC model seems to indicate surplus of negative slopes in the dose-response fits. Finer analyses are underway to determine what parameters are common to experiments which display similar dose-response relationships. If they exist in a sufficient number of experiments

  12. The search for animal models for Lassa fever vaccine development.

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

  13. The search for animal models for Lassa fever vaccine development

    Science.gov (United States)

    Lukashevich, Igor S

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

  14. Impaired auditory sensorimotor gating: An animal model of schizophrenia

    Institute of Scientific and Technical Information of China (English)

    LI Liang; SHAO Feng

    2003-01-01

    Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the "protection-of-processing" theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: i ) modulations of neuro- transmission that are closely associated with schizophrenia; ii )focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and iii) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.

  15. Critical Behavior in a Cellular Automata Animal Disease Transmission Model

    CERN Document Server

    Morley, P D; Chang, Julius

    2003-01-01

    Using a cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared on a farm, there is mandatory slaughter (culling) of all livestock on an infected premise (IP). Those farms that neighbor an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor iteractions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The non-local disease transport probability can be as low as .01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fissio...

  16. 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.

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

    Science.gov (United States)

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

    2014-09-26

    Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. PMID:25132362

  18. 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.

  19. Relevance of animal models to human tardive dyskinesia.

    Science.gov (United States)

    Blanchet, Pierre J; Parent, Marie-Thérèse; Rompré, Pierre H; Lévesque, Daniel

    2012-01-01

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

  20. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

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

  1. The mathematics of cancer: integrating quantitative models.

    Science.gov (United States)

    Altrock, Philipp M; Liu, Lin L; Michor, Franziska

    2015-12-01

    Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

  2. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

    Directory of Open Access Journals (Sweden)

    Matthias Edinger

    1999-10-01

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

  3. DIFFERENT ANIMAL MODELS FOR DRUGS WITH POTENTIAL ANTIDIABETIC PROPERTIES

    OpenAIRE

    Shah Tanmay A; Shah Nidhi T; Prajapati Parimal M; Bhatt Pratik B; Solanki Anil S

    2011-01-01

    The increasing worldwide incidence of diabetes mellitus in adults constitutes a global public health burden. It is predicted that by 2030, largest number of people with diabetes. Although medicinal plants have been historically used for diabetes treatment throughout the world, few of them have been validated by scientific criteria. In recent times, an outsized multiplicity of animal models has been developed to enhanced understand the pathogenesis of diabetes mellitus and new drugs have been ...

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

    OpenAIRE

    Jeffery L. Larkin; David S. Maehr; John J. Cox

    2004-01-01

    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 co...

  5. Colony variability under the spotlight in animal models of arthritis

    OpenAIRE

    Robinson, John H.

    2009-01-01

    A recent article by Farkas and colleagues, published in Arthritis Research & Therapy, is from the laboratory of Dr Tibor Glant and his research team in Chicago, who have investigated in considerable depth the immunopathology of experimental arthritis induced by the major cartilage component proteoglycan aggrecan in an animal model that mimics many features of human rheumatoid arthritis and ankylosing spondylitis. This present report takes our understanding a significant step forward by questi...

  6. Are NCAM deficient mice an animal model for schizophrenia?

    OpenAIRE

    Anne eAlbrecht; Oliver eStork

    2012-01-01

    Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we...

  7. Atherosclerosis and Thrombosis: Insights from Large Animal Models

    OpenAIRE

    Gemma Vilahur; Teresa Padro; Lina Badimon

    2011-01-01

    Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protei...

  8. A Review of Translational Animal Models for Knee Osteoarthritis

    OpenAIRE

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

    2012-01-01

    Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are impo...

  9. The search for animal models for Lassa fever vaccine development

    OpenAIRE

    Lukashevich, Igor S.

    2013-01-01

    Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by bioc...

  10. Is Epilepsy a Preventable Disorder? New Evidence from Animal Models

    OpenAIRE

    Giblin, Kathryn A.; Blumenfeld, Hal

    2010-01-01

    Epilepsy accounts for 0.5% of the global burden of disease, and primary prevention of epilepsy represents one of the three 2007 NINDS Epilepsy Research Benchmarks. In the past decade, efforts to understand and intervene in the process of epileptogenesis have yielded fruitful preventative strategies in animal models. This article reviews the current understanding of epileptogenesis, introduces the concept of a “critical period” for epileptogenesis, and examines strategies for epilepsy preventi...

  11. Animal models for implant biomaterial research in bone: A review

    OpenAIRE

    A I Pearce; Richards, R.G; Milz, S.; E. SCHNEIDER; S G Pearce

    2007-01-01

    Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing o...

  12. Animal models of female pelvic organ prolapse: lessons learned

    OpenAIRE

    Couri, Bruna M.; Lenis, Andrew T.; Borazjani, Ali; Paraiso, Marie Fidela R; Damaser, Margot S.

    2012-01-01

    Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. T...

  13. Mathematical modeling for digestible protein in animal feeds for tilapia

    OpenAIRE

    Luiz Vítor Oliveira Vidal; Wilson Massamitu Furuya; Elias Nunes Martins; Tadeu Orlandi Xavier; Mariana Michelato; Themis Sakaguti Graciano

    2012-01-01

    The objective of this study was to formulate mathematical models to estimate digestible protein in some animal feeds for tilapia. Literature results of the proximate composition of crude protein, ether extract, and mineral matter, as well as digestible protein obtained in biological assays, were used. The data were subjected to multiple linear stepwise backward regression. Path analysis was performed to measure the direct and indirect effects of each independent variable on the dependent one....

  14. Naturally Occurring Animal Models with Outer Retina Phenotypes

    OpenAIRE

    Baehr, Wolfgang; Frederick, Jeanne M.

    2009-01-01

    Naturally occurring and laboratory generated animal models serve as powerful tools with which to investigate the etiology of human retinal degenerations, especially retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and macular degeneration (MD). Much progress has been made in elucidating gene defects underlying disease, in understanding mechanisms leading to disease, and in designing molecules for translational research and gene-based therapy to interfere with...

  15. Animal Models of Early Life Stress: Implications for Understanding Resilience

    OpenAIRE

    Lyons, David M.; Parker, Karen J.; Schatzberg, Alan F.

    2010-01-01

    In the mid-1950s, Levine and his colleagues reported that brief intermittent exposure to early life stress diminished indications of subsequent emotionality in rats. Here we review ongoing studies of a similar process in squirrel monkeys. Results from these animal models suggest that brief intermittent exposure to stress promotes the development of arousal regulation and resilience. Implications for programs designed to enhance resilience in human development are discussed.

  16. The role of animal models in tendon research

    OpenAIRE

    Hast, M. W.; Zuskov, A.; Soslowsky, L. J.

    2014-01-01

    Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the stru...

  17. ANIMAL MODELS FOR HUNTINGTON’S DISEASES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Sharma Manisha

    2012-10-01

    Full Text Available Huntington's disease (HD is an inherited autosomal, progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea, cognitive impairments and psychiatric disturbances. HD is caused by an abnormal expansion of a CAG region located in exon 1 of the gene encoding the huntingtin protein (Htt and is the causative factor in the pathogenesis of HD Animal models of HD have provided insight into disease pathology and the outcomes of thera- peutic strategies. Earlier studies of HD most often used toxin-induced models to study mitochondrial impairment and excitotoxicity-induced cell death, which are both mechanisms of degeneration seen in the HD brain. These models, based on 3-nitropropionic acid and quinolinic acid, respectively, are still often used in HD studies. The discovery in 1993 of the huntingtin mutation led to the creation of newer models that incorporate a similar genetic defect. These models, which include transgenic and knock-in rodents, are more representative of the HD progression and pathology. An even more recent model that uses a ovine transgenic model (sheep model,fly models ,cell cultures models for better understanding of gene mutation in and in mammalian and nonhuman primates, as it is difficult to produce genetic models in these species. This article examines the aforementioned models and describes their use in HD research, including aspects of the creation, de- livery, pathology, and tested therapies for each model.

  18. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

    Directory of Open Access Journals (Sweden)

    Raul Torres-Ruiz

    2015-09-01

    Full Text Available The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers.

  19. Animal models of bipolar mania: The past, present and future.

    Science.gov (United States)

    Logan, R W; McClung, C A

    2016-05-01

    Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly six million (∼2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying 'mood' cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD. PMID:26314632

  20. 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.