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Sample records for diabetes animal model

  1. Animal models of obesity and diabetes mellitus

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

    2018-01-01

    More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

  2. Phenotyping animal models of diabetic neuropathy

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

    2014-01-01

    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......NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...

  3. Animal Models of Diabetes Mellitus for Islet Transplantation

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    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.

  4. Animal Models of Diabetic Retinopathy: Summary and Comparison

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    Lo, Amy C. Y.

    2013-01-01

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

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

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

    2016-01-01

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

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

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

    2015-06-01

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

  7. Animal models for clinical and gestational diabetes: maternal and fetal outcomes

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    Kiss Ana CI

    2009-10-01

    Full Text Available Abstract Background Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl and mild diabetes (glycemia between 120 and 300 mg/dl on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. Methods On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16, severe (n = 50 and mild diabetes (n = 30. At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Results Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Conclusion Experimental models of severe diabetes during pregnancy

  8. Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

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    Suvi E. Heinonen

    2015-01-01

    Full Text Available Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease and microvascular disorders leading to damage of the kidneys (nephropathy and eyes (retinopathy. Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative, the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.

  9. Advancements and challenges in generating accurate animal models of gestational diabetes mellitus

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    Pasek, Raymond C.

    2013-01-01

    The maintenance of glucose homeostasis during pregnancy is critical to the health and well-being of both the mother and the developing fetus. Strikingly, approximately 7% of human pregnancies are characterized by insufficient insulin production or signaling, resulting in gestational diabetes mellitus (GDM). In addition to the acute health concerns of hyperglycemia, women diagnosed with GDM during pregnancy have an increased incidence of complications during pregnancy as well as an increased risk of developing type 2 diabetes (T2D) later in life. Furthermore, children born to mothers diagnosed with GDM have increased incidence of perinatal complications, including hypoglycemia, respiratory distress syndrome, and macrosomia, as well as an increased risk of being obese or developing T2D as adults. No single environmental or genetic factor is solely responsible for the disease; instead, a variety of risk factors, including weight, ethnicity, genetics, and family history, contribute to the likelihood of developing GDM, making the generation of animal models that fully recapitulate the disease difficult. Here, we discuss and critique the various animal models that have been generated to better understand the etiology of diabetes during pregnancy and its physiological impacts on both the mother and the fetus. Strategies utilized are diverse in nature and include the use of surgical manipulation, pharmacological treatment, nutritional manipulation, and genetic approaches in a variety of animal models. Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures. PMID:24085033

  10. Lotus leaf alleviates hyperglycemia and dyslipidemia in animal model of diabetes mellitus

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    Kim, Ah-Rong; Jeong, Soo-Mi; Kang, Min-Jung; Jang, Yang-Hee; Choi, Ha-Neul; Kim, Jung-In

    2013-01-01

    The purpose of this study was to investigate the effects of lotus leaf on hyperglycemia and dyslipidemia in animal model of diabetes. Inhibitory activity of ethanol extract of lotus leaf against yeast ?-glucosidase was measured in vitro. The effect of lotus leaf on the postprandial increase in blood glucose levels was assessed in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without lotus leaf extract (500 mg/kg) was administered to the rats after an overnight fast...

  11. [Advances in diabetic animal models and its application in the traditional Chinese medicine research].

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    Cheng, Long; Shen, Zhu-fang; Sun, Gui-bo; Sun, Xiao-bo

    2015-08-01

    The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.

  12. Animal models for assessing the impact of natural products on the aetiology and metabolic pathophysiology of Type 2 diabetes.

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    Asrafuzzaman, Md; Cao, Yingnan; Afroz, Rizwana; Kamato, Danielle; Gray, Susan; Little, Peter J

    2017-05-01

    Type 2 diabetes mellitus is a complex and heterogeneous disorder which in its most common manifestation arises from insulin resistance and later insulin insufficiency. Type 2 diabetes is characterised by impaired insulin sensitivity and diagnosed as hyperglycaemia. Because of its cardiovascular consequences, Type 2 diabetes represents one of the world's leading causes of mortality and morbidity. Drug discovery and development are required to produce better ways to prevent, treat and manage diabetes and its complications. Diabetes is a human, not an animal disease, so animals do not get Type 2 diabetes. However there are animal models which are variously suitable for the investigation of new agents for the treatment of Type 2 diabetes. In this Review we have examined the various models that are available for the study of natural products with a focus on models (genetic, nutritional and spontaneous) for the metabolic abnormities of diabetes. These models are also relevant to the investigation of Western medicines for the treatment of diabetes. A suitable experimental model plays an important role in drug discovery for translational studies leading to increased understanding of the molecular basis and management of diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Diabetes Mellitus Induces Alzheimer’s Disease Pathology: Histopathological Evidence from Animal Models

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    Nobuyuki Kimura

    2016-04-01

    Full Text Available Alzheimer’s disease (AD is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs and neurofibrillary tangles (NFTs in the brain. Although genetic studies show that β-amyloid protein (Aβ, the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology.

  14. Animal models

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    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...

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

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

    2016-01-25

    Streptozotocin (STZ) has been extensively used over the last three decades to induce diabetes in various animal species and to help screen for hypoglycemic drugs. STZ induces clinical features in animals that resemble those associated with diabetes in humans. For this reason STZ treated animals have been used to study diabetogenic mechanisms and for preclinical evaluation of novel antidiabetic therapies. However, the physiochemical characteristics and associated toxicities of STZ are still major obstacles for researchers using STZ treated animals to investigate diabetes. Another major challenges in STZ-induced diabetes are sustaining uniformity, suitability, reproducibility and induction of diabetes with minimal animal lethality. Lack of appropriate use of STZ was found to be associated with increased mortality and animal suffering. During STZ use in animals, attention should be paid to several factors such as method of preparation of STZ, stability, suitable dose, route of administration, diet regimen, animal species with respect to age, body weight, gender and the target blood glucose level used to represent hyperglycemia. Therefore, protocol for STZ-induced diabetes in experimental animals must be meticulously planned. This review highlights specific skills and strategies involved in the execution of STZ-induced diabetes model. The present review aims to provide insight into diabetogenic mechanisms of STZ, specific toxicity of STZ with its significance and factors responsible for variations in diabetogenic effects of STZ. Further this review also addresses ways to minimize STZ-induced mortality, suggests methods to improve STZ-based experimental models and best utilize them for experimental studies purported to understand diabetes pathogenesis and preclinical evaluation of drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Antidiabetic Effect of Salvianolic Acid A on Diabetic Animal Models via AMPK Activation and Mitochondrial Regulation

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    Guifen Qiang

    2015-05-01

    Full Text Available Background/Aims: Diabetes mellitus (DM characterized by hyperglycemia contributes to macrovascular and microvascular complications. Salvianolic acid A (SalA is a polyphenolic compound isolated from the root of Salvia miltiorrhiza Bunge, which is a traditional Chinese medicine widely used to treat cardiovascular diseases. However, little is known about its antidiabetic effect. Our study aimed to investigate the in vivo and in vitro antidiabetic effect of SalA and the underlying mechanisms. Methods: Alloxan-induced type 1 diabetic mice and high-fat diet (HFD and low-dose streptozotocin (STZ-induced type 2 diabetic rats received SalA treatment. Blood glucose, oral glucose tolerance test (OGTT, 24-h food and water intake were monitored. In vitro, glucose consumption and uptake were measured in HepG2 cells and L6 myotubes. Mitochondrial function was detected in hepatic and skeletal muscle mitochondria. AMP-activated protein kinase (AMPK and Akt were analyzed by western blot. Results: In both type 1 and type 2 diabetic animals, SalA lowered fasting blood glucose (FBG and fed blood glucose in dose-dependent manner, as well as reduced 24-h food and water intake. In vitro, SalA caused dose-dependent increase in glucose consumption and enhanced glucose uptake. SalA significantly increased ATP production from 10 min to 12 h in HepG2 cells and L6 myotubes. Interestingly, SalA decreased mitochondrial membrane potential (MMP in HepG2 cells. Furthermore, SalA improved hepatic and skeletal muscle mitochondrial function, increased ATP production, and concurrently decreased MMP. In particularly, SalA activated AMPK phosphorylation through Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ/AMPK signaling pathway, independent of liver kinase 1 (LKB1/AMPK pathway. However, SalA didn't show any effect on insulin secretagogue and activation of PI3K/Akt signaling pathway. Conclusion: SalA exhibits the antidiabetic effects in diabetic animal models through

  17. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

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    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

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

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    Bernal, Antonio; Mahía, Javier; Puerto, Amadeo

    2016-07-01

    The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The effect of hyperglycaemia on osseointegration: a review of animal models of diabetes mellitus and titanium implant placement.

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    King, Shalinie; Klineberg, Iven; Levinger, Itamar; Brennan-Speranza, Tara C

    2016-12-01

    Patients with type 2 diabetes mellitus have a higher risk of dental and/or orthopaedic implant failure. However, the mechanism behind this phenomenon is unclear, and animal studies may prove useful in shedding light on the processes involved. This review considers the available literature on rat models of diabetes and titanium implantation. The process of osseointegration whereby direct contact is achieved between bone and an implant surface depends on healthy bone metabolism. Collective evidence suggests that hyperglycaemia adversely affects bone turnover and the quality of the organic matrix resulting in an overall deterioration in the quality, resilience and structure of the bone tissue. This in turn results in compromised osseointegration in patients receiving dental and orthopaedic implants. The incidence of diabetes mellitus (DM), which is a chronic metabolic disorder resulting in hyperglycaemia, is rising. Of particular significance is the rising incidence of adult onset type 2 diabetes mellitus (T2DM) in an ageing population. Understanding the effects of hyperglycaemia on osseointegration will enable clinicians to manage health outcomes for patients receiving implants. Much of our understanding of how hyperglycaemia affects osseointegration comes from animal studies. In this review, we critically analyse the current animal studies. Our review has found that most studies used a type 1 diabetes mellitus (T1DM) rodent model and looked at a young male population of rodents. The pathophysiology of T1DM is however very different to that of T2DM and is not representative of T2DM, the incidence of which is rising in the ageing adult population. Genetically modified rats have been used to model T2DM, but none of these studies have included female rats and the metabolic changes in bone for some of these models used are not adequately characterized. Therefore, the review suggests that the study population needs to be broadened to include both T1DM and T2DM models

  20. Animal models of disease: classification and etiology of diabetes in dogs and cats

    OpenAIRE

    Nelson, R W; Reusch, C E

    2014-01-01

    Diabetes mellitus is a common disease in dogs and cats. The most common form of diabetes in dogs resembles type 1 diabetes in humans. Studies suggest that genetics, an immune-mediated component, and environmental factors are involved in the development of diabetes in dogs. A variant of gestational diabetes also occurs in dogs. The most common form of diabetes in cats resembles type 2 diabetes in humans. A major risk factor in cats is obesity. Obese cats have altered expression of several insu...

  1. Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models

    DEFF Research Database (Denmark)

    Claesson, M H; Nicoletti, F; Stosic-Grujicic, S

    2008-01-01

    Type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD) are multifactorial disorders of autoimmune origin.Several microbial agents have been reported to be associated with the development of type 1 diabetes and inflammatory bowel diseases in animal models by different mechanisms...

  2. Animal models of disease: classification and etiology of diabetes in dogs and cats.

    Science.gov (United States)

    Nelson, Richard W; Reusch, Claudia E

    2014-09-01

    Diabetes mellitus is a common disease in dogs and cats. The most common form of diabetes in dogs resembles type 1 diabetes in humans. Studies suggest that genetics, an immune-mediated component, and environmental factors are involved in the development of diabetes in dogs. A variant of gestational diabetes also occurs in dogs. The most common form of diabetes in cats resembles type 2 diabetes in humans. A major risk factor in cats is obesity. Obese cats have altered expression of several insulin signaling genes and glucose transporters and are leptin resistant. Cats also form amyloid deposits within the islets of the pancreas and develop glucotoxicity when exposed to prolonged hyperglycemia. This review will briefly summarize our current knowledge about the etiology of diabetes in dogs and cats and illustrate the similarities among dogs, cats, and humans. © 2014 Society for Endocrinology.

  3. Oral insulin delivery by self-assembled chitosan nanoparticles: In vitro and in vivo studies in diabetic animal model

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    Mukhopadhyay, Piyasi; Sarkar, Kishor [Department of Polymer Science and Technology, 92, A.P.C. Road, Kolkata-700009, University of Calcutta (India); Chakraborty, Mousumi; Bhattacharya, Sourav; Mishra, Roshnara [Department of Physiology, 92, A.P.C. Road, Kolkata-700009, University of Calcutta (India); Kundu, P.P., E-mail: ppk923@yahoo.com [Department of Polymer Science and Technology, 92, A.P.C. Road, Kolkata-700009, University of Calcutta (India)

    2013-01-01

    We have developed self-assembled chitosan/insulin nanoparticles for successful oral insulin delivery. The main purpose of our study is to prepare chitosan/insulin nanoparticles by self-assembly method, to characterize them and to evaluate their efficiency in vivo diabetic model. The size and morphology of the nanoparticles were analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The average particle size ranged from 200 to 550 nm, with almost spherical or sub spherical shape. An average insulin encapsulation within the nanoparticles was {approx} 85%. In vitro release study showed that the nanoparticles were also efficient in retaining good amount of insulin in simulated gastric condition, while significant amount of insulin release was noticed in simulated intestinal condition. The oral administrations of chitosan/insulin nanoparticles were effective in lowering the blood glucose level of alloxan-induced diabetic mice. Thus, self-assembled chitosan/insulin nanoparticles show promising effects as potential insulin carrier system in animal models. Highlights: Black-Right-Pointing-Pointer Self-assembled chitosan/insulin nanoparticle preparation. Black-Right-Pointing-Pointer Almost spherical or sub-spherical nanoparticles observed under microscope. Black-Right-Pointing-Pointer Good insulin encapsulation of the nanoparticles. Black-Right-Pointing-Pointer Nanoparticles reduced blood glucose level significantly in diabetic mice.

  4. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals

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    Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard

    2015-01-01

    From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis...

  5. Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

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    Samira Tajbakhsh

    2015-01-01

    Full Text Available Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1 has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS, suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1 per se are not sufficient to prematurely shorten vascular telomeres.

  6. Liraglutide, but not vildagliptin, restores normoglycaemia and insulin content in the animal model of type 2 diabetes, Psammomys obesus

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    Vedtofte, Louise; Bodvarsdottir, Thóra B; Gotfredsen, Carsten F

    2010-01-01

    group of animals was kept on low-energy diet and seven groups were given high-energy diet (HED) that induced diabetes over a four week period. Non-fasting morning blood glucose, body weight, HbA(1C) and pancreatic insulin content were measured and beta cell mass (BCM), proliferation and apoptosis......In order to investigate the effect and mechanism of liraglutide and vildagliptin in diabetic Psammomys obesus, we examined proliferation and apoptosis of beta-cells, beta-cell mass (BCM), and pancreatic insulin content after zero, six and fourteen days of treatment compared to control groups. One...

  7. Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

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    Machado Ubiratan F

    2011-04-01

    Full Text Available Abstract Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2 in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP and heart rate variability (spectral analysis one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting. Results Higher glycemia (p vs. nondiabetics (p vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

  8. Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

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    Hyun Cheol Jeong

    2017-12-01

    Full Text Available Purpose: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT have been investigated as treatments for refractory erectile dysfunction (ED, but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. Materials and Methods: Diabetes mellitus (DM-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. Results: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01. As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05. Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson’s trichrome staining (p<0.05. Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS expression levels were restored to levels in the DM group (p<0.05. Conclusions: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

  9. Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Haruka Amitani

    Full Text Available Hydrogen (H(2 acts as a therapeutic antioxidant. However, there are few reports on H(2 function in other capacities in diabetes mellitus (DM. Therefore, in this study, we investigated the role of H(2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2 promoted 2-[(14C]-deoxy-d-glucose (2-DG uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K, protein kinase C (PKC, and AMP-activated protein kinase (AMPK, although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p. and oral (p.o. administration. However, long-term p.o. administration of H(2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

  10. Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model

    Directory of Open Access Journals (Sweden)

    Muhammad AA

    2016-05-01

    Full Text Available Abubakar Amali Muhammad,1 Palanisamy Arulselvan,1 Cheah Pike See,2 Farida Abas,3 Sharida Fakurazi1,2 1Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, 2Unit of Anatomy, Department of Human Anatomy, Faculty of Medicine and Health Sciences, 3Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15% of diabetics and up to 15%–24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine. Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue

  11. Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes

    DEFF Research Database (Denmark)

    Haupt-Jørgensen, Martin; Buschard, Karsten; Hansen, Axel Kornerup

    2016-01-01

    Background Gluten-free (GF) diet alleviates type 1 diabetes in animal models and possibly in humans. We recently showed that fatty acid-induced insulin secretion is enhanced by enzymatically digested gluten (gliadin) stimulation in INS-1E insulinoma cells. We therefore hypothesized that GF diet...... would induce beta-cell rest and ameliorate type 2 diabetes. Methods C57BL/6JBomTac (B6) mice were fed a high-fat (HF), gluten-free high-fat (GF–HF), standard (STD) or gluten-free (GF) diet for 42 weeks. Results Short-term (6–24 weeks) GF–HF versus HF feeding impaired glucose tolerance and increased...... capacity controls pancreas volume. Thus, long-term GF diets may be beneficial for obese type 2 diabetes patients and trials should be performed....

  12. A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes.

    Science.gov (United States)

    Mathavan, Sangeetha; Chen-Tan, Nigel; Arfuso, Frank; Al-Salami, Hani

    2016-10-01

    Gliclazide (G) is a commonly prescribed drug for Type 2 diabetes (T2D). In a recent study, we found that when G was combined with a primary bile acid, and gavaged to an animal model of Type 1 diabetes (T1D), it exerted a hypoglycemic effect. We hypothesized this to be due to metabolic activation of the primary bile acid into a secondary or a tertiary bile acid, which enhanced G solubility and absorption. The tertiary bile acid, taurocholic acid (TCA), has shown strong permeation-enhancing effects in vivo. Thus, we aimed to design, characterize, and test microcapsules incorporating G and TCA in an animal model of T1D. Microcapsules were prepared using the polymer sodium alginate (SA). G-SA microcapsules (control) and G-TCA-SA microcapsules (test) were extensively examined (in-vitro) at different pH and temperatures. The microcapsules were gavaged to diabetic rats, and blood glucose and G concentrations in serum were examined. Ex-vivo studies were also performed using a muscle cell line (C2C12), and cell viability and glucose intake post-treatment were examined. G-TCA-SA microcapsules showed good stability, uniformity, and thermal and chemical excipient compatibilities. TCA did not change the size or the shape of the microcapsules, but it enhanced their mechanical resistance and reduced their swelling properties. G-TCA-SA enhanced the viability of C2C12 cells over 24 hours, and exerted a hypoglycemic effect in alloxan-induced type-1 diabetic rats. The incorporation of TCA into G-microcapsules resulted in functionally improved microcapsules with a positive effect on cell viability and glycemic control in Type-1 diabetic animals.

  13. The association effect of insulin and clonazepam on oxidative stress in liver of an experimental animal model of diabetes and depression.

    Science.gov (United States)

    Wayhs, Carlos Alberto Yasin; Tortato, Caroline; Mescka, Caroline Paula; Pasquali, Matheus Augusto; Schnorr, Carlos Eduardo; Nin, Maurício Schüler; Barros, Helena Maria Tannhauser; Moreira, José Claudio Fonseca; Vargas, Carmen Regla

    2013-05-01

    It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model. This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST). Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60 mg/kg in male Wistar rats. Insulin (4 IU/kg) plus CNZ acute i.p. treatment (0.25 mg/kg) was administered 24, 5 and 1 h before the FST. Nondiabetic control rats received i.p. injections of saline (1 mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined. Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04 ± 0.55), while the activity of catalase (51.83 ± 19.02) and SOD (2.30 ± 1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15 ± 0.02) in the liver of the animals was decreased. Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST.

  14. Establishing a Large-Animal Model for In Vivo Reprogramming of Bile Duct Cells into Insulin-Secreting Cells to Treat Diabetes.

    Science.gov (United States)

    Hill, Caitlin M; Banga, Anannya; Abrahante, Juan E; Yuan, Ce; Mutch, Lucas A; Janecek, Jody; O'Brien, Timothy; Graham, Melanie L; Dutton, James R

    2017-06-01

    Type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. Islet transplantation, while highly effective, is severely limited by shortage of donor organs. Clinical translation of beta cells derived from pluripotent stem cells is also not yet a reality, and alternative approaches to solving the replacement of lost beta cell function are required. In vivo direct reprogramming offers an attractive approach to generating new endogenous insulin-secreting cells by permanently altering the phenotype of somatic cells after transient expression of transcription factors. Previously, we have successfully restored control of blood glucose in diabetic mice by reprogramming liver cells into glucose-sensitive insulin-secreting cells after the transient, simultaneous delivery of three transcription factors (Pdx1, Ngn3, and MafA) to the liver of diabetic mice, using an adenoviral vector (Ad-PNM). Establishing a clinically relevant, large-animal model is a critical next step in translating this approach beyond the proof-of-principle stage in rodents and allowing investigation of vector design, dose and delivery, host response to vector infusion, and establishment of suitable criteria for measuring safety and efficacy. In this feasibility study we infused Ad-PNM into the liver of three diabetic cynomolgus macaques via portal vein catheter. Vector presence and cargo gene and protein expression were detected in liver tissue after infusion with no adverse effects. Refinement of immune suppression significantly extended the period of exogenous PNM expression. This pilot study establishes the

  15. Role of Momordica Charantia L. as Herbal Medicine to Cure Hyperglycemia In Vitro on Induced Diabetic Model Animals

    International Nuclear Information System (INIS)

    Mushtaq, W.; Ishtiaq, M.; Hussain, T.; Tariq, M.; Asghar, R.

    2016-01-01

    The present study was aimed to explore antidiabetic potential of wild fruit of Momordica charantia L. (Family: Cucurbitaceae) from local germplasm of District Bhimber Communities, Azad Kashmir. The purpose was to evaluate the herbal recipe of food folklores of the remote rural area, where majority population relies on herbal therapeutics. Ethnomedicinal knowledge was collected through Rapid Appraisal Approach (RAA) along with structured and semi-structured interviews with local people and herbalist. Pharmacological analysis was conducted in the laboratory using Rabbits as model organisms, diabetics were induced by use of alloxan. The antihyperglycemic effect of ethanol extract at 1mg/kg and 3mg/kg is studied in normal, glucose loaded hyperglycemic and alloxan induced Type2 diabetic rats by oral dose administration for 7, 15 and 30 days. The blood glucose level of normal control and treatment groups were monitored by using Star glucometer. This research explored that considerable reduction in sugar level was observed on 7th and 15th days samplings in both treatments (T/sub 1-group/ with 1g dose has 224+-12 value and T/sub 2-group/ with 3g dose has 149+-1.4 value) in comparison with control group which showed 542+-6 glucose reading. The body weights was increased by 4.4 percent in normal control group, in diabetic control group decreased by 1.35 percent, in T/sub 1-group/ decreases by 19 percent and in T/sub 2-group/ by decrease 37 percent. Serum insulin level was also improved in both treatment groups but comparatively in T/sub 2-group/, its improvement was more. The study demonstrated that ethanolic extract of Momordica charantiaL has potential antidiabetic property in Type2 diabetes mellitus, thus justifying the traditional usage of plant as food medicine. (author)

  16. Modelling Farm Animal Welfare

    Science.gov (United States)

    Collins, Lisa M.; Part, Chérie E.

    2013-01-01

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

  17. Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet.

    Science.gov (United States)

    Han, Nayoung; Chae, Jung-Woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-Moon; Song, Byungjeong; Kwon, Kwang-Il; Kim, Sang Kyum; Yun, Hwi-Yeol

    2018-01-01

    Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model. The model building and simulation were performed using NONMEM® (ver. 7.3.0) assisted by Perl-Speaks-NONMEM (PsN, ver. 4.3.0). Model parameters were derived using first-order conditional estimation method with interactions permitted among the parameters (FOCE-INTER). NCA was conducted using Phoenix (ver. 6.4.0). For all tests, we considered a P -value < 0.05 to reflect statistical significance. Our model featured seven compartments that considered all parts of the cycle by applying non-linear mixed effects model. Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the metabolism of homocysteine was reduced under diabetic conditions, and consequently homocysteine accumulated in the elimination phase.Using our model, we performed simulations to compare the changes in plasma methionine and homocysteine concentrations between ZDF and normal rats, by multiple administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. The levels of methionine and homocysteine were elevated approximately two- and three-fold, respectively, in ZDF rats, while there were no changes observed in the normal control rats. These results can be interpreted to mean that both methionine and homocysteine will accumulate in patients with T2DM, who regularly consume high-methionine foods.

  18. 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 ...

  19. 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...

  20. Animal models in fetal medicine and obstetrics

    DEFF Research Database (Denmark)

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

    2017-01-01

    Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and vary regarding...... the animal characteristics (size, number of fetuses, placenta barrier type, etc). While none of these exactly mirrors the human condition, different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep and pigs) are here described with respect to advantages and limitations...

  1. 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

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

    International Nuclear Information System (INIS)

    Seo, Daniele

    2017-01-01

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

  3. Animal models of sarcoidosis.

    Science.gov (United States)

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

    2017-03-01

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

  4. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals.

    Science.gov (United States)

    Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard; Pedersen, Henrik Duelund; Martinussen, Torben; Kildegaard, Jonas; Heegaard, Peter M H; Lykkesfeldt, Jens; Olsen, Lisbeth Høier

    2015-09-22

    From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis in human patients, inclusion of this disease aspect in the characterization of a such model, is highly relevant. The objective of this study was to evaluate the effect of mild streptozotocin-induced diabetes on ex- and in vivo end-points in a diet-induced atherosclerotic minipig model. Castrated male Göttingen minipigs were fed standard chow (CD), atherogenic diet alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D). Circulating markers of inflammation (C-reactive protein (CRP), oxidized low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and glucose metabolism were evaluated together with coronary and aortic atherosclerosis after 22 or 43 diet-weeks. Group differences were evaluated by analysis of variance for parametric data and Kruskal-Wallis test for non-parametric data. For qualitative assessments, Fisher's exact test was applied. For all analyses, p diabetes was observed on plaque area, lesion severity or inflammatory markers.

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

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

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

  6. Animal Models of Glaucoma

    Directory of Open Access Journals (Sweden)

    Rachida A. Bouhenni

    2012-01-01

    Full Text Available Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.

  7. DNA Advanced Glycation End Products (DNA-AGEs) Are Elevated in Urine and Tissue in an Animal Model of Type 2 Diabetes.

    Science.gov (United States)

    Jaramillo, Richard; Shuck, Sarah C; Chan, Yin S; Liu, Xueli; Bates, Steven E; Lim, Punnajit P; Tamae, Daniel; Lacoste, Sandrine; O'Connor, Timothy R; Termini, John

    2017-02-20

    More precise identification and treatment monitoring of prediabetic/diabetic individuals will require additional biomarkers to complement existing diagnostic tests. Candidates include hyperglycemia-induced adducts such as advanced glycation end products (AGEs) of proteins, lipids, and DNA. The potential for DNA-AGEs as diabetic biomarkers was examined in a longitudinal study using the Lepr db/db animal model of metabolic syndrome. The DNA-AGE, N 2 -(1-carboxyethyl)-2'-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from the urine and tissue of hyperglycemic and normoglycemic mice. Hyperglycemic mice (fasting plasma glucose, FPG, ≥ 200 mg/dL) displayed a higher median urinary CEdG value (238.4 ± 112.8 pmol/24 h) than normoglycemic mice (16.1 ± 11.8 pmol/24 h). Logistic regression analysis revealed urinary CEdG to be an independent predictor of hyperglycemia. Urinary CEdG was positively correlated with FPG in hyperglycemic animals and with HbA1c for all mice. Average tissue-derived CEdG was also higher in hyperglycemic mice (18.4 CEdG/10 6 dG) than normoglycemic mice (4.4 CEdG/10 6 dG). Urinary CEdG was significantly elevated in Lepr db/db mice relative to Lepr wt/wt , and tissue CEdG values increased in the order Lepr wt/wt < Lepr wt/db < Lepr db/db . These data suggest that urinary CEdG measurement may provide a noninvasive quantitative index of glycemic status and augment existing biomarkers for the diagnosis and monitoring of diabetes.

  8. ANIMAL MODELS IN SURGICAL

    African Journals Online (AJOL)

    ASSEMBLED BY

    1 Dept.of Veterinary Surgery and Medicine 2Veterinary Teaching Hospital Ahmadu Bello University. Zaria .... unnecessary suffering., Administration of poisons .... way that humans are. Vivisection/ Surgical Training And Research. Animal model use: In both the human and veterinary medical practice, there continue to be ...

  9. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals

    DEFF Research Database (Denmark)

    Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard

    2015-01-01

    From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis...... Göttingen minipigs were fed standard chow (CD), atherogenic diet alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D). Circulating markers of inflammation (C-reactive protein (CRP), oxidized low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and glucose...... metabolism were evaluated together with coronary and aortic atherosclerosis after 22 or 43 diet-weeks. Group differences were evaluated by analysis of variance for parametric data and Kruskal-Wallis test for non-parametric data. For qualitative assessments, Fisher's exact test was applied. For all analyses...

  10. Animal models of sepsis.

    Science.gov (United States)

    Fink, Mitchell P

    2014-01-01

    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, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

  11. Anti-hepatotoxic activities of Hibiscus sabdariffa L. in animal model of streptozotocin diabetes-induced liver damage.

    Science.gov (United States)

    Adeyemi, David O; Ukwenya, Victor O; Obuotor, Efere M; Adewole, Stephen O

    2014-07-30

    Flavonoid-rich aqueous fraction of methanolic extract of Hibiscus sabdariffa calyx was evaluated for its anti-hepatotoxic activities in streptozotocin-induced diabetic Wistar rats. Diabetes Mellitus was induced in Wistar rats by a single i.p injection of 80 mg/kg b.w. streptozotocin (STZ) dissolved in 0.1 M citrate buffer (pH 6.3). The ameliorative effects of the extract on STZ-diabetes induced liver damage was evident from the histopathological analysis and the biochemical parameters evaluated in the serum and liver homogenates. Reduced levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (3.76 ± 0.38 μM, 0.42 ± 0.04 U/L, 41.08 ± 3.04 U/ml, 0.82 ± 0.04 U/L respectively) in the liver of diabetic rats were restored to a near normal level in the Hibiscus sabdariffa-treated rats (6.87 ± 0.51 μM, 0.72 ± 0.06 U/L, 87.92 ± 5.26 U/ml, 1.37 ± 0.06 U/L respectively). Elevated levels of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) in the serum of diabetic rats were also restored in Hibiscus sabdariffa -treated rats. Examination of stained liver sections revealed hepatic fibrosis and excessive glycogen deposition in the diabetic rats. These pathological changes were ameliorated in the extract-treated rats. The anti-hepatotoxic activity of Hibiscus sabdariffa extract in STZ diabetic rats could be partly related to its antioxidant activity and the presence of flavonnoids.

  12. Animal Models of Atherosclerosis

    Science.gov (United States)

    Getz, Godfrey S.; Reardon, Catherine A.

    2012-01-01

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

  13. Animal models of spondyloarthritis.

    Science.gov (United States)

    Lories, Rik J U

    2006-07-01

    The aim of this article is to review new insights into spondyloarthritis obtained in animal models during the last year. HLA-B27 misfolding has been demonstrated in HLA-B27/human beta2-microglobulin transgenic rats. HLA-B27 misfolding is associated with a typical unfolded protein stress response and with an interferon-response signature. Prebiotic treatment of these rats reduced colitis and arthritis. Proteoglycan-induced spondylitis is distinct from proteoglycan-induced arthritis. Specific susceptibility loci for proteoglycan-induced spondylitis have been demonstrated. Bone morphogenetic proteins are important in new cartilage and bone formation in ankylosing enthesitis. Psoriasis and psoriatic arthritis-like disease develops in conditional double JunB/c-Jun knockout mice. Insights into the molecular signaling pathways driving HLA-B27 associated spondylitis, autoimmune spondylitis, ankylosing enthesitis and psoriasis, resulting from animal models, identify new and specific therapeutic targets in spondyloarthritis.

  14. 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, ...

  15. Animal Models of Hemophilia

    Science.gov (United States)

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

    2013-01-01

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

  16. Animal models of schizophrenia

    Science.gov (United States)

    Jones, CA; Watson, DJG; Fone, KCF

    2011-01-01

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

  17. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress in Rats

    Directory of Open Access Journals (Sweden)

    Siti Hajar Abdul Aziz

    2016-01-01

    Full Text Available This study attempts to develop an experimental gestational diabetes mellitus (GDM animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0. Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin, lipid profiles (total cholesterol, triglycerides, HDL, and LDL, genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1, glucose transporters (GLUT-2 and GLUT-4, proinflammatory cytokines (IL-6, TNF-α, and antioxidants (SOD, CAT, and GPX on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations.

  18. Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes.

    Science.gov (United States)

    Haupt-Jorgensen, Martin; Buschard, Karsten; Hansen, Axel K; Josefsen, Knud; Antvorskov, Julie Christine

    2016-10-01

    Gluten-free (GF) diet alleviates type 1 diabetes in animal models and possibly in humans. We recently showed that fatty acid-induced insulin secretion is enhanced by enzymatically digested gluten (gliadin) stimulation in INS-1E insulinoma cells. We therefore hypothesized that GF diet would induce beta-cell rest and ameliorate type 2 diabetes. C57BL/6JBomTac (B6) mice were fed a high-fat (HF), gluten-free high-fat (GF-HF), standard (STD) or gluten-free (GF) diet for 42 weeks. Short-term (6-24 weeks) GF-HF versus HF feeding impaired glucose tolerance and increased fasting glucose. Long-term (36-42 weeks) GF-HF versus HF feeding improved glucose tolerance and decreased fasting leptin. Mice fed a GF-HF versus HF diet for 42 weeks showed higher volumes of beta cells, islets and pancreas. The beta-cell volume correlated with the islet- and pancreas volume as well as body weight. GF-HF versus HF diet did not influence toll-like receptor 4 (Tlr4), interleukin 1 (IL-1), interleukin 6 (IL-6) or tumour necrosis factor-alpha (TNF-alpha) mRNA expression in intestine. STD versus GF feeding did not affect any parameter studied. Long-term feeding with GF-HF versus HF increases beta-cell volume and improves glucose tolerance in B6 mice. The mechanism may include beta-cell rest, but is unlikely to include TLR4 and proinflammatory cytokines in the intestine. Beta-cell volume correlates with pancreas volume and body weight, indicating that insulin secretion capacity controls pancreas volume. Thus, long-term GF diets may be beneficial for obese type 2 diabetes patients and trials should be performed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet

    OpenAIRE

    Han, Nayoung; Chae, Jung-woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-moon; Song, Byungjeong; Kwon, Kwang-il; Kim, Sang Kyum; Yun, Hwi-yeol

    2018-01-01

    Background Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fat...

  20. Type 2 diabetes models

    DEFF Research Database (Denmark)

    Gram, Dorte Xenia

    2012-01-01

    This chapter deals with type 2 diabetes in vivo models and techniques suitable for testing new anti-diabetic compounds. In particular, the testing of TRP antagonist for beneficial effects against type 2 diabetes is considered. There are many choices of both in vitro techniques and in vivo models......, impaired glucose tolerance, impaired insulin secretion, and insulin resistance in vivo and should, thus, be sufficient to demonstrate preclinical proof of concept of a TRP antagonist in type 2 diabetes in rodents. The experiments are suggestions and could be replaced or supplemented by others....

  1. Antidiabetic dietary materials and animal models.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2016-07-01

    The ever-increasing occurrence of diabetes worldwide demands cost-effective anti-diabetic strategies. Food-based materials have great potential as efficient anti-diabetic agents. Focusing on the literatures of the recent 5years, this review summarizes the methods, findings, and limitations of each research involving non-medicinal foods (individual and mixed) and diabetic animal models. Various types of fruits, vegetables, legumes, cereals, spices, beverages, oilseeds, and edible oils showed antidiabetic effects in different animal models. Animal feeding trials rarely had identical designs in food doses, feeding schedules, and routes of administration, as well as biochemical markers for antidiabetic evaluation. Various possible cellular and metabolic targets were speculated for the anti-hyperglycemic effects of the dietary materials, and the molecular mechanisms of action remain to be better explored. Short-term (maximum 16weeks) antidiabetic studies have been established. Limited safety/tolerability data are available for antidiabetic dietary materials. Findings from current animal studies present a generic antidiabetic dietary pattern associated with plant-based whole foods, which agrees well with the findings of epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. When glucocorticoids change from protective to harmful: Lessons from a type 1 diabetes animal model Cuando los glucocorticoides cambian de protectores a dañinos en un modelo animal de diabetes tipo 1

    Directory of Open Access Journals (Sweden)

    Yanina Revsin

    2009-06-01

    Full Text Available A fundamental question in the neuroendocrinology of stress and adaptation is how stress mediators that are crucial for resilience and health can change into harmful signals enhancing vulnerability to disease. To address this question we focus in the rodent on corticosterone as end product of the hypothalamicpituitary- adrenal (HPA axis, which coordinates the behavioural and physiological response to stressors. The action of corticosterone is mediated by mineralocorticoid (MR and glucocorticoid receptors (GR. The receptors are transcription factors regulating gene transcription but recently these nuclear receptors were found to mediate also rapid non-genomic actions. MR participates in the initial stress reaction important for appraisal and coping processes, while management of the later adaptive phase primarily depends on GR. Imbalance in stress mediators is a characteristic feature of a phenotype vulnerable for stressors. This concept calls for recovery of the MR:GR balance as a therapeutic strategy to promote resilience still present in the diseased brain. As an example, we discuss in this article, how the impact of excessive levels of corticosterone in a pharmacological model of type 1 diabetes can be ameliorated after a brief treatment with a GR antagonist.Una cuestión fundamental en la neuroendocrinología del estrés y la adaptación es saber cómo los mediadores del estrés cruciales para la resiliencia y la salud pueden convertirse en señales dañinas que aumentan la vulnerabilidad a las enfermedades. Para responder a esta pregunta nosotros nos centramos en la corticosterona como producto final del eje hipotálamo-hipófisis-glándula adrenal de los ratones, que coordina las respuestas fisiológicas y conductuales hacia los agentes estresantes. La acción de la corticosterona es mediada por los receptores de los mineralocorticoides (MR y glucocorticoides (GR. Estos receptores son factores nucleares que regulan la transcripción de los

  3. PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals.

    Science.gov (United States)

    Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A

    2016-11-15

    Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. Copyright © 2016. Published by Elsevier B.V.

  4. Animal Models of Neuropsychiatric Disorders

    Science.gov (United States)

    Nestler, Eric J.; Hyman, Steven E.

    2013-01-01

    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, and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported. PMID:20877280

  5. Modelling diabetic nephropathy in mice.

    Science.gov (United States)

    Azushima, Kengo; Gurley, Susan B; Coffman, Thomas M

    2018-01-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN. Questions have been raised, however, about the general utility of mouse models in human drug discovery. Standard mouse models of diabetes typically manifest only modest kidney abnormalities, whereas accelerated models, induced by superimposing genetic stressors, recapitulate key features of human DN. Incorporation of systems biology approaches and emerging data from genomics and metabolomics studies should enable further model refinement. Here, we discuss the current status of mouse models for DN, their limitations and opportunities for improvement. We emphasize that future efforts should focus on generating robust models that reproduce the major clinical and molecular phenotypes of human DN.

  6. 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.

  7. ANIMAL MODELS FOR IMMUNOTOXICITY

    Science.gov (United States)

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

  8. Pig model for diabetes

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a transgenic pig comprising a mutated IAPP gene and displaying a phenotype associated with diabetes. The invention also relates to a transgenic blastocyst, embryo, fetus, donor cell and/or cell nucleusderived from said transgenic pig. The invention further relates...... to use of the transgenic pig as a model system for studying therapy, treatment and/or prevention of diabetes....

  9. Ghrelin mitigates β-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat.

    Science.gov (United States)

    Baena-Nieto, Gloria; Lomas-Romero, Isabel M; Mateos, Rosa M; Leal-Cosme, Noelia; Perez-Arana, Gonzalo; Aguilar-Diosdado, Manuel; Segundo, Carmen; Lechuga-Sancho, Alfonso M

    2017-01-01

    Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the β-cell. Given the immunomodulating effects of ghrelin and its trophic effects on β-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset. BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. β-cell mass, islet area, islet number, β-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test. Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p cell mass loss, enabling the maintenance of β-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations. These findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting β-cell mass. Ghrelin promotes β-cell viability and function through diverse mechanisms that may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Free Radicals Scavenging Capacity, Antidiabetic and Antihypertensive Activities of Flavonoid-Rich Fractions from Leaves of Trichilia emetica and Opilia amentacea in an Animal Model of Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Kiessoun Konaté

    2014-01-01

    Full Text Available Trichilia emetica and Opilia amentacea traditional Burkinabe medicinal plants were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of type 2 diabetes. In vitro and in vivo antioxidant and antihypertensive potential and antilipidemia and antihyperglycemia activities in an animal model of type 2 diabetes mellitus have been studied. The antioxidant activity of the flavonoids from leaves of Trichilia emetica and Opilia amentacea has been evaluated using β-carotene-linoleic acid system, 1,1-diphenyl-2-picrylhydrazyl inhibitory activity, chelation of iron (II ions, and lipid peroxidation which showed more pronounced antioxidant capacities of Trichilia emetica. Total cholesterol concentrations decreased in an animal model of type 2 diabetes mellitus under effects of flavonoid-rich fractions from leaves of Trichilia emetica and Opilia amentacea has been observed. Extract of flavonoid-rich fractions from Trichilia emetica shown maximum radical scavenging activity and possessed marked antiamylase activity which may be due to the presence of certain secondary metabolites. Suggested better antihyperglycemia, antilipidemia, and antihypertensive properties of flavonoid-rich fractions from Trichilia emetica compared to the extract of Opilia amentacea are demonstrating antidiabetic potential of Trichilia emetica as therapeutic targets for the management of type 2 diabetes.

  11. The use of Alloxan and Streptozotocin in Experimental Diabetes Models

    Directory of Open Access Journals (Sweden)

    Zehra Kurçer

    2012-06-01

    Full Text Available Diabetes is a chronic metabolic disease which leads to several acute and chronic complications, morbidity and mortality, and decreased lifespan and quality of life. Therefore, in research studies that aim to enlighten the pathogenesis of diabetes and investigate possible treatment strategies, experimental animal models of diabetes provide many advantages to the investigator. Models of diabetes obtained by chemical induction, diet, surgical manipulations or combination thereof and also new genetically modified animal models are some of the experimental models. Alloxan and streptozotocin (STZ, which are toxic glucose analogues that preferentially accumulate in pancreatic beta cells, are widely used toxic agents to induce experimental diabetes in animals. This review gives an overview on the use of alloxan and STZ to induce chemical diabetes models with reference to their mechanisms, utilizable doses, advantages and disadvantages in diabetes research. Turk Jem 2012; 16: 34-40

  12. MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes.

    Science.gov (United States)

    Kurtz, C Lisa; Peck, Bailey C E; Fannin, Emily E; Beysen, Carine; Miao, Ji; Landstreet, Stuart R; Ding, Shengli; Turaga, Vandana; Lund, P Kay; Turner, Scott; Biddinger, Sudha B; Vickers, Kasey C; Sethupathy, Praveen

    2014-09-01

    MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological factors in complex disease, and promising drug targets. Recent reports suggest that miRNAs are critical regulators of pathways underlying the pathophysiology of type 2 diabetes. In this study, we demonstrate by deep sequencing and real-time quantitative PCR that hepatic levels of Foxa2 mRNA and miR-29 are elevated in a mouse model of diet-induced insulin resistance. We also show that Foxa2 and miR-29 are significantly upregulated in the livers of Zucker diabetic fatty (fa/fa) rats and that the levels of both returned to normal upon treatment with the insulin-sensitizing agent pioglitazone. We present evidence that miR-29 expression in human hepatoma cells is controlled in part by FOXA2, which is known to play a critical role in hepatic energy homeostasis. Moreover, we demonstrate that miR-29 fine-tunes FOXA2-mediated activation of key lipid metabolism genes, including PPARGC1A, HMGCS2, and ABHD5. These results suggest that miR-29 is an important regulatory factor in normal metabolism and may represent a novel therapeutic target in type 2 diabetes and related metabolic syndromes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Animal Models for Candidiasis

    Science.gov (United States)

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

    2014-01-01

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

  14. Animal Models of Bacterial Keratitis

    Science.gov (United States)

    Marquart, Mary E.

    2011-01-01

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

  15. 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

  16. 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. © 2015 Optometry

  17. Animal models of pituitary neoplasia

    OpenAIRE

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

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal mod...

  18. 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...

  19. Animal models of pituitary neoplasia

    Science.gov (United States)

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

    2016-01-01

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

  20. 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.

  1. Small animal models of xenotransplantation.

    Science.gov (United States)

    Wang, Hao

    2012-01-01

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

  2. Animal models for auditory streaming

    Science.gov (United States)

    Itatani, Naoya

    2017-01-01

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

  3. Importância do modelo animal para testar hipóteses sobre a fisiopatologia do binômio diabetes e incontinência urinária feminina = Importance of animal model to test hypotheses about the pathophysiology of the binomial diabetes and female urinary incontinence

    Directory of Open Access Journals (Sweden)

    Marini, Gabriela

    2011-01-01

    Conclusões: o uso de ratas como modelo animal é apropriado para estudos experimentais que testam hipóteses sobre os mecanismos de continência e a fisiopatologia do binômio diabetes mellitus e incontinência urinária, possibilitando assim, soluções de grande valia na prática clínica

  4. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

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

  5. Animal Models of Zika Virus

    Science.gov (United States)

    Bradley, Michael P; Nagamine, Claude M

    2017-01-01

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

  6. XX. Animal models of pneumocystosis

    DEFF Research Database (Denmark)

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

    1998-01-01

    As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent...... 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...

  7. Animal models of drug addiction.

    Science.gov (United States)

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

    2017-09-29

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

  8. Modelling group dynamic animal movement

    DEFF Research Database (Denmark)

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

    2014-01-01

    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......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However......, 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...

  9. Animal Models of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Domenico Santoro

    2014-12-01

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

  10. Animal Models of Periventricular Leukomalacia

    Science.gov (United States)

    Choi, Ehn-Kyoung; Park, Dongsun; Kim, Tae Kyun; Lee, Sun Hee; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Kyung, Jangbeen; Kim, Dajeong; Lee, Woo Ryoung; Suh, Jun-Gyo; Jeong, Eun-Suk; Kim, Seung U.

    2011-01-01

    Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics. PMID:21826166

  11. Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals

    Directory of Open Access Journals (Sweden)

    Wang X

    2014-11-01

    Full Text Available Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA Abstract: Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF rat (fa/fa is an obese animal model frequently used in type 2 diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs, and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline

  12. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation....... An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies...

  13. Wound healing in animal models: review article

    Directory of Open Access Journals (Sweden)

    Fariba Jaffary

    2017-10-01

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

  14. Animal models of RLS phenotypes.

    Science.gov (United States)

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

    2017-03-01

    Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    Directory of Open Access Journals (Sweden)

    Shou-Chieh Wang

    2011-01-01

    Full Text Available Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL and increasing high-density lipoprotein (HDL value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling.

  16. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    Science.gov (United States)

    Wang, Shou-Chieh; Lee, Shiow-Fen; Wang, Chau-Jong; Lee, Chao-Hsin; Lee, Wen-Chin; Lee, Huei-Jane

    2011-01-01

    Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling. PMID:19965962

  17. 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

  18. Animal models and conserved processes.

    Science.gov (United States)

    Greek, Ray; Rice, Mark J

    2012-09-10

    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? 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. 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. We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response

  19. Copeptin: May it be a novel biomarker for insulin theraphy in diabetes? An animal study

    OpenAIRE

    Harman, Ece Harman; Dodurga, Yavuz; Gundogdu, Gulsah; Ayada, Ceylan; Erken, Gulten; Kucukatay, Vural; Avci, Cigir Biray; Genc, Osman

    2014-01-01

    Copeptin is a marker about prognosis of acute illnesses, generally. It may be also an indicator associated with treatment of chronic diseases. We aimed to evaluate copeptin levels in rat models with stress, diabetes, diabetes+insulin. Healthy male Wistar rats, about 3 months old, weighing 200 "250 g, were obtained from University Animal House. They were housed in small cages at standard conditions (24 ± 2°C and 50 ± 5% humidity) with a 12 h light/dark cycle and were fed ad libitum wi...

  20. Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

    Science.gov (United States)

    Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

    2013-01-01

    Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

  1. Parathyroid diseases and animal models.

    Science.gov (United States)

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

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

  2. Parathyroid diseases and animal models

    Directory of Open Access Journals (Sweden)

    Yasuo eImanishi

    2012-06-01

    Full Text Available Circulating calcium and phosphate are tightly regulated by 3 hormones: the active form of vitamin D (1,25-dihydroxyvitamin D, fibroblast growth factor (FGF-23, and parathyroid hormone (PTH. PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

  3. Animal models for cancer cachexia.

    Science.gov (United States)

    Ballarò, Riccardo; Costelli, Paola; Penna, Fabio

    2016-12-01

    Cancer cachexia is a frequent syndrome that affects patient quality of life, anticancer treatment effectiveness, and overall survival. The lack of anticancer cachexia therapies likely relies on the complexity of the syndrome that renders difficult to design appropriate clinical trials and, conversely, on the insufficient knowledge of the underlying pathogenetic mechanisms. The aim of this review is to collect the most relevant latest information regarding cancer cachexia with a special focus on the experimental systems adopted for modeling the disease in translational studies. The scenario of preclinical models for the study of cancer cachexia is not static and is rapidly evolving in parallel with new prospective treatment options. The well established syngeneic models using rodent cancer cells injected ectopically are now used alongside new ones featuring orthotopic injection, human cancer cell or patient-derived xenograft, or spontaneous tumors in genetically engineered mice. The use of more complex animal models that better resemble cancer cachexia, ideally including also the administration of chemotherapy, will expand the understanding of the underlying mechanisms and will allow a more reliable evaluation of prospective drugs for translational purposes.

  4. Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

    Czech Academy of Sciences Publication Activity Database

    Paul, D.S.; Hernández-Zavala, A.; Walton, F.S.; Adair, B.M.; Dědina, Jiří; Matoušek, Tomáš; Stýblo, M.

    2007-01-01

    Roč. 222, č. 3 (2007), s. 305-314 ISSN 0041-008X Grant - others:NIH-FIRCA(US) 1 R03 TW0070507-01 Institutional research plan: CEZ:AV0Z40310501 Source of funding: N - neverejné zdroje Keywords : arsenic * speciation * diabetes Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.846, year: 2007

  5. Development of biomarker specific of pancreatic beta cells (incretin radiolabelled) for image of beta functional mass in diabetic and obese: study in animal model; Desenvolvimento de biomarcador específico de células beta pancreáticas (incretina radiomarcada) para imagem da massa beta funcional em diabéticos e obesos: estudo em modelo animal

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Daniele

    2017-07-01

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

  6. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

    Directory of Open Access Journals (Sweden)

    Mohan Daburkar

    2014-01-01

    Full Text Available Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I, untreated DFUs (Group II, DFUs treated with A. vera gel ethanolic extract (Group III, DFUs treated with topical A. vera gel (Group IV, DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V. The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM. Data were analyzed using one-way analysis of variance (ANOVA after Newman-Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats.

  7. Beneficial Role of Some Natural Products to Attenuate the Diabetic Cardiomyopathy Through Nrf2 Pathway in Cell Culture and Animal Models.

    Science.gov (United States)

    Sathibabu Uddandrao, V V; Brahmanaidu, Parim; Nivedha, P R; Vadivukkarasi, S; Saravanan, Ganapathy

    2017-10-27

    Diabetic cardiomyopathy, as one of the main cardiac complications in diabetic patients, is identified to connect with oxidative stress that is due to interruption in balance between reactive oxygen species or/and reactive nitrogen species generation and their clearance by antioxidant protection systems. Transcription factor the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in maintaining the oxidative homeostasis by regulating multiple downstream antioxidants. The Nrf2 plays a significant role in ARE-mediated basal and inducible expression of more than 200 genes that can be grouped into numerous categories as well as antioxidant genes and phase II detoxifying enzymes. On the other hand, activation of Nrf2 by natural and synthetic therapeutics or antioxidants has been revealed effective for the prevention and treatment of toxicities and diseases connected with oxidative stress. Hence, recently focus has been shifted toward plants and plant-based medicines in curing such chronic diseases, as they are supposed to be less toxic. In this review, we focused on the role of some natural products on diabetic cardiomyopathy through Nrf2 pathway.

  8. Chronobiology of ethanol: animal models.

    Science.gov (United States)

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Diet and Diabetic Kidney Disease: Plant Versus Animal Protein.

    Science.gov (United States)

    Moorthi, Ranjani N; Vorland, Colby J; Hill Gallant, Kathleen M

    2017-03-01

    The goal of this review is to present an overview of the evidence on the effectiveness of plant-based diets in delaying progression of diabetic kidney disease (DKD). The ideal quantity of dietary protein has been a controversial topic for patients with DKD. Smaller studies have focused on protein source, plant versus animal, for preventing progression. Limited evidence suggests that dietary patterns that focus on plant-based foods, those that are lower in processed foods, or those that are lower in advanced glycation end products (AGE) may be useful in prevention of DKD progression. Increasing plant-based foods, incorporating diet patterns that limit processed foods, or potentially lowering AGE contents in diets may be beneficial for dietary management of DKD. However, dietary studies specifically targeted at DKD treatment are sparse. Further, large trials powered to assess outcomes including changes in kidney function, end-stage kidney disease, and mortality are needed to provide more substantial evidence for these diets.

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

    Directory of Open Access Journals (Sweden)

    HUANG Haiyan

    2014-09-01

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

  11. Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

    Directory of Open Access Journals (Sweden)

    Catarina Marques

    2014-01-01

    Full Text Available This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp. and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

  12. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals.

    Science.gov (United States)

    Marques, Catarina; Mega, Cristina; Gonçalves, Andreia; Rodrigues-Santos, Paulo; Teixeira-Lemos, Edite; Teixeira, Frederico; Fontes-Ribeiro, Carlos; Reis, Flávio; Fernandes, Rosa

    2014-01-01

    This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

  13. Mild Diabetes Models and Their Maternal-Fetal Repercussions

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2013-01-01

    Full Text Available The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.

  14. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

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

  15. Animal models of cerebral arterial gas embolism

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

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

  18. Animal model and neurobiology of suicide.

    Science.gov (United States)

    Preti, Antonio

    2011-06-01

    Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Molecular imaging of retinal endothelial injury in diabetic animals

    Directory of Open Access Journals (Sweden)

    Sonja Frimmel

    2017-01-01

    Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.

  20. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

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

    2013-01-01

    responses are likely to be behavioral, allowing multiple experiments in each individual animal. Distinction is made between acute and prophylactic models and how to validate each of them. Modern insight into neurobiological mechanisms of migraine is so good that it is only a question of resources...... 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...

  1. An animal model of spontaneous metabolic syndrome: Nile grass rat.

    Science.gov (United States)

    Noda, Kousuke; Melhorn, Mark I; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K C; Hafezi-Moghadam, Ali

    2010-07-01

    Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically engineered rodents, imitate certain aspects of the disease, while lacking other important components. Defining the natural course of MetS in a spontaneous animal model of the disease would be desirable. Here, we introduce the Nile grass rat (NGR), Arvicanthis niloticus, as a novel model of MetS. Studies of over 1100 NGRs in captivity, fed normal chow, revealed that most of these animals spontaneously develop dyslipidemia (P<0.01), and hyperglycemia (P<0.01) by 1 yr of age. Further characterization showed that the diabetic rats develop liver steatosis, abdominal fat accumulation, nephropathy, atrophy of pancreatic islets of Langerhans, fatty streaks in the aorta, and hypertension (P<0.01). Diabetic NGRs in the early phase of the disease develop hyperinsulinemia, and show a strong inverse correlation between plasma adiponectin and HbA1c levels (P<0.01). These data indicate that the NGR is a valuable, spontaneous model for exploring the etiology and pathophysiology of MetS as well as its various complications.

  2. Overview of Animal Models of Obesity

    Science.gov (United States)

    Lutz, Thomas A.; Woods, Stephen C.

    2012-01-01

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

  3. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2014-01-01

    Full Text Available Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

  4. Animal Models of Middle Ear Cholesteatoma

    Directory of Open Access Journals (Sweden)

    Tomomi Yamamoto-Fukuda

    2011-01-01

    Full Text Available 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 been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma.

  5. Animal models: an important tool in mycology.

    Science.gov (United States)

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

    2007-12-01

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

  6. The development of expertise: animal models?

    Science.gov (United States)

    Helton, William S

    2004-01-01

    There is a continuing debate in the psychological literature between researchers who lean more toward learning theories of expertise development and those who lean more toward talent theories. However, the development of human expertise has not been open to direct experimental methods and will probably continue to elude experimentalists in the future. A promising alternative to direct experimental methods is to use human animal models, a possibility that researchers in expertise seem to have overlooked. However, there are studies in the animal behavior literature that address the development of nonhuman animal expertise without specifically referring to the topic as expertise. In the present study, the author discusses two nonhuman animal examples of expertise development that have been researched by ethologists. Nonhuman animal expertise development, unlike human expertise development, is subject to direct experimentation. The author thus recommends that researchers use nonhuman animals in their studies of expertise.

  7. Combating Combination of Hypertension and Diabetes in Different Rat Models

    Directory of Open Access Journals (Sweden)

    Talma Rosenthal

    2010-03-01

    Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

  8. Animal Models of Chemotherapy-induced Mucositis

    DEFF Research Database (Denmark)

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

    2018-01-01

    of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g. GIT) insights, standardized, clinically-relevant treatment regimens and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM......Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression...... mangement and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients that vary according to the antineoplastic drugs, dose, underlying (cancer) disease and patient characteristics (e.g. age, genetics, body...

  9. Lessons from animal models of osteoarthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den

    2008-01-01

    Animal models of osteoarthritis (OA) provide valuable insight into pathogenetic pathways. Although OA is not an inflammatory disease, synovial activation clearly plays a role. Matrix metalloproteinases 3 (stromelysin) and 13 (collagenase) appear crucial, and a disintegrin and metalloproteinase with

  10. STRESS RESPONSE STUDIES USING ANIMAL MODELS

    Science.gov (United States)

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

  11. Animal models of cerebral amyloid angiopathy.

    Science.gov (United States)

    Jäkel, Lieke; Van Nostrand, William E; Nicoll, James A R; Werring, David J; Verbeek, Marcel M

    2017-10-15

    Cerebral amyloid angiopathy (CAA), due to vascular amyloid β (Aβ) deposition, is a risk factor for intracerebral haemorrhage and dementia. CAA can occur in sporadic or rare hereditary forms, and is almost invariably associated with Alzheimer's disease (AD). Experimental (animal) models are of great interest in studying mechanisms and potential treatments for CAA. Naturally occurring animal models of CAA exist, including cats, dogs and non-human primates, which can be used for longitudinal studies. However, due to ethical considerations and low throughput of these models, other animal models are more favourable for research. In the past two decades, a variety of transgenic mouse models expressing the human Aβ precursor protein (APP) has been developed. Many of these mouse models develop CAA in addition to senile plaques, whereas some of these models were generated specifically to study CAA. In addition, other animal models make use of a second stimulus, such as hypoperfusion or hyperhomocysteinemia (HHcy), to accelerate CAA. In this manuscript, we provide a comprehensive review of existing animal models for CAA, which can aid in understanding the pathophysiology of CAA and explore the response to potential therapies. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. 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].

  13. Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

    International Nuclear Information System (INIS)

    Dubois, E.A.; Kam, K.L.; Somsen, G.A.; Boer, G.J.; Bruin, K. de; Batink, H.D.; Pfaffendorf, M.; Royen, E.A. van; Zwieten, P.A. van

    1996-01-01

    The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [ 123 I]MIBG. Initial myocardial uptake and washout rates of [ 123 I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [ 123 I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [ 123 I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity noninvasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [ 123 I]MIBG wash-out rate was increased. Thus, either [ 123 I]MIBG washout or β-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. (orig./MG)

  14. The enduring importance of animal models in understanding periodontal disease.

    Science.gov (United States)

    Hajishengallis, George; Lamont, Richard J; Graves, Dana T

    2015-01-01

    Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets.

  15. 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.

  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. 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. Welfare...... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....

  18. 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.

  19. Oxymetazoline ototoxicity in a chinchilla animal model.

    Science.gov (United States)

    Daniel, Sam J; Akinpelu, Olubunmi V; Sahmkow, Sofia; Funnell, W Robert J; Akache, Fadi

    2012-01-01

    To investigate possible ototoxic effects of a one-time application of oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study Design. A prospective, controlled animal study. The Research Institute of the Montreal's Children Hospital, McGill University Health Centre. Ventilation tubes were inserted in both ears of 12 animals. One ear was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral ear did not receive any drops, serving as a control ear. Distortion product otoacoustic emissions were measured bilaterally for a wide range of frequencies (between 1 and 16 kHz) before and 1 day after the application of oxymetazoline in the experimental ears. Two months later, the animals were sacrificed and all cochleae were dissected out and processed for scanning electron microscopy. In this established chinchilla animal model, the measured distortion product otoacoustic emission amplitudes and the morphological appearance on scanning electron microscopy were similar for both control and experimental ears. Oxymetazoline did not cause ototoxicity in a chinchilla animal model 2 months after a single application via a tympanostomy tube.

  20. 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.

  1. Animal models for HIV cure research

    Directory of Open Access Journals (Sweden)

    Ben Bruno Policicchio

    2016-01-01

    Full Text Available 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 HIV infection will require multiple tools and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure or eliminating the reservoir altogether (sterilizing cure. Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new nonhuman primate and mouse models, along with a certain interest in the feline model, have the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.

  2. Animal Models for HIV Cure Research.

    Science.gov (United States)

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

    2016-01-01

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

  3. Experimental strategy of animal trial for the approval of anti-diabetic agents prior to their use in pre-human clinical trials

    Directory of Open Access Journals (Sweden)

    Vivek K. Bajpai

    2016-03-01

    Full Text Available Although several naturally available drugs have been historically used for the treatment of diabetes mellitus throughout the world, few of them have been validated by scientific criteria. Before approval of any drug developed it should pass through animal trial prior to clinical human trial, which should followed by some standard ethical rules. Recently, a large diversity of animal models have been developed to better understand the pathogenesis of diabetes mellitus, and new drugs have been introduced in the market to treat this autoimmune disease. In the present article, we demonstrated some standard handling procedure of animal trial for the approval of anti-diabetic drug, which could be helpful for both academics and industrial scientific community to conduct the animal experiments. This research also contributes in the field of ethnopharmacology to design new strategies for the development of novel drugs to treat this serious condition of diabetes mellitus that constitutes a global public health.

  4. Large animal models for stem cell therapy.

    Science.gov (United States)

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

    2013-03-28

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

  5. Standardization of A Physiologic Hypoparathyroidism Animal Model.

    Science.gov (United States)

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

    2016-01-01

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

  6. Standardization of A Physiologic Hypoparathyroidism Animal Model.

    Directory of Open Access Journals (Sweden)

    Soo Yeon Jung

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

  7. Development of animal models of otitis media.

    Science.gov (United States)

    Park, Moo Kyun; Lee, Byung Don

    2013-04-01

    Otitis media is defined as inflammation of the middle ear, including the auditory ossicles and the Eustachian tube. Otitis media is a major health problem in many societies. The causes of otitis media includes infection and anatomic/physiologic, host, and environmental factors. In general, otitis media is a childhood disease, and anatomic and physiologic changes have great effects on its development. Thus, in vitro or human experimental studies of otitis media are difficult. Several experimental animal models have been introduced to investigate the pathogenesis and treatment of otitis media. However, none are ideal. The aim of this review is to provide a brief overview of the current status of animal models of otitis media with effusion, acute otitis media, and cholesteatoma. This review will assist determination of the most appropriate animal models of otitis media.

  8. 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.

  9. Animal models of asthma: utility and limitations

    Directory of Open Access Journals (Sweden)

    Aun MV

    2017-11-01

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

  10. Importância do modelo animal para testar hipóteses sobre a fisiopatologia do binômio diabetes e incontinência urinária feminina = Importance of animal model to test hypotheses about the pathophysiology of the binomial diabetes and female urinary incontinence

    OpenAIRE

    Marini, Gabriela

    2011-01-01

    Objetivos: discutir a importância do estudo de modelos animais para testar hipóteses sobre os mecanismos de continência urinária e fisiopatologia do binômio diabetes incontinência urinária Fonte de Dados: foi realizada revisão de literatura no PubMed e SciELO. Os descritores utilizados foram diabetes, urinary incontinence, urethra, human e rats Síntese dos Dados: existe forte correlação entre a gênese da incontinência urinária e o diabetes mellitus. Devido à similaridade entre a distrib...

  11. Are animal models predictive for humans?

    Directory of Open Access Journals (Sweden)

    Greek Ray

    2009-01-01

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

  12. 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.

  13. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Animal models of chronic obstructive pulmonary disease.

    Science.gov (United States)

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

    2015-03-01

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

  15. Large Mammalian Animal Models of Heart Disease

    Directory of Open Access Journals (Sweden)

    Paula Camacho

    2016-10-01

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

  16. [Skin defect modeling in experimental animals].

    Science.gov (United States)

    Oleshko, A N; Kornienko, V V; Tkachenko, Yu A; Kurganskaya, V A

    2015-02-01

    To assess the skin regeneration and explore new medical devices for the treatment of skin defects is necessary to conduct long-term experiments using laboratory animals. Currently, there are many methods for skin trauma modeling but most of them have disadvantages that limit their use. The purpose of this work - the development of an experimental model of the formation of skin defect of various etiologies with the specified parameters of depth and area of damage to the absence of systemic effects on the animal's body. We have developed an installation that allows us to form a skin defect of mechanical, thermal and chemical etiology with area from 1.76 cm2 to 2.0 cm2. The experiment was conducted on 18 male laboratory rats to examine the effectiveness of current method and control the depth and area of the defect. As a result of the new methodology, we were able to carry out simulation skin injuries of different etiology on laboratory animals in the short term and reduce the severity of injuries to extend the life span of animals to monitor the repair processes, as well as to standardize the modeling of injuries according to the criteria of area and depth of the defect.

  17. 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.

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

    Science.gov (United States)

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

    2007-01-01

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

  19. Spatiotemporal epidemic models for rabies among animals

    Directory of Open Access Journals (Sweden)

    Shigui Ruan

    2017-08-01

    Full Text Available Rabies is a serious concern to public health and wildlife management worldwide. Over the last three decades, various mathematical models have been proposed to study the transmission dynamics of rabies. In this paper we provide a mini-review on some reaction-diffusion models describing the spatial spread of rabies among animals. More specifically, we introduce the susceptible-exposed-infectious models for the spatial transmission of rabies among foxes (Murray et al., 1986, the spatiotemporal epidemic model for rabies among raccoons (Neilan and Lenhart, 2011, the diffusive rabies model for skunk and bat interactions (Bonchering et al., 2012, and the reaction-diffusion model for rabies among dogs (Zhang et al., 2012. Numerical simulations on the spatiotemporal dynamics of these models from these papers are presented.

  20. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...

  1. Microparticles and cancer thrombosis in animal models.

    Science.gov (United States)

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

    2016-04-01

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

  2. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

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

  3. Animal models of age related macular degeneration

    Science.gov (United States)

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

    2013-01-01

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

  4. 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...

  5. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

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    Jang Hyun Koh

    2014-01-01

    Full Text Available The overexpression of vascular endothelial growth factor (VEGF is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10, OLETF rats as diabetic control group (n=10, and OLETF rats treated with taurine group (n=10. We treated taurine (200 mg/kg/day for 20 weeks and treated high glucose (HG, 30 mM with or without taurine (30 mM in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

  6. Animal models of compulsive eating behavior.

    Science.gov (United States)

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

    2014-10-22

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

  7. 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.

  8. Diabetes and hypertension in rodent models.

    Science.gov (United States)

    Klöting, I; Berg, S; Kovács, P; Voigt, B; Vogt, L; Schmidt, S

    1997-09-20

    As shown by ourselves and others, animals models closely resembling human complex diseases like IDDM in BB/OK and hypertension in SHR/Mol rats can be used to dissect a complex disease into discrete genetic factors as has been done for hypertension in (BB/OK x SHR/Mol) cross hybrids. Discrete genetic factors, so-called QTLs, were detected on chromosomes 1, 10, 18, 20, and X. To gain additional information about the physiologic effect of the mapped blood pressure QTLs, genetically defined regions of the SHR rat were transferred onto the genetic background of diabetes-prone BB/OK rats. Four new congenic BB.SHR rats named BB.Sa, BB.Bp2, BB.1K, and BB.Xs were generated and characterized telemetrically for blood pressure, heart rate, and motor activity. The data demonstrate clearly that each single blood pressure QTL of the SHR rat causes a significant increase of the systolic blood pressure and has a different influence on diastolic blood pressure, heart rate, and motor activity. The effects were modified differently by the diabetic state in BB.Sa, BB.Bp2, and BB.Xs rats carrying all diabetogenic genes of the BB/OK rats. The results demonstrate that these newly established congenic strains are a unique tool to study the physiological control of blood pressure by a single blood pressure QTL on the one hand and their interaction with hyperglycemia on the other. It is well within the bounds of possibility that diabetic congenics reflect the diabetic hypertension seen in diabetic patients. Because of the synteny conservation in gene order between different mammals, genes of the appropriate human region could therefore be candidate genes for hypertension in diabetics. Furthermore, these congenic strains can also be used to study interactions between a blood pressure QTL and various selected environmental conditions. In this way, one could learn which QTL can be influenced by environmental factors and to what extent. Another point is the study of gene interactions. Because

  9. Animal Models Utilized in HTLV-1 Research

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    Amanda R. Panfil

    2013-01-01

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

  10. Animal Models of Cancer-Associated Hypercalcemia.

    Science.gov (United States)

    Kohart, Nicole A; Elshafae, Said M; Breitbach, Justin T; Rosol, Thomas J

    2017-04-13

    Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.

  11. Potential animal models of seasonal affective disorder.

    Science.gov (United States)

    Workman, Joanna L; Nelson, Randy J

    2011-01-01

    Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Creating a Long-Term Diabetic Rabbit Model

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    Jianpu Wang

    2010-01-01

    Full Text Available This study was to create a long-term rabbit model of diabetes mellitus for medical studies of up to one year or longer and to evaluate the effects of chronic hyperglycemia on damage of major organs. A single dose of alloxan monohydrate (100 mg/kg was given intravenously to 20 young New Zealand White rabbits. Another 12 age-matched normal rabbits were used as controls. Hyperglycemia developed within 48 hours after treatment with alloxan. Insulin was given daily after diabetes developed. All animals gained some body weight, but the gain was much less than the age-matched nondiabetic rabbits. Hyperlipidemia, higher blood urea nitrogen and creatinine were found in the diabetic animals. Histologically, the pancreas showed marked beta cell damage. The kidneys showed significantly thickened afferent glomerular arterioles with narrowed lumens along with glomerular atrophy. Lipid accumulation in the cytoplasm of hepatocytes appeared as vacuoles. Full-thickness skin wound healing was delayed. In summary, with careful management, alloxan-induced diabetic rabbits can be maintained for one year or longer in reasonably good health for diabetic studies.

  13. An animal model to study regenerative endodontics.

    Science.gov (United States)

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

    2011-02-01

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

  14. An Alternative to the Use of Animals to Teach Diabetes Mellitus

    Science.gov (United States)

    Basso, Paulo José; Tazinafo, Lucas Favaretto; Silva, Mauro Ferreira; Rocha, Maria José Alves

    2014-01-01

    We developed an alternative approach to teach diabetes mellitus in our practical classes, replacing laboratory animals. We used custom rats made of cloth, which have a ventral zipper that allows stuffing with glass marbles to reach different weights. Three mock rats per group were placed into metabolic cages with real food and water and with test…

  15. Animal models for HIV/AIDS research

    Science.gov (United States)

    Hatziioannou, Theodora; Evans, David T.

    2015-01-01

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

  16. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

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

  17. Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models

    NARCIS (Netherlands)

    den Boer, M.; Voshol, P. J.; Kuipers, F.; Havekes, L. M.; Romijn, J. A.

    2004-01-01

    Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the

  18. Hepatic steatosis : A mediator of the metabolic syndrome. Lessons from animal models

    NARCIS (Netherlands)

    den Boer, M; Voshol, PJ; Kuipers, F; Havekes, LM; Romijn, JA

    Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the

  19. Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models

    NARCIS (Netherlands)

    Boer, M. den; Voshol, P.J.; Kuipers, F.; Havekes, L.M.; Romijn, J.A.

    2004-01-01

    Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the

  20. Development of experimental alloxan model of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    V.V. Semenko

    2017-05-01

    Full Text Available Background. One of the main causes that lead to the disability of diabetic patients is diabetic retinopathy (DR. The relevance of the problem of DR necessitates the development of optimal experimental models on experimental animals to find effective ways of correcting this pathology. The purpose of our work was to develop an experimental alloxan model of type 1 diabetes mellitus (DM for the study of DR, which would not result in the lethal outcome of experimental animals under the action of alloxan; histological examination of changes in the tissues of the eyeball in the reproduction of the DM model for the selection of new effective methods for the metabolic treatment of DR in the early stages. Materials and methods. The experiment was carried out on white outbred Wistar rats weighing 180–200 g. The first group consisted of 20 animals that were not subjected to any influence, served as a control; second group — 30 animals, in which DM was modeled by administration of alloxan and fructose. Results. When modeling DR, vessel changes in the form of wall fibrosis, edema of the endothelium and vasospasm were found. There was also a decrease in the amount of pigment granules, dystrophic changes in the cells of the ganglionic layer and a layer of retinal rods and cones, which coincides with the descriptions of damage to the coats of the eyeball in patients with DM. Conclusions. In our studies, we have calculated the optimal dose of alloxan administration, which does not lead to the death of rats (the lethality of rats was absent and is an effective model not only of DM in general, but also of DR.

  1. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

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    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.

  2. Small-Animal Models of Zika Virus.

    Science.gov (United States)

    Julander, Justin G; Siddharthan, Venkatraman

    2017-12-16

    Zika virus (ZIKV) infection can result in serious consequences, including severe congenital manifestations, persistent infection in the testes, and neurologic sequelae. After a pandemic emergence, the virus has spread to much of North and South America and has been introduced to many countries outside of ZIKV-endemic areas as infected travelers return to their home countries. Rodent models have been important in gaining a better understanding of the wide range of disease etiologies associated with ZIKV infection and for the initial phase of developing countermeasures to prevent or treat viral infections. We discuss herein the advantages and disadvantages of small-animal models that have been developed to replicate various aspects of disease associated with ZIKV infection. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Biokinetic models for radionuclides in experimental animals

    International Nuclear Information System (INIS)

    Morcillo, M. A.

    2003-01-01

    The biokinetic models for many radionuclides are, to a large extent, based on data obtained in experimental animals. The methods used in the experimental development of a biokinetic model can be classified in two groups (i) those applied during the experimental work, which include the activity determination of a given radionuclide at different times and in different biological media such as blood, serum, organs/tissues, urine, bile and faeces and (ii) those methods used for the analysis and study of the experimental data, based in mathematical tools. Some of these methods are reviewed,with special emphasis in the whole body macro autoradiography. To conclude, the contribution that this type of studies can have in two fields of radiation protection is discussed, namely optimization of dosimetric evaluations and decorporation of radionuclides. (Author)

  4. Advances in transgenic animal models and techniques.

    Science.gov (United States)

    Ménoret, Séverine; Tesson, Laurent; Remy, Séverine; Usal, Claire; Ouisse, Laure-Hélène; Brusselle, Lucas; Chenouard, Vanessa; Anegon, Ignacio

    2017-10-01

    On May 11th and 12th 2017 was held in Nantes, France, the international meeting "Advances in transgenic animal models and techniques" ( http://www.trm.univ-nantes.fr/ ). This biennial meeting is the fifth one of its kind to be organized by the Transgenic Rats ImmunoPhenomic (TRIP) Nantes facility ( http://www.tgr.nantes.inserm.fr/ ). The meeting was supported by private companies (SONIDEL, Scionics computer innovation, New England Biolabs, MERCK, genOway, Journal Disease Models and Mechanisms) and by public institutions (International Society for Transgenic Technology, University of Nantes, INSERM UMR 1064, SFR François Bonamy, CNRS, Région Pays de la Loire, Biogenouest, TEFOR infrastructure, ITUN, IHU-CESTI and DHU-Oncogeffe and Labex IGO). Around 100 participants, from France but also from different European countries, Japan and USA, attended the meeting.

  5. 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.

  6. Impact of Diabetes Education Based on Type 1 Diabetes management model

    OpenAIRE

    Ocakçı, Ayşe Ferda

    2015-01-01

    The diabetes management is considered to be adversely affected when adolescent-specific education methods are not used. In this study, Type 1 Diabetes Management Model which ensures standardisation of the diabetes education and is based on the health promotion model and formed by applying health promotion model (HPM) according to the mastery-learning theory was used. The study was performed to determine effectiveness of diabetes education based on “Type 1 Diabetes Management Model” on adolesc...

  7. Exploring the role of the HNF-1αG319S polymorphism in β cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models.

    Science.gov (United States)

    Jonasson, Michael E; Wicklow, Brandy A; Sellers, Elizabeth A C; Dolinsky, Vernon W; Doucette, Christine A

    2015-10-01

    The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and private polymorphism in the Oji-Cree population in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene, where a highly conserved glycine residue at position 319 is changed to a serine (termed HNF-1αG319S or simply G319S). Oji-Cree youth who carry one or two copies of the "S-allele" present at diagnosis with less obesity, reduced indicators of insulin resistance, and lower plasma insulin levels at diagnosis, suggestive of a primary defect in the insulin-secreting β cells. Few studies on the impact of the HNF-1αG319S variant on β cell function have been performed to date; however, much can be learned from other clinical phenotypes of HNF-1α-deficiency, including HNF-1α mutations that cause maturity-onset diabetes of the young 3 (MODY3). In addition, evaluation of Hnf-1α-deficient murine models reveals that HNF-1α plays a central role in the regulation of insulin secretion by regulating the expression of key genes involved in β cell glucose-sensing, mitochondrial function, and the maintenance of the β cell phenotype in differentiated β cells. The overall goal of this minireview is to explore the impact of HNF-1α-deficiency on the β cell to better inform future research into the mechanisms of β cell dysfunction in Oji-Cree youth with T2D.

  8. [Analysis of dalbavancin in animal models].

    Science.gov (United States)

    Murillo, Óscar; El-Haj, Cristina

    2017-01-01

    Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  9. 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

  10. Neuroprotective and nootropic activity of Clitorea ternatea Linn.(Fabaceae leaves on diabetes induced cognitive decline in experimental animals

    Directory of Open Access Journals (Sweden)

    Karuna A Talpate

    2014-01-01

    Full Text Available Purpose: Ethanol extract of Clitorea ternatea (EECT was evaluated in diabetes-induced cognitive decline rat model for its nootropic and neuroprotective activity. Materials and Methods: Effect on spatial working memory, spatial reference memory and spatial working-reference memory was evaluated by Y maze, Morris water maze and Radial arm maze respectively. Neuroprotective effects of EECT was studied by assaying acetylcholinesterase, lipid peroxide, superoxide dismutase (SOD, total nitric oxide (NO, catalase (CAT and glutathione (GSH levels in the brain of diabetic rats. Results: The EECT (200 and 400 mg/kg was found to cause significant increase in spatial working memory ( P < 0.05, spatial reference memory ( P < 0.001 and spatial working-reference ( P < 0.001 in retention trials on Y maze, Morris water maze and Radial arm maze respectively. Whereas significant decrease in acetylcholinesterase activity ( P < 0.05, lipid peroxide ( P < 0.001, total NO ( P < 0.001 and significant increase in SOD, CAT and GSH levels was observed in animals treated with EECT (200 and 400 mg/kg compared to diabetic control group. Conclusions: The present data indicates that Clitorea ternatea tenders protection against diabetes induced cognitive decline and merits the need for further studies to elucidate its mode of action.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Alterations of urinary metabolite profile in model diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  13. Alterations of urinary metabolite profile in model diabetic nephropathy

    International Nuclear Information System (INIS)

    Stec, Donald F.; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

    2015-01-01

    Highlights: • 1 H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in

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

    Directory of Open Access Journals (Sweden)

    Mohan Kumar Pasupuleti

    2016-01-01

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

  15. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

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

    1998-01-01

    Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution

  16. 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.

  17. Validation of the IMS CORE Diabetes Model.

    Science.gov (United States)

    McEwan, Phil; Foos, Volker; Palmer, James L; Lamotte, Mark; Lloyd, Adam; Grant, David

    2014-09-01

    The IMS CORE Diabetes Model (CDM) is a widely published and validated simulation model applied in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) analyses. Validation to external studies is an important part of demonstrating model credibility. Because the CDM is widely used to estimate long-term clinical outcomes in diabetes patients, the objective of this analysis was to validate the CDM to contemporary outcomes studies, including those with long-term follow-up periods. A total of 112 validation simulations were performed, stratified by study follow-up duration. For long-term results (≥15-year follow-up), simulation cohorts representing baseline Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) cohorts were generated and intensive and conventional treatment arms were defined in the CDM. Predicted versus observed macrovascular and microvascular complications and all-cause mortality were assessed using the coefficient of determination (R(2)) goodness-of-fit measure. Across all validation studies, the CDM simulations produced an R(2) statistic of 0.90. For validation studies with a follow-up duration of less than 15 years, R(2) values of 0.90 and 0.88 were achieved for T1DM and T2DM respectively. In T1DM, validating against 30-year outcomes data (DCCT) resulted in an R(2) of 0.72. In T2DM, validating against 20-year outcomes data (UKPDS) resulted in an R(2) of 0.92. This analysis supports the CDM as a credible tool for predicting the absolute number of clinical events in DCCT- and UKPDS-like populations. With increasing incidence of diabetes worldwide, the CDM is particularly important for health care decision makers, for whom the robust evaluation of health care policies is essential. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Ambalavanan, Namasivayam; Morty, Rory E

    2016-11-01

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

  19. [Genetic mice models of type 2 diabetes for evaluation of the effectiveness of minor biologically active food substances].

    Science.gov (United States)

    Mazo, V K; Sidorova, Yu S; Kochetkova, A A

    2015-01-01

    This report is devoted to discussion of type 2 diabetes experimental modelling on genetic mice lines. These laboratory animals, the same as genetic rats lines, are usually used in type 2 diabetes experimental modelling. The problem of using mice with genetic obesity in modeling of type 2 diabetes is discussed in details in the review. In this article the authors shortly characterize the congenic line of mice ККАУ, suffering from genetic obesity and hyperinsulinemia. The features of modelling type 2 diabetes using ob/ob and db/db mice are described closely. The phenotype of the animals comes into obesity, infertility, brakes in length growth, hyperinsulinemia and dysimmunity. Neither leptin mRNA, nor the hormone itself are synthesized in ob/ob mice, leading to ob phenotype formation. Whilst db/db mice have two mutant copies of leptin receptor gene, which leads to gradual hyperglycemia and obesity progression, followed by hyperinsulemia similar to human type 2 diabetes. C57BL/KsLeprdb/+ mice with recessive gene leptin receptoi-Lepiнlb (db) is very perspective genetic type 2 diabetes model developed in Russia. TSOD mice are used as an alternative model (Tsumura Suzuki, diabetes with obesity), showing diabetes and obesity symptoms with marked hyperinsulinemia and pancreatic gland hypertrophy. Thus, presented in this review scientific reports approve wide opportunities of effective usage of genetic lines of small laboratory animals (mice) for type 2 diabetes modelling.

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

    Science.gov (United States)

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

    2009-01-01

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

  1. Digital creature creation: applied 3D modelling and animation for Australian animal visualization

    OpenAIRE

    Ung, Chandara

    2017-01-01

    This exegesis focuses on the investigative and studio research informing the digital construction of a diverse selection of Australian animals. A series of case studies of digital creature construction - the Jackie Dragon, Jabiru, Bandicoot, Eel, Blue Ringed Octopus and Fiddler Crab - will be outlined along with the key creation study of the Groper. Through investigating how visual research can inform the creation of 3D modelled and animated animal subjects and tracing their development proce...

  2. Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

    OpenAIRE

    SA Lanham; C Bertram; C Cooper; ROC Oreffo

    2011-01-01

    It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspr...

  3. 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

  4. Animales de laboratorio en la endocrinología: Biomodelos de la diabetes mellitus tipo 1 Laboratory animals in endocrinology: Biomodels of type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Beatriz Hugues Hernandorena

    2001-12-01

    Full Text Available En las investigaciones biomédicas se precisa la utilización de los animales de laboratorio como biomodelos naturales o inducidos de diversas enfermedades o procesos morbosos, los cuales ayudan al estudio y la comprensión de la patogenia, fisiología y posibilidades de tratamiento de las mismas. En la endocrinología se utilizan para estudiar estos aspectos de las enfermedades de origen autoinmune o no relacionadas con este sistema, como la diabetes mellitus, disfunciones tiroideas, trastornos de la reproducción y del metabolismo, entre otras, además de constituir un arma importante para investigar las interrelaciones hormonales que ocurren en los individuos normales o enfermos. Se realizó una amplia revisión bibliográfica sobre el tema para brindar una información detallada sobre los modelos animales de diabetes mellitus tipo 1 utilizados en las investigaciones biomédicas, que comprendiera los que se obtienen de forma espontánea e inducida, así como la influencia sobre ellos, de los factores ambientales. Se concluyó que resulta de vital importancia para el logro de las investigaciones básicas in vivo mantener un control estricto de las condiciones ambientales en las que desarrollamos nuestras investigaciones y ampliar nuestros conocimientos sobre el tema.In biomedical research, it is necessary the use of laboratory animals as natural or induced models of different diseases or morbid processes that make easy the study and understanding of the pathogeny, physiology and possibilities of treatment of them. In endocrinology, they are utilized to study the aspects of the diseases of autoimmune origin or of those not related to this system, such as diabetes mellitus, thyroid dysfunctions, reproduction and metabolism disorders, among others. Besides, they are also an important tool to investigate the hormonal interrelations occurring in normal or sick individuals. A wide bibliographic review on this topic was made to give a detailed

  5. 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.

  6. MODELING OF ANIMATED SIMULATIONS BY MAXIMA PROGRAM TOOLS

    Directory of Open Access Journals (Sweden)

    Nataliya O. Bugayets

    2015-06-01

    Full Text Available The article deals with the methodical features in training of computer simulation of systems and processes using animation. In the article the importance of visibility of educational material that combines sensory and thinking sides of cognition is noted. The concept of modeling and the process of building models has been revealed. Attention is paid to the development of skills that are essential for effective learning of animated simulation by visual aids. The graphical environment tools of the computer mathematics system Maxima for animated simulation are described. The examples of creation of models animated visual aids and their use for the development of research skills are presented.

  7. Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.

    Science.gov (United States)

    Lovati, Arianna B; Drago, Lorenzo; Monti, Lorenzo; De Vecchi, Elena; Previdi, Sara; Banfi, Giuseppe; Romanò, Carlo L

    2013-01-01

    Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3) colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy). Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.

  8. Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Arianna B Lovati

    Full Text Available BACKGROUND: Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. METHODOLOGY: A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3 colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count, histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy. RESULTS: Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. CONCLUSIONS: Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.

  9. Hair corticosterone measurement in mouse models of type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Erickson, Rebecca L; Browne, Caroline A; Lucki, Irwin

    2017-09-01

    In diabetes, glucocorticoid secretion increases secondary to hyperglycemia and is associated with an extensive list of disease complications. Levels of cortisol in humans, or corticosterone in rodents, are usually measured as transitory biomarkers of stress in blood or saliva. Glucocorticoid concentrations accumulate in human or animal hair over weeks and could more accurately measure the cumulative stress burden of diseases like chronic diabetes. In this study, corticosterone levels were measured in hair in verified rodent models of diabetes mellitus. To induce type 1 diabetes, C57BL/6J mice were injected with streptozotocin and blood and hair samples were collected 28days following induction. Leptin receptor deficient (db/db) mice were used as a spontaneous model of type 2 diabetes and blood and hair samples were collected at 8weeks of age, after the development of hyperglycemia and obesity. Corticosterone levels from serum, new growth hair and total growth hair were analyzed using an enzyme immunoassay. Corticosterone levels in new growth hair and serum were significantly elevated in both models of diabetes compared to controls. In contrast, corticosterone levels in old hair growth did not differ significantly between diabetic and non-diabetic animals. Thus, hair removal and sampling of new hair growth was a more sensitive procedure for detecting changes in hair corticosterone levels induced by periods of hyperglycemia lasting for 4weeks in mice. These results validate the use of hair to measure long-term changes in corticosterone induced by diabetes in rodent models. Further studies are now needed to validate the utility of hair cortisol as a tool for measuring the stress burden of individuals with diabetes and for following the effects of long-term medical treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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...

  11. Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion.

    Science.gov (United States)

    Arimura, Emi; Pulong, Wijang Pralampita; Marchianti, Ancah Caesarina Novi; Nakakuma, Miwa; Abe, Masaharu; Ushikai, Miharu; Horiuchi, Masahisa

    2017-02-01

    We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice. In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured. The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels. High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

  12. Translational value of animal models of obesity-Focus on dogs and cats.

    Science.gov (United States)

    Osto, Melania; Lutz, Thomas A

    2015-07-15

    A prolonged imbalance between a relative increase in energy intake over a decrease in energy expenditure results in the development of obesity; extended periods of a positive energy balance eventually lead to the accumulation of abnormally high amounts of fat in adipose tissue but also in other organs. Obesity is considered a clinical state of impaired general heath in which the excessive increase in adipose tissue mass may be associated with metabolic disorders such as type 2 diabetes mellitus, hyperlipidemia, hypertension and cardiovascular diseases. This review discusses briefly the use of animal models for the study of obesity and its comorbidities. Generally, most studies are performed with rodents, such as diet induced obesity and genetic models. Here, we focus specifically on two different species, namely dogs and cats. Obese dogs and cats show many features of human obesity. Interestingly, however, dogs and cats differ from each other in certain aspects because even though obese dogs may become insulin resistant, this does not result in the development of diabetes mellitus. In fact, diabetes in dogs is typically not associated with obesity because dogs present a type 1 diabetes-like syndrome. On the other hand, obese cats often develop diabetes mellitus which shares many features with human type 2 diabetes; feline and human diabetes are similar in respect to their pathophysiology, underlying risk factors and treatment strategies. Our review discusses genetic and endocrine factors in obesity, discusses obesity induced changes in lipid metabolism and includes some recent findings on the role of gut microbiota in obesity. Compared to research in rodent models, the array of available techniques and tools is unfortunately still rather limited in dogs and cats. Hence, even though physiological and pathophysiological phenomena are well described in dogs and cats, the underlying mechanisms are often not known and studies investigating causality specifically are

  13. The Use of Animal Models in Behavioural Neuroscience Research

    NARCIS (Netherlands)

    Bovenkerk, B.; Kaldewaij, F.

    2015-01-01

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

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

    NARCIS (Netherlands)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

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

  15. Stress and adaptation : Toward ecologically relevant animal models

    NARCIS (Netherlands)

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

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

  16. 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.

  17. Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Charlotte Berg Holt

    2015-01-01

    Full Text Available Background. The innate immune system may have adverse effects in diabetes and cardiovascular disease. The complement system seems to play a key role through erroneous complement activation via hyperglycaemia-induced neoepitopes. Recently mannan-binding lectin (MBL was shown to worsen diabetic kidney changes. We hypothesize that mouse ficolin B exerts detrimental effects in the diabetic kidney as seen for MBL. Methods. We induced diabetes with streptozotocin in female wild-type mice and ficolin B knockout mice and included two similar nondiabetic groups. Renal hypertrophy and excretion of urinary albumin and creatinine were quantified to assess diabetic kidney damage. Results. In the wild-type groups, the kidney weighed 24% more in the diabetic mice compared to the controls. The diabetes-induced increase in kidney weight was 29% in the ficolin B knockout mice, that is, equal to wild-type animals (two-way ANOVA, P=0.60. In the wild-type mice the albumin-to-creatinine ratio (ACR was 32.5 mg/g higher in the diabetic mice compared to the controls. The difference was 62.5 mg/g in the ficolin B knockout mice, but this was not significantly different from the wild-type animals (two-way ANOVA, P=0.21. Conclusions. In conclusion, the diabetes-induced effects on kidney weight and ACR were not modified by the presence or absence of ficolin B.

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

    Science.gov (United States)

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

    2016-10-01

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

  19. Animales de experimentación como modelos de la diabetes mellitus tipo 2 Laboratory animals in endocrinology. Biomodels of type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Beatriz Hugués Hernandorena

    2002-08-01

    Full Text Available Se sabe que los modelos animales utilizados en las investigaciones sobre la diabetes mellitus tipo 2 (DM2, ayudan al estudio de los mecanismos patogénicos que conducen a la presentación de esta enfermedad, acompañada de severa o moderada hiperglucemia, intolerancia a la glucosa y otras alteraciones metabólicas relacionadas con la misma, y dan la oportunidad de explorar nuevos tratamientos y formas de prevenir estos cuadros morbosos. Se brindó información detallada sobre los biomodelos de la DM2, a partir de una revisión bibliográfica sobre el tema, que comprendió los que se originan espontáneamente y los que se logran de forma inducida. Se expusieron los factores ambientales que influyen sobre los mismos, y se describieron aquellos en los que se pueden presentar complicaciones crónicas de la diabetes mellitus no insulinodependiente. Se concluyó que estos biomodelos contribuyen al estudio de los mecanismos que originan esa afección y son de gran utilidad para los investigadores de esta rama de la Endocrinología, aunque no constituyan un reflejo exacto de esta enfermedad en el hombre.It is known that the animal models used in the research of type 2 diabetes mellitus help to study the pathogenic mechanisms leading to the presentation of this disease, accompanied of severe or moderate hyperglycaemia, glucose intolerance and other metabolic alterations related to it, and give the opportunity to explore new treatments and ways of preventing these morbid clinical pictures. Detailed information is given on the biomodels of type 2 diabetes mellitus based on a bibliographic review made on this topic that included those which are spontaneously originated and the ones obtained in an induced way. The environmental factors influencing on them are explained and the biomodels that may present chronic complications of non-insulin dependent diabetes mellitus are also described. It was concluded that these biomodels contribute to the study of the

  20. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

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

  1. Mathematical models of behavior of individual animals.

    Science.gov (United States)

    Tsibulsky, Vladimir L; Norman, Andrew B

    2007-01-01

    This review is focused on mathematical modeling of behaviors of a whole organism with special emphasis on models with a clearly scientific approach to the problem that helps to understand the mechanisms underlying behavior. The aim is to provide an overview of old and contemporary mathematical models without complex mathematical details. Only deterministic and stochastic, but not statistical models are reviewed. All mathematical models of behavior can be divided into two main classes. First, models that are based on the principle of teleological determinism assume that subjects choose the behavior that will lead them to a better payoff in the future. Examples are game theories and operant behavior models both of which are based on the matching law. The second class of models are based on the principle of causal determinism, which assume that subjects do not choose from a set of possibilities but rather are compelled to perform a predetermined behavior in response to specific stimuli. Examples are perception and discrimination models, drug effects models and individual-based population models. A brief overview of the utility of each mathematical model is provided for each section.

  2. Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes

    Directory of Open Access Journals (Sweden)

    Liheng Shi

    2014-01-01

    Full Text Available Diabetic retinopathy (DR is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ, high concentration of glucose (high-glucose, or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4, and phosphorylated protein kinase B (pAKT. In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC currents, which was reflected in the decreased level of L-VGCCα1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes.

  3. 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.

  4. Animal Models of Hemophilia and Related Bleeding Disorders

    Science.gov (United States)

    Lozier, Jay N.; Nichols, Timothy C.

    2013-01-01

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

  5. Time series sightability modeling of animal populations.

    Directory of Open Access Journals (Sweden)

    Althea A ArchMiller

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

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

    Science.gov (United States)

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

    2011-04-01

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

  7. Time series sightability modeling of animal populations

    Science.gov (United States)

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

    2018-01-01

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

  8. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

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

    2017-07-01

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

  9. Animals

    International Nuclear Information System (INIS)

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

    1997-01-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)

  10. Recent advances in animal model experimentation in autism research.

    Science.gov (United States)

    Tania, Mousumi; Khan, Md Asaduzzaman; Xia, Kun

    2014-10-01

    Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism. We have reviewed the publications over the last three decades, which are related to animal model study in autism. Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism. In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

  11. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    to be the prime model of inherited human disease and share 99% of their ... disturbances (including anxiety and depression) ..... Leibovici M, Safieddine S, Petit C (2008). Mouse models for human hereditary deafness. Curr. Top. Dev. Biol. 84:385-429. Levi YF, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami.

  12. 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

  13. Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview.

    Science.gov (United States)

    Goldani, Luciano Z; Wirth, Fernanda

    2017-08-01

    Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.

  14. Progression of Diabetic Capillary Occlusion: A Model.

    Directory of Open Access Journals (Sweden)

    Xiao Fu

    2016-06-01

    Full Text Available An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

  15. Epidemiological models to support animal disease surveillance activities

    DEFF Research Database (Denmark)

    Willeberg, Preben; Paisley, Larry; Lind, Peter

    2011-01-01

    Epidemiological models have been used extensively as a tool in improving animal disease surveillance activities. A review of published papers identified three main groups of model applications: models for planning surveillance, models for evaluating the performance of surveillance systems...... and models for interpreting surveillance data as part of ongoing control or eradication programmes. Two Danish examples are outlined. The first illustrates how models were used in documenting country freedom from disease (trichinellosis) and the second demonstrates how models were of assistance in predicting...

  16. Animal models for periodontal regeneration and peri-implant responses.

    Science.gov (United States)

    Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

    2015-06-01

    Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

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

  18. Animal models for testing anti-prion drugs.

    Science.gov (United States)

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

    2013-01-01

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

  19. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

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

  20. How multiple sclerosis is related to animal illness, stress and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Warren, S.A.; Warren, K.G.; Greenhill, S.; Paterson, M.

    1982-02-15

    At the University of Alberta's multiple sclerosis research clinic 100 patients with multiple sclerosis were matched to control patients for age, sex, race and zone of residence before the age of 15 years. Case and control subjects were interviewed and information was collected by questionnaire on factors that might play a role in the development of multiple sclerosis. The only factors found to be significantly associated with the development of this disorder were a history of leisure time spent in physical activities before the onset of symptoms, exposure to animal illness -- specifically canine distemper -- and a history of severe or prolonged emotional stress. The study also confirmed a familial predisposition to multiple sclerosis and suggested a relation between the disorder and a personal or family history of diabetes mellitus.

  1. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration

    Directory of Open Access Journals (Sweden)

    Valeria Colafrancesco

    2011-01-01

    Full Text Available The aim of this study was to investigate the effect of nerve growth factor (NGF administration on retinal ganglion cells (RGCs in experimentally induced glaucoma (GL and diabetic retinopathy (DR. GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye and diabetes (DT was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.

  2. Modeling animal movements using stochastic differential equations

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

  4. 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.

  5. Advances in Animal Models of Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhang Hang

    2015-12-01

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

  6. Animal models for evaluation of oral delivery of biopharmaceuticals

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  7. Albino mice as an animal model for infantile nystagmus syndrome

    NARCIS (Netherlands)

    D.L. Traber (Daniel); C.-C. Chen (Chien-Cheng); Y.-Y. Huang (Ying-Yu); M. Spoor (Monique); J. Roos (Jeanine); M.A. Frens (Maarten); D. Straumann (Dominik); C. Grimm (Christian)

    2012-01-01

    textabstractPURPOSE. Individuals with oculocutaneous albinism are predisposed to visual system abnormalities affecting the retina and retinofugal projections, which may lead to reduced visual acuity and Infantile Nystagmus Syndrome (INS). Due to absence of an established mammalian animal model,

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

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

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

  9. 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;

  10. 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. ...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...

  11. Reflected stochastic differential equation models for constrained animal movement

    Science.gov (United States)

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

    2017-01-01

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

  12. Proteomics in farm animals models of human diseases.

    Science.gov (United States)

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

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

  14. Large animal models for vaccine development and testing.

    Science.gov (United States)

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

    2015-01-01

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

  15. Nonhuman Primate Models of Type 1 Diabetes Mellitus for Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Haitao Zhu

    2014-01-01

    Full Text Available Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM. Animal models of diabetes mellitus (DM contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG, relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation.

  16. 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...

  17. 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.

  18. Cytomegalovirus Antivirals and Development of Improved Animal Models

    Science.gov (United States)

    McGregor, Alistair; Choi, K. Yeon

    2015-01-01

    Introduction Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a life long asymptomatic infection in healthy individuals. Infection of immunesuppressed individuals causes serious illness. Transplant and AIDS patients are highly susceptible to CMV leading to life threatening end organ disease. Another vulnerable population is the developing fetus in utero, where congenital infection can result in surviving newborns with long term developmental problems. There is no vaccine licensed for CMV and current antivirals suffer from complications associated with prolonged treatment. These include drug toxicity and emergence of resistant strains. There is an obvious need for new antivirals. Candidate intervention strategies are tested in controlled pre-clinical animal models but species specificity of HCMV precludes the direct study of the virus in an animal model. Areas covered This review explores the current status of CMV antivirals and development of new drugs. This includes the use of animal models and the development of new improved models such as humanized animal CMV and bioluminescent imaging of virus in animals in real time. Expert Opinion Various new CMV antivirals are in development, some with greater spectrum of activity against other viruses. Although the greatest need is in the setting of transplant patients there remains an unmet need for a safe antiviral strategy against congenital CMV. This is especially important since an effective CMV vaccine remains an elusive goal. In this capacity greater emphasis should be placed on suitable pre-clinical animal models and greater collaboration between industry and academia. PMID:21883024

  19. The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Patricia Bogdanov

    Full Text Available BACKGROUND: To characterize the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse. METHODS: C57BLKsJ-db/db mice were used as spontaneous type 2 diabetic animal model, and C57BLKsJ-db/+ mice served as the control group. To assess the chronological sequence of the abnormalities the analysis was performed at different ages (8, 16 and 24 weeks. The retinas were evaluated in terms of morphological and functional abnormalities [electroretinography (ERG]. Histological markers of neurodegeneration (glial activation and apoptosis were evaluated by immunohistochemistry. In addition glutamate levels and glutamate/aspartate transporter (GLAST expression were assessed. Furthermore, to define gene expression changes associated with early diabetic retinopathy a transcriptome analyses was performed at 8 week. Furthermore, an additional interventional study to lower blood glucose levels was performed. RESULTS: Glial activation was higher in diabetic than in non diabetic mice in all the stages (p<0.01. In addition, a progressive loss of ganglion cells and a significant reduction of neuroretinal thickness were also observed in diabetic mice. All these histological hallmarks of neurodegeneration were less pronounced at week 8 than at week 16 and 24. Significant ERG abnormalities were present in diabetic mice at weeks 16 and 24 but not at week 8. Moreover, we observed a progressive accumulation of glutamate in diabetic mice associated with an early downregulation of GLAST. Morphological and ERG abnormalities were abrogated by lowering blood glucose levels. Finally, a dysregulation of several genes related to neurotransmission and oxidative stress such as UCP2 were found at week 8. CONCLUSIONS: Our results suggest that db/db mouse reproduce the features of the neurodegenerative process that occurs in the human diabetic eye. Therefore, it seems an appropriate model for investigating the

  20. 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.

  1. Sex differences in animal models of psychiatric disorders

    Science.gov (United States)

    Kokras, N; Dalla, C

    2014-01-01

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

  2. Animal models for the study of hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Wei-Na Guo

    2018-01-01

    Full Text Available Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus (HBV worldwide. Current antiviral therapies, including interferon and nucleot(side analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.

  3. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

    Directory of Open Access Journals (Sweden)

    Robert Nunan

    2014-11-01

    Full Text Available The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

  4. Animal models of pulmonary emphysema: a stereologist's perspective

    Directory of Open Access Journals (Sweden)

    H. Fehrenbach

    2006-12-01

    Full Text Available A variety of animal models have been suggested as models of pulmonary emphysema; these are critically discussed in the present article from a stereologist's perspective. In addition, a stereological design for the quantification of experimentally induced emphysema is proposed. On the basis of the widely accepted definition of pulmonary emphysema being an "abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls," quantitative morphology is the only method with which to reliably assess the presence of emphysema. Recognising this, careful inspection of animal models that are based on instillation of elastase, genetic alterations, inhalation of cigarette smoke or induction of apoptosis, reveals that both criteria of emphysema definition were demonstrated in surprisingly few of them. Several aspects are suggested to be critical for the understanding of animal models of human emphysema. For example, genetic models that rely on the inhibition of the formation of alveoli during post-natal alveolarisation should clearly be distinguished from models that rely on the loss of mature alveoli after alveolarisation is complete. Furthermore, inhalation models that are characterised by exposed animals exhibiting a severe loss of body weight should carefully examine the relative contribution of intervention and weight loss, respectively. Models that rely on the exposure of juvenile animals for several weeks or even months should take into account the effects of normal lung growth and ageing. Stereology offers appropriate tools with which to quantify the parameters relevant to assess development and the regeneration of emphysema. Stereologists continue to develop tools that will help ascertain the reliability of established and new models. If inappropriate parameters continue to be used for the evaluation of animal models of emphysema, thinking and resources are likely to be misdirected and the

  5. Elementary of animal model for percutaneous and ocular penetration

    Directory of Open Access Journals (Sweden)

    Kalpesh Chhotalal Ashara

    2016-12-01

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

  6. Models of 'obesity' in large animals and birds.

    Science.gov (United States)

    Clarke, Iain J

    2008-01-01

    Most laboratory-based research on obesity is carried out in rodents, but there are a number of other interesting models in the animal kingdom that are instructive. This includes domesticated animal species such as pigs and sheep, as well as wild, migrating and hibernating species. Larger animals allow particular experimental manipulations that are not possible in smaller animals and especially useful models have been developed to address issues such as manipulation of fetal development. Although some of the most well-studied models are ruminants, with metabolic control that differs from monogastrics, the general principles of metabolic regulation still pertain. It is possible to obtain much more accurate endocrine profiles in larger animals and this has provided important data in relation to leptin and ghrelin physiology. Genetic models have been created in domesticated animals through selection and these complement those of the laboratory rodent. This short review highlights particular areas of research in domesticated and wild species that expand our knowledge of systems that are important for our understanding of obesity and metabolism.

  7. Flavonoid rich fraction of Punica granatum improves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

    Science.gov (United States)

    Ankita, Patel; Deepti, Bandawane; Nilam, Mhetre

    2015-01-01

    Different parts of Punica granatum Linn. (Punicaceae) are traditionally used as renal protective agents in the Indian system of medicine. However, there is paucity of information regarding its role in diabetic nephropathy. The present study investigates the nephroprotective potential of flavonoid-rich fraction of P. granatum leaves in streptozotocin (STZ)-induced early diabetic nephropathy in experimental animals. Experimental diabetic nephropathy was induced in Wistar rats by single intraperitonial injection of STZ (65 mg/kg) dissolved in ice cold citrophosphate buffer (pH 4.3). After induction rats were divided into five groups (6 normal; 24 diabetic) and administered with glibenclamide (5 mg/kg) and three dose levels of flavonoid-rich fraction of P. granatum leaves (PGFF), i.e. 50, 100, and 200 mg/kg body weight/day for 28 d. Fasting blood glucose, lipid profile, serum albumin, serum total protein, serum creatinine, blood urea nitrogen (BUN) glycosylated hemoglobin, and biomarkers of kidney oxidative stress were assessed at the end of the treatment period. Urine was analyzed for the measurement of total protein, albumin, and creatinine clearance. Kidney sections were subjected to histopathological study. Daily oral administration of variable dose levels of PGFF for 28 d normalized various biochemical, metabolic, and histopathological changes in the diabetic rats. PGFF significantly (p < 0.01 and p < 0.05) improved the glycemic status and renal function in diabetic rats as compared with diabetic control rats. The results of our study thus prove the protective effect of PGFF in early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

  8. OBESITY AND CRITICAL ILLNESS: INSIGHTS FROM ANIMAL MODELS.

    Science.gov (United States)

    Mittwede, Peter N; Clemmer, John S; Bergin, Patrick F; Xiang, Lusha

    2016-04-01

    Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models, is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

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

    DEFF Research Database (Denmark)

    Glud, A. N.; Bech, J.; Tvilling, L.

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Earl, Julia E; Zollner, Patrick A

    2017-09-01

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

  12. Animal models for the study of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Eliza Miszczyk

    2014-05-01

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

  13. Th17 in Animal Models of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Motomu Hashimoto

    2017-07-01

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

  14. Th17 in Animal Models of Rheumatoid Arthritis.

    Science.gov (United States)

    Hashimoto, Motomu

    2017-07-21

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

  15. Animal Models for Tuberculosis in Translational and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Lingjun Zhan

    2017-05-01

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

  16. 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.

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

    Science.gov (United States)

    Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis

    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 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. PMID:23754973

  18. Animal Models for Tuberculosis in Translational and Precision Medicine.

    Science.gov (United States)

    Zhan, Lingjun; Tang, Jun; Sun, Mengmeng; Qin, Chuan

    2017-01-01

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

  19. Animal Models for the Study of Female Sexual Dysfunction

    Science.gov (United States)

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

    2017-01-01

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

  20. 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

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

    African Journals Online (AJOL)

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

  2. An animal model to train Lichtenstein inguinal hernia repair

    DEFF Research Database (Denmark)

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

    2013-01-01

    pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation...

  3. Obsessive-compulsive disorder: Insights from animal models.

    Science.gov (United States)

    Szechtman, Henry; Ahmari, Susanne E; Beninger, Richard J; Eilam, David; Harvey, Brian H; Edemann-Callesen, Henriette; Winter, Christine

    2017-05-01

    Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Chest compressions in newborn animal models: A review.

    Science.gov (United States)

    Solevåg, Anne Lee; Cheung, Po-Yin; Lie, Helene; O'Reilly, Megan; Aziz, Khalid; Nakstad, Britt; Schmölzer, Georg Marcus

    2015-11-01

    Much of the knowledge about the optimal way to perform chest compressions (CC) in newborn infants is derived from animal studies. The objective of this review was to identify studies of CC in newborn term animal models and review the evidence. We also provide an overview of the different models. MEDLINE, EMBASE and CINAHL, until September 29th 2014. Study eligibility criteria and interventions: term newborn animal models where CC was performed. Based on 419 retrieved studies from MEDLINE and 502 from EMBASE, 28 studies were included. No additional studies were identified in CINAHL. Most of the studies were performed in pigs after perinatal transition without long-term follow-up. The models differed widely in methodological aspects, which limits the possibility to compare and synthesize findings. Studies uncommonly reported the method for randomization and allocation concealment, and a limited number were blinded. Only the evidence in favour of the two-thumb encircling hands technique for performing CC, a CC to ventilation ratio of 3:1; and that air can be used for ventilation during CC; was supported by more than one study. Animal studies should be performed and reported with the same rigor as in human randomized trials. Good transitional and survival models are needed to further increase the strength of the evidence derived from animal studies of newborn chest compressions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. How animal models inform child and adolescent psychiatry.

    Science.gov (United States)

    Stevens, Hanna E; Vaccarino, Flora M

    2015-05-01

    Every available approach should be used to advance the field of child and adolescent psychiatry. Biological systems are important for the behavioral problems of children. Close examination of nonhuman animals and the biology and behavior that they share with humans is an approach that must be used to advance the clinical work of child psychiatry. We review here how model systems are used to contribute to significant insights into childhood psychiatric disorders. Model systems have not only demonstrated causality of risk factors for psychiatric pathophysiology, but have also allowed child psychiatrists to think in different ways about risks for psychiatric disorders and multiple levels that might be the basis of recovery and prevention. We present examples of how animal systems are used to benefit child psychiatry, including through environmental, genetic, and acute biological manipulations. Animal model work has been essential in our current thinking about childhood disorders, including the importance of dose and timing of risk factors, specific features of risk factors that are significant, neurochemistry involved in brain functioning, molecular components of brain development, and the importance of cellular processes previously neglected in psychiatric theories. Animal models have clear advantages and disadvantages that must be considered for these systems to be useful. Coupled with increasingly sophisticated methods for investigating human behavior and biology, animal model systems will continue to make essential contributions to our field. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. Model for clinical management using body mass index of diabetes ...

    African Journals Online (AJOL)

    from the University of Ilorin Teaching Hospital on the management of diabetes. Weight was partitioned into three groups: underweight, normal weight and overweight. Three models were used for comparison: a model that used weight of diabetes patient as a covariate, a second that used both weight and admitting blood ...

  9. The use of animal models in behavioural neuroscience research.

    Science.gov (United States)

    Bovenkerk, Bernice; Kaldewaij, Frederike

    2015-01-01

    Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In

  10. 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."

  11. Engineering Large Animal Species to Model Human Diseases.

    Science.gov (United States)

    Rogers, Christopher S

    2016-07-01

    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. Copyright © 2016 John Wiley & Sons, Inc.

  12. Alternative animal model for studies of total skin thickness burns.

    Science.gov (United States)

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-10-01

    To present an alternative experimental model of third degree burn of easy reproducibility. Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with exposure time of 10 seconds and group 15 (G15) the animals were burned at 150°C with exposure time of 15 seconds. Histopathological analyzes showed that all three groups had similar morphological characteristics, with total thickness involvement. The technique is effective to reproduce a third degree burn and suggests the temperature of 150ºC with 5 seconds of exposure in order to minimize the risks to the animals.

  13. Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease.

    Science.gov (United States)

    Chang, H-H; Chao, H-N; Walker, C S; Choong, S-Y; Phillips, A; Loomes, K M

    2015-11-01

    Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease. Copyright © 2015 the American Physiological Society.

  14. Animal models of chronic wound care: the application of biofilms in clinical research

    Directory of Open Access Journals (Sweden)

    Trøstrup H

    2016-11-01

    Full Text Available Hannah Trøstrup,1 Kim Thomsen,1 Henrik Calum,2 Niels Høiby,1,3 Claus Moser1 1Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, 3Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark Abstract: Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s, and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should

  15. New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.

    Science.gov (United States)

    Leonova, Elina; Sokolovska, Jelizaveta; Boucher, Jean-Luc; Isajevs, Sergejs; Rostoka, Evita; Baumane, Larisa; Sjakste, Tatjana; Sjakste, Nikolajs

    2016-07-01

    Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ-induced diabetes caused an increase in NO production in the liver, kidneys, blood and muscles, but a decrease in NO in adipose tissue of STZ-treated animals. Cerebrocrast treatment was followed by normalization of NO production in the liver, kidneys and blood. Two other DHPs, etaftorone and fenoftorone, were effective in decreasing NO production in kidneys, blood and muscles of diabetic animals. Furthermore, inhibitors of nitric oxide synthase (NOS) and an inhibitor of xanthine oxidoreductase (XOR) decreased NO production in kidneys of diabetic animals. Treatment with etaftorone decreased expression of inducible NOS and XOR in kidneys, whereas it increased the expression of endothelial NOS. In vitro, the studied DHPs did not significantly inhibit the activities of NOS and XOR but affected the reactivity of peroxynitrite with DNA. These new DHPs thus appear of strong interest for treatment of DM complications. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. Animal models of disc degeneration and major genetic strategies.

    Science.gov (United States)

    Sun, Fu; Qu, Ji-Ning; Zhang, Yin-Gang

    2013-01-01

    The establishment of a reliable animal model of lumbar disc degeneration (AMDD) is important for studying pathogenesis and evaluating treatment effectiveness. However, an ideal AMDD for use in laboratory studies has not yet been produced. This retrospective study reviews and compares several common AMDD and discusses their strengths and weaknesses. We also suggest a new method for establishing future AMDD. The identified genes associated with disc degeneration are susceptibility genes, which elevate risk but do not necessarily lead to disease occurrence. We propose to identify families with hereditary disc degeneration, find major casual genes with exome sequencing, and establish transgenic animal models. This approach may help us to build an improved AMDD.

  17. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

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

    Science.gov (United States)

    Tyutyunov, Yuri V.; Titova, Lyudmila I.

    2017-06-01

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

  19. Influence of uncontrolled diabetes mellitus on periodontal tissues during orthodontic tooth movement: a systematic review of animal studies

    Directory of Open Access Journals (Sweden)

    Shariq Najeeb

    2017-02-01

    Full Text Available Abstract Diabetes mellitus (DM may adversely affect periodontal tissues during orthodontic tooth movement (OTM. The aim of this review is to systematically analyze and review animal studies investigating the effect of DM on periodontal tissues during OTM. An electronic search was conducted via PubMed/Medline, Google Scholar, Embase, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials (CONTROL using the keywords “diabetes,” “orthodontics,” and “tooth movement” for studies published between January 2000 and August 2016. After elimination of duplicate items, the primary search resulted in 89 articles. After exclusion of irrelevant articles on the basis of abstract and title, full texts of 25 articles were read to exclude additional irrelevant studies. Seven animal studies were included in this review for qualitative analysis. When compared to healthy animals, more bone resorption and diminished bone remodeling were observed in diabetic animals in all studies. Furthermore, DM decreased the rate of OTM in one study, but in another study, DM accelerated OTM. DM may adversely affect bone remodeling and tooth movement during application of orthodontic forces. However, a number of potential sources of bias and deficiencies in methodology are present in studies investigating the association between OTM and DM. Hence, more long-term and well-designed studies are required before the exact mechanism and impact of DM on outcomes of orthodontic treatment is understood.

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

    Directory of Open Access Journals (Sweden)

    Arnoldo eSantos

    2015-10-01

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

  1. Contemporary Animal Models For Human Gene Therapy Applications.

    Science.gov (United States)

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

    2015-01-01

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

  2. 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.

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

    Science.gov (United States)

    Toyoda, Atsushi

    2017-07-01

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

  4. A systematic review of current osteoporotic metaphyseal fracture animal models.

    Science.gov (United States)

    Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

    2018-01-01

    The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. 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.

  7. Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Damir Hamamdzic

    2013-01-01

    Full Text Available Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9 gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

  8. 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. © 2016 AlphaMed Press.

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

    Science.gov (United States)

    Chujitarom, Wannaporn; Piriyasurawong, Pallop

    2017-01-01

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

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

    African Journals Online (AJOL)

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

  11. Unraveling the genetics of chronic kidney disease using animal models

    NARCIS (Netherlands)

    Korstanje, Ron; DiPetrillo, K.

    2004-01-01

    Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to

  12. In search for animal models of female sexual dysfunction

    NARCIS (Netherlands)

    Snoeren, E.M.S.

    2010-01-01

    Female Sexual Dysfunction (FSD) is a disorder that affects around 40% of the population. Low sexual arousal and low sexual desire are the most common problems. The mechanisms underlying the disorder are still unclear. The aims of this thesis were 1) the search for animal models of FSD, 2) the

  13. 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…

  14. Animal models for plaque rupture: a biomechanical assessment

    NARCIS (Netherlands)

    van der Heiden, Kim; Hoogendoorn, Ayla; Daemen, Mat J.; Gijsen, Frank J. H.

    2016-01-01

    Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque

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

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

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

    African Journals Online (AJOL)

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

  17. Modeling herbivorous animal digestive system as 3- continuous ...

    African Journals Online (AJOL)

    Modeling herbivorous animal digestive system as 3- continuous stirred tank reactor (CSTR) and 1-plug flow reactor (PFR) in series with specific reference to ... This shows the efficiency of each reactor at converting the purely lignocellulosics substrates to useful products like protein, vitamin, fatty acid and the bye-products.

  18. Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

    NARCIS (Netherlands)

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

    1993-01-01

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

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  20. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

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

    2011-01-01

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

  1. A review of animal models for portal vein embolization

    NARCIS (Netherlands)

    Huisman, Floor; van Lienden, Krijn P.; Damude, Samantha; Hoekstra, Lisette T.; van Gulik, Thomas M.

    2014-01-01

    Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. We performed a

  2. Animal models for arthritis: innovative tools for prevention and treatment

    NARCIS (Netherlands)

    Kollias, G.; Papadaki, P.; Apparailly, F.; Vervoordeldonk, M.J.; Holmdahl, R.; Baumans, V.; Desaintes, C.; Di Santo, J.; Distler, J.; Garside, P.; Hegen, M.; Huizinga, T.W.J.; Jüngel, A.; Klareskog, L.; McInnes, I.; Ragoussis, I.; Schett, G.; Hart, B.t.; Tak, P.P.; Toes, R.; van den Berg, W.; Wurst, W.; Gay, S.

    2011-01-01

    The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature

  3. 75 FR 54349 - Animal Models-Essential Elements To Address Efficacy Under the Animal Rule; Notice of Public...

    Science.gov (United States)

    2010-09-07

    ... the Animal Rule; Notice of Public Meeting; and Reopening of Comment Period AGENCY: Food and Drug... challenges as addressed in the draft document entitled ``Guidance for ] Industry: Animal Models--Essential Elements to Address Efficacy Under the Animal Rule'' dated January 2009 (Draft Guidance), and as related to...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

  5. 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. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. An animal model of spontaneous metabolic syndrome: Nile grass rat

    OpenAIRE

    Noda, Kousuke; Melhorn, Mark I.; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K. C.; Hafezi-Moghadam, Ali

    2010-01-01

    Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically e...

  7. Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

    Directory of Open Access Journals (Sweden)

    Yusuke Kemmochi

    2013-01-01

    Full Text Available Spontaneously Diabetic Torii Leprfa (SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

  8. Experimental animal model for late postradiation reaction of the colon

    International Nuclear Information System (INIS)

    Trott, K.R.

    1987-01-01

    Experimental animal model worked out in Muenchen is discussed in which late postradiation reaction in Wistar rats following local irradiation of the colon manifests itself by appearance of colonic stenoses causing death of the animal. Clinical symptoms of this reaction together with results of histopathologic examination of the excised parts of the colon localized in the irradiated area are discussed. The relationships effect-dose obtained in this system for X radiation applying different regimen of dose fractionation and different total times of irradiation are presented. 8 refs., 5 figs., 1 tab. (author)

  9. Alternative animal model for studies of total skin thickness burns

    OpenAIRE

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-01-01

    Abstract Purpose: To present an alternative experimental model of third degree burn of easy reproducibility. Methods: Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with e...

  10. 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.

  11. 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.

  12. Diabetes management and glycemic control in youth with type 1 diabetes: test of a predictive model

    Science.gov (United States)

    Ittenbach, Richard; Rohan, Jennifer M.; Gupta, Resmi; Pendley, Jennifer Shroff; Delamater, Alan

    2014-01-01

    The objective of this study was to test a comprehensive model of biologic (pubertal status), family (communication and conflict), and psychological influences (behavioral autonomy) on diabetes management and glycemic control in a sample of youth (N = 226) with type 1 diabetes recruited during late childhood/early adolescence (ages 9–11 years). The study design was a prospective, multisite, multi-method study involving prediction of diabetes management and glycemic control 1 year post-baseline. The primary outcome measures included diabetes management behaviors based on the Diabetes Self-Management Profile (DSMP) administered separately to mothers and youth and glycemic control measured by glycated hemoglobin (HbA1c) obtained by blood samples and analyzed by a central laboratory to ensure standardization. Our hypothesized predictive model received partial support based on structural equation modeling analyses. Family conflict predicted less adequate glycemic control 1 year later (p < 0.05). Higher conflict predicted less adequate diabetes management and less adequate glycemic control. More advanced pubertal status also predicted less adequate glycemic control, but behavioral autonomy did not. Family conflict is an important, potentially clinically significant influence on glycemic control that should be considered in primary and secondary prevention in the management of type 1 diabetes in youth. PMID:22569775

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

    2014-01-01

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

  15. Animal models for Ebola and Marburg virus infections

    Science.gov (United States)

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

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

  16. 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.

  17. An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

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    Roxana Ramírez-Sandoval

    2015-01-01

    Full Text Available Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO32. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

  18. Transmission of Helicobacter pyori in an animal model.

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    Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L

    2001-01-01

    An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.

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

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    Enderli TA

    2016-09-01

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

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

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

    2016-11-01

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

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

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    Roth, J A; Flaming, K P

    1990-01-01

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

  2. Infantile Spasms: A Critical Review of Emerging Animal Models

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    Stafstrom, Carl E

    2009-01-01

    Infantile spasms is a developmental epilepsy syndrome with unique clinical and EEG features, a specific pattern of pharmacological responsiveness, and poor outcome in terms of cognition and epilepsy. Despite the devastating nature of infantile spasms, little is known about its pathogenesis. Until recently, there has been no animal model available to investigate the pathophysiology of the syndrome or to generate and test novel therapies. Now, several promising animal models have emerged, spanning the etiological spectrum from genetic causes (e.g., Down syndrome or Aristaless-related homeobox [ARX] mutation) to acquired causes (e.g., endogenous and exogenous toxins or stress hormones with convulsant activity or blockade of neural activity). These new models are discussed in this review, with emphasis on the insights each can provide for understanding, treating, and preventing infantile spasms. PMID:19471616

  3. Reproduction of an animal model of landmine blast injuries

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    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

  4. Animal Modelling of Interstitial Cystitis/Bladder Pain Syndrome.

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    Birder, Lori; Andersson, Karl-Erik

    2018-01-01

    The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.

  5. Sleep and Obesity: A focus on animal models

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

    2012-01-01

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

  6. Tree shrew (Tupaia belangeri chinensis, a novel non-obese animal model of non-alcoholic fatty liver disease

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    Linqiang Zhang

    2016-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR and type 2 diabetes (T2D, for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4 corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis, which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD.

  7. Pharmacological Evaluation of Chrozophora tinctoria as Wound Healing Potential in Diabetic Rat’s Model

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    Harikesh Maurya

    2016-01-01

    Full Text Available Objective. The study was designed to evaluate pharmacological potential of hydroalcoholic leaves extract of Chrozophora tinctoria intended for wound healing in diabetic rats’ model. Methods. The method used to evaluate the pharmacological potential of hydroalcoholic leave extract was physical incision rat model. In this model, cutting of the skin and/or other tissues with a sharp blade has been made and the rapid disruption of tissue integrity with minimal collateral damage was observed shortly. Animals used in the study were divided into four groups that consist of six animals in each group. Group I serves as normal control, Group II serves as disease control, Group III was used as standard treatment (Povidone iodine 50 mg/kg b.w., and Group IV was used for test drug (C. tinctoria 50 mg/kg b.w.. Result. The hydroalcoholic leave extract of Chrozophora tinctoria has been significantly observed to heal the wound (98% in diabetic rats within 21 days, while standard drug (Povidone iodine healed the wound about 95% in the same condition. The oral dose (50 mg/kg b.w. of Chrozophora tinctoria was also found to improve the elevated blood glucose level in comparison to disease control group, which increased after the oral administration of Streptozotocin. Conclusion. The Chrozophora tinctoria has significant wound healing potential in the animal having physically damaged tissue in diabetic condition.

  8. Diet before and during Pregnancy and Offspring Health: The Importance of Animal Models and What Can Be Learned from Them

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    Pascale Chavatte-Palmer

    2016-06-01

    Full Text Available This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition plays a seminal role in determining the offspring’s long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD. In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta or physical (ovine maternal and lamb birth weight resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to

  9. Sex Differences in Animal Models: Focus on Addiction

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    Becker, Jill B.

    2016-01-01

    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

  10. p38 mediates mechanical allodynia in a mouse model of type 2 diabetes

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    Hong Yu

    2010-05-01

    Full Text Available Abstract Background Painful Diabetic Neuropathy (PDN affects more than 25% of patients with type 2 diabetes; however, the pathogenesis remains unclear due to lack of knowledge of the molecular mechanisms leading to PDN. In our current study, we use an animal model of type 2 diabetes in order to understand the roles of p38 in PDN. Previously, we have demonstrated that the C57BLK db/db (db/db mouse, a model of type 2 diabetes that carries the loss-of-function leptin receptor mutant, develops mechanical allodynia in the hind paws during the early stage (6-12 wk of age of diabetes. Using this timeline of PDN, we can investigate the signaling mechanisms underlying mechanical allodynia in the db/db mouse. Results We studied the role of p38 in lumbar dorsal root ganglia (LDRG during the development of mechanical allodynia in db/db mice. p38 phosphorylation was detected by immunoblots at the early stage of mechanical allodynia in LDRG of diabetic mice. Phosphorylated p38 (pp38 immunoreactivity was detected mostly in the small- to medium-sized LDRG neurons during the time period of mechanical allodynia. Treatment with an antibody against nerve growth factor (NGF significantly inhibited p38 phosphorylation in LDRG of diabetic mice. In addition, we detected higher levels of inflammatory mediators, including cyclooxygenase (COX 2, inducible nitric oxide synthases (iNOS, and tumor necrosis factor (TNF-α in LDRG neurons of db/db mice compared to non-diabetic db+ mice. Intrathecal delivery of SB203580, a p38 inhibitor, significantly inhibited the development of mechanical allodynia and the upregulation of COX2, iNOS and TNF-α. Conclusions Our findings suggest that NGF activated-p38 phosphorylation mediates mechanical allodynia in the db/db mouse by upregulation of multiple inflammatory mediators in LDRG.

  11. Neural models on temperature regulation for cold-stressed animals

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    Horowitz, J. M.

    1975-01-01

    The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.

  12. Influence of Overt Diabetes Mellitus on Cyclosporine Pharmacokinetics in a Canine Model

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    Khalid M. Alkharfy

    2009-01-01

    Full Text Available Background/Aims. Diabetic patients usually require more medications than their nondiabetic counterparts. This work examined the effect of hyperglycemia on the pharmacokinetic properties of cyclosporine in a diabetic dog model. Main Methods. Diabetes was induced using a streptozotocin/alloxan combination and verified by measuring the serum glucose level. Cyclosporine was administered as a bolus intravenous dose of 5 mg/kg, and blood samples were collected at different time points for determining drug concentrations and biochemical analyses. Results. Diabetic dogs showed a significant increase in total body clearance of cyclosporine compared to healthy controls (0.457 L hr−1Kg−1 versus 0.201 L hr−1Kg−1, =.0019 and a decrease in its biological half-life (9.32 hours versus 22.56 hours, =.0125. In addition, diabetic animals exhibited a higher total cholesterol (7.20±0.62 mmol/L and 5.28±0.36 mmol/L; <.05 as well as more serum low density lipoproteins (4.45±0.72 mmol/L versus 1.06±0.10 mmol/L; <.05. Conclusion. Overt diabetes alters cyclosporine disposition by modulating its clearance. Abnormalities in the lipid profile, among other factors, may contribute to the accelerated metabolic degradation of cyclosporine under hyperglycemic conditions.

  13. Large Animal Models for Foamy Virus Vector Gene Therapy

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    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.

  14. Behavioral impairments in animal models for zinc deficiency

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    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.

  15. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

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    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  16. Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study.

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    Sluijs, Ivonne; Beulens, Joline W J; van der A, Daphne L; Spijkerman, Annemieke M W; Grobbee, Diederick E; van der Schouw, Yvonne T

    2010-01-01

    Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk. A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records. During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77-2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80-2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk. Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

  17. Improvement of insulin secretion in rat models of diabetes after ACEI/ARB therapy

    International Nuclear Information System (INIS)

    Tian Jingyan; Li Fengying; Liu Yun; Long Hongmei; Li Weiyi; Wang Xiao; Zhang Hongli; Li Guo; Luo Min

    2009-01-01

    Objective To study the effect of ACEI/ARB therapy on the secretion of insulin and glucagon as well as serum lipid peroxidation marker 8-iso PGF-2α levels in streptozoticin (STZ) induced diabetic rat models.Methods Twenty-four rat models of STZ induced diabetes were prepared (random blood sugar>16.7 mmol/L). Of which, 8 models were fed enalaprial 5mg/kg/d, 8 models were fed losartan 10μg/kg/d and 8 models left unterated. Fasting serum insulin,glucagon (with RIA) and 8-iso PGF-2α (with ELISA) levels were measured in these models and 8 control rats three weeks later. Intravenous glucose tolerance test (IVGTT) were performed in 12 rats (3 animals in each group) six weeks later. Results: Serum levels of insulin in the treated models were higher than those in the non-treated models but without significance (P>0.05). Serum levels of glucagon and 8-iso PGF-2α levels in the treated models were significantly lower than those in the non-treated models (P 6 x ) in the treated models. Conclusion: ACEI/ARB treatment could improve the secretion of insulin in rat models of diabetes, which might be beneficial for controlling the progression of the disease. This phenomenon is consistent with the result of clinical study. (authors)

  18. Relevance of animal models to human tardive dyskinesia

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    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.

  19. Modelling gait transition in two-legged animals

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    Pinto, Carla M. A.; Santos, Alexandra P.

    2011-12-01

    The study of locomotor patterns has been a major research goal in the last decades. Understanding how intralimb and interlimb coordination works out so well in animals' locomotion is a hard and challenging task. Many models have been proposed to model animal's rhythms. These models have also been applied to the control of rhythmic movements of adaptive legged robots, namely biped, quadruped and other designs. In this paper we study gait transition in a central pattern generator (CPG) model for bipeds, the 4-cells model. This model is proposed by Golubitsky, Stewart, Buono and Collins and is studied further by Pinto and Golubitsky. We briefly resume the work done by Pinto and Golubitsky. We compute numerically gait transition in the 4-cells CPG model for bipeds. We use Morris-Lecar equations and Wilson-Cowan equations as the internal dynamics for each cell. We also consider two types of coupling between the cells: diffusive and synaptic. We obtain secondary gaits by bifurcation of primary gaits, by varying the coupling strengths. Nevertheless, some bifurcating branches could not be obtained, emphasizing the fact that despite analytically those bifurcations exist, finding them is a hard task and requires variation of other parameters of the equations. We note that the type of coupling did not influence the results.

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

    Science.gov (United States)

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

    2014-09-26

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

  1. Gender Differences in Animal Models of Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Hagit Cohen

    2011-01-01

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

  2. Altered glial plasticity in animal models for mood disorders.

    Science.gov (United States)

    Czéh, Boldizsár; Fuchs, Eberhard; Flügge, Gabriele

    2013-10-01

    Numerous clinical evidences support the notion that glial changes in fronto-limbic brain areas could contribute to the pathophysiology of mood disorders. Glial alterations have been reported not only in patients, but also in various kinds of animal models for depression. Molecular and cellular data suggest that all the major classes of glial cells are affected in these conditions, including astrocytes, oligodendrocytes, NG2-positive cells and microglia. The aim of this review was to summarize the currently available experimental results demonstrating alterations in glial morphology and functioning in animal models for mood disorders. Better understanding of these glial changes affecting neuronal activity could help us to identify novel targets for the development of antidepressant drugs.

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

    Science.gov (United States)

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

    2014-12-30

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

  4. Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

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    Matthias Edinger

    1999-10-01

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

  5. A novel animal model of dysphagia following stroke.

    Science.gov (United States)

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

    2014-02-01

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

  6. Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus: a novel model for diet-induced type 2 diabetes and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Maslova Ekaterina

    2010-04-01

    Full Text Available Abstract Background The prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2 diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases. Objective Within this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome. Methods Compiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity, food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease. Results The Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2 diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance, abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity in older male Nile rats in long term studies

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

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lavoie

    2012-01-01

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

  8. Stem cells in animal asthma models: a systematic review.

    Science.gov (United States)

    Srour, Nadim; Thébaud, Bernard

    2014-12-01

    Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  12. Multilevel model based glucose control for type-1 diabetes patients.

    Science.gov (United States)

    Garcia-Gabin, Winston; Jacobsen, Elling W

    2013-01-01

    Diabetes is a disease that involves alterations at multiple biological levels, ranging from intracellular signalling to organ processes. Since glucose homeostasis is the consequence of complex interactions that involve a number of factors, the control of diabetes should be based on a multilevel analysis. In this paper, a novel approach to design of closed-loop glucose controllers based on multilevel models is presented. A control scheme is proposed based on combining a pharmacokinetic/pharmacodynamic model with an insulin signal transduction model for type 1 diabetes mellitus patients. Based on this, an insulin feedback control schemes is designed. Two main advantages of explicitly utilizing information at the intracellular level were obtained. First, significant reduction of hypoglycaemic risk by reducing the undershoot in glucose levels in response to added insulin. Second, robust performance for inter-patient changes, demonstrated through application of the multilevel control strategy to a well established in silico population of diabetic patients.

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

    Science.gov (United States)

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

    2016-04-01

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

  14. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  15. 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.

  16. 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

    help but careful evaluation of the cellular mechanisms, safety and translational relevance of new procedures are required. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult...... hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g. PN, milk diets, long/short chain lipids, pre- and probiotics). Conversely......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....

  17. Cell therapy in dilated cardiomyopathy: from animal models to clinical trials

    Directory of Open Access Journals (Sweden)

    C. del Corsso

    2011-05-01

    Full Text Available Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases.

  18. Biochemical correlates in an animal model of depression

    International Nuclear Information System (INIS)

    Johnson, J.O.

    1986-01-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

  20. Basic mechanisms of catastrophic epilepsy – overview from animal models

    Science.gov (United States)

    Galanopoulou, Aristea S.

    2013-01-01

    Infantile spasms are age-specific seizures of infantile epileptic encephalopathies that are usually associated with poor epilepsy and neurodevelopmental outcomes. The current treatments are not always effective and may be associated with significant side effects. Various mechanisms have been proposed as pathogenic for infantile spasms, including cortical or brainstem dysfunction, disruption of normal cortical-subcortical communications, genetic defects, inflammation, stress, developmental abnormalities. Many of these have been recently tested experimentally, resulting into the emergence of several animal models of infantile spasms. The stress theory of spasms yielded the corticotropin releasing hormone (CRH) induced model, which showed the higher proconvulsant potency of CRH in developing rats, although only limbic seizures were observed. Models of acute induction of infantile spasms in rodents include the N-methyl-D-aspartate (NMDA) model of emprosthotonic seizures, the prenatal betamethasone and prenatal stress variants of the NMDA model, and the γ-butyrolactone induced spasms in a Down’s syndrome mouse model. Chronic rodent models of infantile spasms include the tetrodotoxin model and the multiple-hit models in rats, as well as two genetic mouse models of interneuronopathies with infantile spasms due to loss of function of the aristaless X-linked homeobox related gene (ARX). This review discusses the emerging mechanisms for generation of infantile spasms and their associated chronic epileptic and dyscognitive phenotype as well as the recent progress in identifying pathways to better treat this epileptic encephalopathy. PMID:23312951

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2009-12-07

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

  3. Large animal models and new therapies for glycogen storage disease.

    Science.gov (United States)

    Brooks, Elizabeth D; Koeberl, Dwight D

    2015-05-01

    Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders.

  4. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-01-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition. PMID:27321428

  5. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice.

    Science.gov (United States)

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-11-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

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

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    Ying Zhang

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

  7. Current understanding of hypospadias: relevance of animal models.

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    Cunha, Gerald R; Sinclair, Adriane; Risbridger, Gail; Hutson, John; Baskin, Laurence S

    2015-05-01

    Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.

  8. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

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    Nihar Ranjan Jana

    2012-01-01

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

  9. Understanding the Pathogenesis of Angelman Syndrome through Animal Models

    Science.gov (United States)

    Jana, Nihar Ranjan

    2012-01-01

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention. PMID:22830052

  10. Sodium salicylate reduced insulin resistance in the retina of a type 2 diabetic rat model.

    Science.gov (United States)

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J; Steinle, Jena J

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNFα and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNFα and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models.

  11. Sodium Salicylate Reduced Insulin Resistance in the Retina of a Type 2 Diabetic Rat Model

    Science.gov (United States)

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J.; Steinle, Jena J.

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNFα and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNFα and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models. PMID:25874611

  12. The German and Belgian accreditation models for diabetic foot services.

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    Morbach, Stephan; Kersken, Joachim; Lobmann, Ralf; Nobels, Frank; Doggen, Kris; Van Acker, Kristien

    2016-01-01

    The International Working Group on the Diabetic Foot recommends that auditing should be part of the organization of diabetic foot care, the efforts required for data collection and analysis being balanced by the expected benefits. In Germany legislature demands measures of quality management for in- and out-patient facilities, and, in 2003, the Germany Working Group on the Diabetic Foot defined and developed a certification procedure for diabetic foot centres to be recognized as 'specialized'. This includes a description of management facilities, treatment procedures and outcomes, as well as the organization of mutual auditing visits between the centres. Outcome data is collected at baseline and 6 months on 30 consecutive patients. By 2014 almost 24,000 cases had been collected and analysed. Since 2005 Belgian multidisciplinary diabetic foot clinics could apply for recognition by health authorities. For continued recognition diabetic foot clinics need to treat at least 52 patients with a new foot problem (Wagner 2 or more or active Charcot foot) per annum. Baseline and 6-month outcome data of these patients are included in an audit-feedback initiative. Although originally fully independent of each other, the common goal of these two initiatives is quality improvement of national diabetic foot care, and hence exchanges between systems has commenced. In future, the German and Belgian accreditation models might serve as templates for comparable initiatives in other countries. Just recently the International Working Group on the Diabetic Foot initiated a working group for further discussion of accreditation and auditing models (International Working Group on the Diabetic Foot AB(B)A Working Group). Copyright © 2016 John Wiley & Sons, Ltd.

  13. Tele-diabetology to Screen for Diabetes and Associated Complications in Rural India: The Chunampet Rural Diabetes Prevention Project Model.

    Science.gov (United States)

    Mohan, Viswanathan; Prathiba, Vijayaraghavan; Pradeepa, Rajendra

    2014-03-01

    Diabetes, with its acute and long-term complications, has become a major health hazard in developing countries. An estimated 62.4 million people in India have diabetes. With increasing urbanization and industrialization, we can expect huge numbers of people with diabetes in India in the future. Moreover, all diabetes efforts in India are currently focused in urban areas while 70% of India's population actually lives in rural areas. The current statistics demonstrates that urgent interventions are mandatory to curb the epidemic of diabetes and its complications at the grassroots level. This gap in providing diabetes care can be nullified by the use of tele-diabetology. This holds great potential to overcome barriers and improve quality and access to diabetes care to remote, underserved areas of developing counties. The Chunampet Rural Diabetes Prevention Project (CRDPP) has been developed and tested as a successful model for screening and delivering diabetes care to rural areas in developing countries. Using a tele-diabetology mobile van loaded with appropriate equipment, trained technicians, and satellite technology helped us to screen for diabetes and its complications and deliver diabetes care to remote villages in southern India. The Chunampet model can be applied in reaching out to remote areas where specialized diabetes care facilities may not be available. © 2014 Diabetes Technology Society.

  14. Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes.

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    Viorica Ionut

    Full Text Available Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes.We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines.After 10 weeks of high-fat diet (HFD, adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg. After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7 or placebo (n = 7 for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG, the oral glucose tolerance test (OGTT, insulinogenic index and the graded-hyperglycemic clamp (clamp insulinogenic index. Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro.OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5% (P = 0.011. IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9% (P = 0.002. AIRG decreased by 54.0% (IQR, 40.7% (P = 0.010, leading to mild fasting hyperglycemia (P = 0.039. Exenatide, compared with placebo, decreased body weight (P<0.001 without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040 and clamp-based insulinogenic indexes (P = 0.016, improved insulin secretion in vitro (P = 0.041, but had no noticeable effect on insulin sensitivity (P = 0.405.In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes.

  15. Using Computational and Mechanical Models to Study Animal Locomotion

    Science.gov (United States)

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

    2012-01-01

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

  16. Prebiotic effect of Agave fourcroydes fructans: an animal model.

    Science.gov (United States)

    García-Curbelo, Yanelys; Bocourt, Ramón; Savón, Lourdes L; García-Vieyra, Maria Isabel; López, Mercedes G

    2015-09-01

    The use of prebiotics such as fructans has increased in human and animal nutrition because of their productive performance and health benefits. Agave fourcroydes has shown high concentrations of fructans in their stems; however, there is no information on new products derived from this plant that might enhance its added value. Therefore, we evaluated the prebiotic effect of Agave fourcroydes fructans in an animal model. Male mice (C57BL/6J) were fed on parallel form with a standard diet or diets supplemented with 10% of fructans from Cichorium intybus (Raftilose P95) and Agave fourcroydes from Cuba for 35 days. The body weight, food intake, blood glucose, triglycerides and cholesterol, gastrointestinal organ weights, fermentation indicators in cecal and colon contents and mineral content in femurs were determined. The body weight and food intake of mice were not significantly modified by any treatment. However, serum glucose, cholesterol and triglycerides decreased (P Agave fourcroydes in the mice diet induced a prebiotic response, similar to or greater than the commercial product (Raftilose P95) and this constitutes a promising alternative with potential use not only in animal but also in human diets.

  17. Using computational and mechanical models to study animal locomotion.

    Science.gov (United States)

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

    2012-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Hananeh Wael M.

    2015-09-01

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

  19. Animal model for endoscopic neurosurgical training: technical note.

    Science.gov (United States)

    Fernandez-Miranda, J C; Barges-Coll, J; Prevedello, D M; Engh, J; Snyderman, C; Carrau, R; Gardner, P A; Kassam, A B

    2010-10-01

    The learning curve for endonasal endoscopic and neuroendoscopic port surgery is long and often associated with an increase in complication rates as surgeons gain experience. We present an animal model for laboratory training aiming to encourage the young generation of neurosurgeons to pursue proficiency in endoscopic neurosurgical techniques. 20 Wistar rats were used as models. The animals were introduced into a physical trainer with multiple ports to carry out fully endoscopic microsurgical procedures. The vertical and horizontal dimensions of the paired ports (simulated nostrils) were: 35×20 mm, 35×15 mm, 25×15 mm, and 25×10 mm. 2 additional single 11.5 mm endoscopic ports were added. Surgical depth varied as desired between 8 and 15 cm. The cervical and abdominal regions were the focus of the endoscopic microsurgical exercises. The different endoscopic neurosurgical techniques were effectively trained at the millimetric dimension. Levels of progressive surgical difficulty depending upon the endoneurosurgical skills set needed for a particular surgical exercise were distinguished. LEVEL 1 is soft-tissue microdissection (exposure of cervical muscular plane and retroperitoneal space); LEVEL 2 is soft-tissue-vascular and vascular-capsule microdissection (aorto-cava exposure, carotid sheath opening, external jugular vein isolation); LEVEL 3 is artery-nerve microdissection (carotid-vagal separation); LEVEL 4 is artery-vein microdissection (aorto-cava separation); LEVEL 5 is vascular repair and microsuturing (aortic rupture), which verified the lack of current proper instrumentation. The animal training model presented here has the potential to shorten the length of the learning curve in endonasal endoscopic and neuroendoscopic port surgery and reduce the incidence of training-related surgical complications. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Utility of Small Animal Models of Developmental Programming.

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    Reynolds, Clare M; Vickers, Mark H

    2018-01-01

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

  1. Thymoma related myasthenia gravis in humans and potential animal models.

    Science.gov (United States)

    Marx, Alexander; Porubsky, Stefan; Belharazem, Djeda; Saruhan-Direskeneli, Güher; Schalke, Berthold; Ströbel, Philipp; Weis, Cleo-Aron

    2015-08-01

    Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) subtypes. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Comparative occurrence of diabetes in canine, feline, and few wild animals and their association with pancreatic diseases and ketoacidosis with therapeutic approach

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    Kamal Niaz

    2018-04-01

    Full Text Available Diabetes mellitus (DM is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated. Bibliographic search for the present review was done using PubMed, Scopus, and Google Scholar for articles on concurrent DM in small and wild animals. Persistent corpus luteal and pseudopregnancy in female dogs generate gestational DM (GDM. GDM can also be caused by extensive use of drugs/hormones such as glucocorticosteroids. Although many similarities are present between diabetic cats and diabetic humans which present islet amyloidosis, there was a progressive loss of β- and α-cells and the normal number of δ-cells. The most prominent similarity is the occurrence of islet amyloidosis in all cases of diabetic cat and over 90% of human non-insulin dependent DM Type-2. Acute pancreatic necrosis (APN occurs due to predisposing factors such as insulin antagonism, insulin resistance, alteration in glucose tolerance, obesity, hyperadrenocorticism, and persistent usage of glucocorticoids, as these play a vital role in the progression of APN. To manage such conditions, it is important to deal with the etiological agent, risk factors, diagnosis of diabetes, and hormonal and drug interaction along with its termination with suitable therapy (herbal protocols. It should be noted that the protocols used for the diagnosis and treatment of human DM are not appropriate for animals. Further investigations regarding diabetic conditions of pets and wild animals are required, which will benefit the

  3. Validity and Variability of Animal Models Used in Dentistry

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    Mohammad Ali Saghiri

    2015-01-01

    Full Text Available Background: Animal models have contributed to dental literature for several decades. The major aim of this review was to outline tooth development stages in mice, and attempt to addressing potential strain differences. A literature review was performed using electronic and hand-searching methods for the animal models in dentistry with special emphasis on mice and dentistry. Root canal development in both C57BL/6 and BALB/c strains were investigated. There are a number of published reports regarding the morphogenesis and molecular reaction and maturation stages of mice molars. We observed some similarity between the mice and human odontegeneis as primary factor for tooth development. Although mice may present some technical challenges, including the small size of the mouse molars, they have similar stages as humans for molar development, and can be used to monitor the effects of various biomaterials, regeneration, and remodeling. Thus, mice provide an ideal alternative model to study developmental and regenerative processes in dentistry.

  4. Steroid-associated osteonecrosis animal model in rats

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    Li-Zhen Zheng

    2018-04-01

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

  5. A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and Atherosclerosis.

    Science.gov (United States)

    Bornfeldt, Karin E; Kramer, Farah; Batorsky, Anna; Choi, Jinkuk; Hudkins, Kelly L; Tontonoz, Peter; Alpers, Charles E; Kanter, Jenny E

    2018-02-01

    Diabetic kidney disease and atherosclerotic disease are major causes of morbidity and mortality associated with type 2 diabetes (T2D), and diabetic kidney disease is a major cardiovascular risk factor. The black and tan, brachyury (BTBR) mouse strain with leptin deficiency (Lep ob ) has emerged as one of the best models of human diabetic kidney disease. However, no T2D mouse model of combined diabetic kidney disease and atherosclerosis exists. Our goal was to generate such a model. To this end, the low-density lipoprotein (LDL) receptor was targeted for degradation via inducible degrader of the LDL receptor (IDOL) overexpression, using liver-targeted adenoassociated virus serotype DJ/8 (AAV-DJ/8) in BTBR wild-type and BTBR Lep ob mice. Liver-targeted IDOL-AAV-DJ/8 increased plasma LDL cholesterol compared with the control enhanced green fluorescent protein AAV-DJ/8. IDOL-induced dyslipidemia caused formation of atherosclerotic lesions of an intermediate stage, which contained both macrophages and smooth muscle cells. BTBR Lep ob mice exhibited diabetic kidney disease. IDOL-induced dyslipidemia worsened albuminuria and glomerular macrophage accumulation but had no effect on mesangial expansion or podocyte numbers. Thus, by inducing hepatic degradation of the LDL receptor, we generated a T2D model of combined kidney disease and atherosclerosis. This model provides a new tool to study mechanisms, interactions, and treatment strategies of kidney disease and atherosclerosis in T2D. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

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    Fikse Freddy

    2009-09-01

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

  7. Cellular models for beta-cell function and diabetes gene therapy.

    Science.gov (United States)

    Green, A D; Vasu, S; Flatt, P R

    2018-03-01

    Diabetes is characterized by the destruction and/or relative dysfunction of insulin-secreting beta-cells in the pancreatic islets of Langerhans. Consequently, considerable effort has been made to understand the physiological processes governing insulin production and secretion in these cells and to elucidate the mechanisms involved in their deterioration in the pathogenesis of diabetes. To date, considerable research has exploited clonal beta-cell lines derived from rodent insulinomas. Such cell lines have proven to be a great asset in diabetes research, in vitro drug testing, and studies of beta-cell physiology and provide a sustainable, and in many cases, more practical alternative to the use of animals or primary tissue. However, selection of the most appropriate rodent beta cell line is often challenging and no single cell line entirely recapitulates the properties of human beta-cells. The generation of stable human beta-cell lines would provide a much more suitable model for studies of human beta-cell physiology and pathology and could potentially be used as a readily available source of implantable insulin-releasing tissue for cell-based therapies of diabetes. In this review, we discuss the history, development, functional characteristics and use of available clonal rodent beta-cell lines, as well as reflecting on recent advances in the generation of human-derived beta-cell lines, their use in research studies and their potential for cell therapy of diabetes. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  8. Comparative performance of diabetes-specific and general population-based cardiovascular risk assessment models in people with diabetes mellitus.

    Science.gov (United States)

    Echouffo-Tcheugui, J-B; Kengne, A P

    2013-10-01

    Multivariable models for estimating cardiovascular disease (CVD) risk in people with diabetes comprise general population-based models and those from diabetic cohorts. Whether one set of models should receive preference is unclear. We evaluated the evidence on direct comparisons of the performance of general population vs diabetes-specific CVD risk models in people with diabetes. MEDLINE and EMBASE databases were searched up to March 2013. Two reviewers independently identified studies that compared the performance of general CVD models vs diabetes-specific ones in the same group of people with diabetes. Independent, dual data extraction on study design, risk models, outcomes; and measures of performance was conducted. Eleven articles reporting on 22 pair wise comparisons of a diabetes-specific model (UKPDS, ADVANCE and DCS risk models) to a general population model (three variants of the Framingham model, Prospective Cardiovascular Münster [PROCAM] score, CardioRisk Manager [CRM], Joint British Societies Coronary Risk Chart [JBSRC], Progetto Cuore algorithm and the CHD-Riskard algorithm) were eligible. Absolute differences in C-statistic of diabetes-specific vs general population-based models varied from -0.13 to 0.09. Comparisons for other performance measures were unusual. Outcomes definitions were congruent with those applied during model development. In 14 comparisons, the UKPDS, ADVANCE or DCS diabetes-specific models were superior to the general population CVD risk models. Authors reported better C-statistic for models they developed. The limited existing evidence suggests a possible discriminatory advantage of diabetes-specific over general population-based models for CVD risk stratification in diabetes. More robust head-to-head comparisons are needed to confirm this trend and strengthen recommendations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Diabetes management at school: application of the healthy learner model.

    Science.gov (United States)

    Bobo, Nichole; Kaup, Tara; McCarty, Patricia; Carlson, Jessie Parker

    2011-06-01

    Every child with diabetes deserves a school nurse with the capacity to effectively manage the disease at school. The school nurse needs knowledge and skills to confidently provide care and communicate with health care providers and families. The Healthy Learner Model for Chronic Condition Management provided a framework to eliminate the disjointed approach to diabetes management at school, replacing it with a consistent, evidence-based approach. A diabetes resource nurse was a key component, providing support for the school nurse and collaboration between the school, community, family, and health care providers. Funded by a cooperative agreement from the Centers for Disease Control and Prevention (CDC), the National Association of School Nurses (NASN) chose five sites from across the country to implement this program-a project titled Managing and Preventing Diabetes and Weight Gain (MAP). This article describes the experience of two sites.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2016-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-15

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

  13. Tissue and Animal Models of Sudden Cardiac Death

    Science.gov (United States)

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; 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 expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

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

    Czech Academy of Sciences Publication Activity Database

    Svojanovská, Markéta; Stuchlík, Aleš

    2015-01-01

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

  15. The efficacy of Prosopis glandulosa as antidiabetic treatment in rat models of diabetes and insulin resistance.

    Science.gov (United States)

    George, C; Lochner, A; Huisamen, B

    2011-09-01

    Diabetes mellitus is rampantly increasing and the need for therapeutics is crucial. In recognition of this, untested antidiabetic agents are flooding the market. Diavite™ which is a product consisting solely of the dried and ground pods of Prosopis glandulosa (Torr.) [Fabaceae] is currently marketed as a food supplement with glucose stabilizing properties. However, these are anecdotal claims lacking scientific evidence. The aim of this study was to determine the efficacy of Prosopis glandulosa as an antidiabetic agent. Male Wistar rats were rendered (a) type 1 diabetic after an intraperitoneal injection of STZ (40 mg/kg) and (b) insulin resistant after a 16-week high caloric diet (DIO). Zucker fa/fa ZDF rats were used in a pilot study. Half of each group of animals was placed on Prosopis glandulosa treatment (100mg/kg/day) for 8 weeks and the remaining animals served as age-matched controls. At the time of sacrifice, blood was collected for glucose and insulin level determination, the pancreata of the STZ rats were harvested for histological analysis and cardiomyocytes prepared from the DIO and Zucker fa/fa hearts for determination of insulin sensitivity. Type 1 diabetic model: Prosopis glandulosa treatment resulted in significant increased insulin levels (pProsopis glandulosa treatment resulted in increased small β-cells (pProsopis glandulosa treatment partially preventing this. Zucker fa/fa rats: Prosopis glandulosa treatment significantly reduced fasting glucose levels (pProsopis glandulosa treatment resulted in an increased basal (pProsopis glandulosa treatment moderately lowers glucose levels in different animal models of diabetes, stimulates insulin secretion, leads to the formation of small β-cells and improves insulin sensitivity of isolated cardiomyocytes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Old and new synthetic cannabinoids: lessons from animal models.

    Science.gov (United States)

    Zanda, Mary Tresa; Fattore, Liana

    2018-02-01

    Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as 'marijuana-like' products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences. Animal models of drug addiction are frequently used in preclinical research to assess the abuse potential of new compounds, evaluate drug positive reinforcing effects and analyze drug-induced behaviors. Some of these protocols have been used recently to study the newly synthesized cannabinoid agonists and have started elucidating their pharmacology and actions in the brain. The aim of this review is to summarize the major findings reported by animal studies that tested synthetic cannabinoids of first, second, and third generation by using self-administration and reinstatement models, drug discrimination and conditioned place preference procedures. Altogether, behavioral studies clearly indicate that synthetic cannabinoids possess abuse liability, are likely to activate the brain reward circuit and induce positive subjective and reinforcing effects.

  17. Cytokine networks in animal models of colitis-associated cancer.

    Science.gov (United States)

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

    2015-01-01

    It is well-known that inflammatory bowel disease (IBD) poses an increased, yet not definitely estimated, risk of colitis-associated colon cancer (CAC), which is considered a more aggressive and distinct in both genetic and molecular levels clinical entity compared to sporadic colorectal cancer (CRC). The present review discusses the cytokine networks involved in CAC-based translational findings from suitable animal models of the disease. Moreover, we summarize the most prominent data concerning the role of Th1, Th2, Th17 and anti-inflammatory cytokines in the pathogenesis of CAC. Last, we briefly address the controversies between basic science findings in IBD and CAC and suggest further directions regarding research on cytokines. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of cytokines in the context of CAC. The MEDLINE database was thoroughly searched using the keywords: cytokines, colitis-associated cancer, animal models, carcinogenesis. Additional articles were gathered and evaluated. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Experimental animal data and modeling of late somatic effects

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1988-01-01

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

  19. Minimally invasive resynchronization pacemaker: a pediatric animal model.

    Science.gov (United States)

    Jordan, Christopher P; Wu, Kyle; Costello, John P; Ishibashi, Nobuyuki; Krieger, Axel; Kane, Timothy D; Kim, Peter; Berul, Charles I

    2013-12-01

    We developed a minimally invasive epicardial pacemaker implantation method for infants and congenital heart disease patients for whom a transvenous approach is contraindicated. The piglet is an ideal model for technical development. In 5 piglets we introduced a needle through subxiphoid approach under thoracoscopic guidance, inserting a wire into the pericardial space. Pacing leads were affixed to the left ventricular free wall and left atrial appendage. After verifying functionality with atrial and ventricular pacing and sensing, animals were euthanized. Pacemaker monitoring occurred daily for 4 days in the fifth animal. Through minimally invasive pericardial access, we directly visualized and fixated pacing leads to the left ventricle and left atrial appendage, successfully pacing atrium and ventricle. Epicardial structures were visualized. One piglet had contralateral pneumothorax, which resolved with needle decompression. No other adverse events occurred. Minimally invasive epicardial pacemaker implantation in an infant model is feasible and effective. This innovation may be of value for pacing and resynchronization in infants and congenital heart disease patients. Survival studies with permanent generator implantation are under way. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Ocular Manifestations of Alzheimer’s Disease in Animal Models

    Directory of Open Access Journals (Sweden)

    Miles Parnell

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia, and the pathological changes of senile plaques (SPs and neurofibrillary tangles (NFTs in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP presenilin (PS and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models.

  1. Experimental animal data and modeling of late somatic effects

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1988-01-01

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

  2. Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Francesca Sciandra

    2015-01-01

    Full Text Available In skeletal muscle, dystroglycan (DG is the central component of the dystrophin-glycoprotein complex (DGC, a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1 have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.

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

    Science.gov (United States)

    Ahmari, Susanne E.; Dougherty, Darin D.

    2015-01-01

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

  4. An intermediate animal model of spinal cord stimulation

    Directory of Open Access Journals (Sweden)

    Thomas Guiho

    2016-06-01

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

  5. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

    Science.gov (United States)

    Mi, Xue-Song; Yuan, Ti-Fei; Ding, Yong; Zhong, Jing-Xiang; So, Kwok-Fai

    2014-01-01

    Diabetic retinopathy (DR) is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. PMID:25429204

  6. Behavior of lyophilized biological valves in a chronic animal model.

    Science.gov (United States)

    Maizato, Marina J S; Taniguchi, Fabio P; Ambar, Rafael F; Pitombo, Ronaldo N M; Leirner, Adolfo A; Cestari, Idágene A; Stolf, Noedir A G

    2013-11-01

    Glutaraldehyde is used in order to improve the mechanical and immunogenic properties of biological tissues, such as bovine pericardium membranes, used to manufacture heart valve bioprostheses. Lyophilization, also known as freeze-drying, preserves biological material without damage by freezing the water content and removing ice by sublimation. Through this process, dehydrated products of high quality may be obtained; also, the material may be easily handled. The lyophilization process reduces aldehyde residues in biological tissue previously treated with glutaraldehyde, thus promoting reduction of cytotoxicity, increasing resistance to inflammation, and possibly decreasing the potential for tissue calcification. The objective of this study was to chronically evaluate the calcification of bovine pericardium heart valve prostheses, previously lyophilized or not, in an animal model. Six-month-old sheep received implants of lyophilized and unlyophilized heart valve prostheses in the pulmonary position with right bypass. The study followed 16 animals for a period of 90 days. Right ventricle-pulmonary artery (RV/PA) transvalvular pressure gradient was evaluated before and immediately after implantation and before explantation, as were tissue calcium, inflammation intensity, and thrombosis and pannus formation. The t-test was used for statistical analysis. Twelve animals survived to the end of the experiment, but one of the animals in the control group had endocarditis and was excluded from the data. Four animals died early. The mean RV/PA gradient on implantation was 2.0 ± 1.6 mm Hg in the control group and 6.2 ± 4.1 mm Hg in the lyophilized group (P = 0.064). This mean gradient increased at explantation to 7.7 ± 3.9 mm Hg and 8.6 ± 5.8 mm Hg, respectively (P = 0.777). The average calcium content in the tissue leaflets after 3 months was 21.6 ± 39.1 mg Ca(2+)/g dry weight in the control group, compared with an average content of 41.2 ± 46.9 mg Ca(2+)/g dry weight

  7. Toxin-Induced and Genetic Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs, but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.

  8. Nicotine addiction: studies about vulnerability, epigenesis and animal models

    Directory of Open Access Journals (Sweden)

    Bernabeu, Ramon

    2013-07-01

    Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse

  9. Learning from Animal Models of Obsessive-Compulsive Disorder

    Science.gov (United States)

    Monteiro, Patricia; Feng, Guoping

    2015-01-01

    Obsessive-Compulsive Disorder (OCD) affects 2–3% of the worldwide population and can cause significant distress and disability to its sufferers. Substantial challenges remain in the field of OCD research and therapeutics. Approved interventions only partially alleviate symptoms, with 30–40% of patients being resistant to treatment. Research evidence points towards the involvement of cortico-striato-thalamocortical circuitry (CSTC) although OCD’s etiology is still unknown. This review will focus on the most recent behavior, genetics and neurophysiological findings from animal models of OCD. Based on evidence from these models and parallels with human studies, we discuss the circuit hyperactivity hypothesis for OCD, a potential circuitry dysfunction of action termination, and the involvement of candidate genes. Adding a more biologically-valid framework to OCD will help us define and test new hypotheses and facilitate the development of targeted therapies based on disease-specific mechanisms. PMID:26037910

  10. Comparison of predictive models for the early diagnosis of diabetes

    NARCIS (Netherlands)

    M. Jahani (Meysam); M. Mahdavi (Mahdi)

    2016-01-01

    textabstractObjectives: This study develops neural network models to improve the prediction of diabetes using clinical and lifestyle characteristics. Prediction models were developed using a combination of approaches and concepts. Methods: We used memetic algorithms to update weights and to improve

  11. Ethyl acetate fraction of Aframomum melegueta fruit ameliorates pancreatic β-cell dysfunction and major diabetes-related parameters in a type 2 diabetes model of rats.

    Science.gov (United States)

    Mohammed, Aminu; Koorbanally, Neil Anthony; Islam, Md Shahidul

    2015-12-04

    In West Africa, various preparations of the fruit, seed and leaf of Aframomum melegueta K. Schum. are reputably used for the management of diabetes mellitus (DM) and other metabolic disorders. The present study evaluated the anti-diabetic effects of A. melegueta ethyl acetate fraction (AMEF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the AMEF once daily for four weeks. At the end of the intervention, diabetic untreated animals showed significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, pancreatic β-cell function (HOMA- β) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and β-cells. These alterations were reverted to near-normal after the treatment of AMEF at 150 and 300 mg/kg bw when, the effects were more pronounced at 300 mg/kg bw compared to the 150 mg/kg bw. The results of our study suggest that AMEF treatment at 300 mg/kg bw showed potent anti-diabetic effect in a T2D model of rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

    Directory of Open Access Journals (Sweden)

    Brendan K. Podell

    2017-02-01

    Full Text Available Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species.

  13. Fenugreek Prevents the Development of STZ-Induced Diabetic Nephropathy in a Rat Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Yingli Jin

    2014-01-01

    evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-β1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model.

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

    Science.gov (United States)

    Cai, Bin; Wang, Ning

    2016-01-01

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

  15. Gastroprotective activity of Zanthoxylum rhoifolium Lam. in animal models.

    Science.gov (United States)

    Freitas, F F B P; Fernandes, H B; Piauilino, C A; Pereira, S S; Carvalho, K I M; Chaves, M H; Soares, P M G; Miura, L M C V; Leite, J R S A; Oliveira, R C M; Oliveira, F A

    2011-09-01

    The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg

  16. A multifocal electroretinogram model predicting the development of diabetic retinopathy.

    Science.gov (United States)

    Bearse, Marcus A; Adams, Anthony J; Han, Ying; Schneck, Marilyn E; Ng, Jason; Bronson-Castain, Kevin; Barez, Shirin

    2006-09-01

    The prevalence of diabetes has been accelerating at an alarming rate in the last decade; some describe it as an epidemic. Diabetic eye complications are the leading cause of blindness in adults aged 25-74 in the United States. Early diagnosis and development of effective preventatives and treatments of diabetic retinopathy are essential to save sight. We describe efforts to establish functional indicators of retinal health and predictors of diabetic retinopathy. These indicators and predictors will be needed as markers of the efficacy of new therapies. Clinical trials aimed at either prevention or early treatments will rely heavily on the discovery of sensitive methods to identify patients and retinal locations at risk, as well as to evaluate treatment effects. We report on recent success in revealing local functional changes of the retina with the multifocal electroretinogram (mfERG). This objective measure allows the simultaneous recording of responses from over 100 small retinal patches across the central 45 degrees field. We describe the sensitivity of mfERG implicit time measurement for revealing functional alterations of the retina in diabetes, the local correspondence between functional (mfERG) and structural (vascular) abnormalities in eyes with early nonproliferative retinopathy, and longitudinal studies to formulate models to predict the retinal sites of future retinopathic signs. A multivariate model including mfERG implicit time delays and 'person' risk factors achieved 86% sensitivity and 84% specificity for prediction of new retinopathy development over one year at specific locations in eyes with some retinopathy at baseline. A preliminary test of the model yielded very positive results. This model appears to be the first to predict, quantitatively, the retinal locations of new nonproliferative diabetic retinopathy development over a one-year period. In a separate study, the predictive power of a model was assessed over one- and two-year follow

  17. A Canola Oil-Supplemented Diet Prevents Type I Diabetes-Caused Lipotoxicity and Renal Dysfunction in a Rat Model.

    Science.gov (United States)

    Cano-Europa, Edgar; Ortiz-Butron, Rocio; Camargo, Estela Melendez; Esteves-Carmona, María Miriam; Oliart-Ros, Rosa Maria; Blas-Valdivia, Vanessa; Franco-Colin, Margarita

    2016-11-01

    We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated. The mesenteric, retroperitoneal, and epididymal fat pads were dissected and weighed. The kidneys were used for lipid peroxidation (LP) and reactive oxygen species (ROS) quantifications. Diabetic rats fed with a canola oil-supplemented diet had higher body weights, were less hyperphagic, and their mesenteric, retroperitoneal, and epididymal fat pads weighed more than diabetic rats on an unsupplemented diet. The canola oil-supplemented diet decreased plasmatic concentrations of free fatty acids, triglycerides, and cholesterol; showed improved osmolarity, water clearances, and creatinine depuration; and had decreased LP and ROS. A canola oil-supplemented diet decreases hyperphagia and prevents lipotoxicity and renal dysfunction in a type I diabetes mellitus model.

  18. Is it acceptable to use animals to model obese humans?

    DEFF Research Database (Denmark)

    Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.

    2014-01-01

    for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal......Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments...... of animals in obesity research as especially problematic....

  19. Animal models for radiation injury, protection and therapy.

    Science.gov (United States)

    Augustine, Alison Deckhut; Gondré-Lewis, Timothy; McBride, William; Miller, Lara; Pellmar, Terry C; Rockwell, Sara

    2005-07-01

    Current events throughout the world underscore the growing threat of different forms of terrorism, including radiological or nuclear attack. Pharmaceutical products and other approaches are needed to protect the civilian population from radiation and to treat those with radiation-induced injuries. In the event of an attack, radiation exposures will be heterogeneous in terms of both dose and quality, depending on the type of device used and each victim's location relative to the radiation source. Therefore, methods are needed to protect against and treat a wide range of early and slowly developing radiation-induced injuries. Equally important is the development of rapid and accurate biodosimetry methods for estimating radiation doses to individuals and guiding clinical treatment decisions. Acute effects of high-dose radiation include hematopoietic cell loss, immune suppression, mucosal damage (gastrointestinal and oral), and potential injury to other sites such as the lung, kidney and central nervous system (CNS). Long-term effects, as a result of both high- and low-dose radiation, include dysfunction or fibrosis in a wide range of organs and tissues and cancer. The availability of appropriate types of animal models, as well as adequate numbers of animals, is likely to be a major bottleneck in the development of new or improved radioprotectors, mitigators and therapeutic agents to prevent or treat radiation injuries and of biodosimetry methods to measure radiation doses to individuals.

  20. Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Mi Young Lee

    2011-04-01

    Full Text Available BackgroundWhile there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.MethodsThirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5, spironolactone-treated (n=10, losartan-treated (n=9, and combination of spironolactone- and losartan-treated (n=9.ResultsAt week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.ConclusionThese results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

  1. Animal Models for Studying Triazole Resistance in Aspergillus fumigatus.

    Science.gov (United States)

    Lewis, Russell E; Verweij, Paul E

    2017-08-15

    Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Nevertheless, these models provide important insights that help guide treatment decisions in patients with triazole-resistant invasive aspergillosis. Animal models confirmed that a high triazole minimal inhibitory concentration corresponded with triazole treatment failure and that the efficacy of other classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triazole resistance mutations. Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis were explored as strategies to overcome resistance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Li X

    2017-01-01

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

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

    Science.gov (United States)

    Ohlemiller, Kevin K

    2009-06-24

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

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

    Science.gov (United States)

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

    2015-09-02

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

  5. Menu variations for diabetes mellitus patients using Goal Programming model

    Science.gov (United States)

    Dhoruri, Atmini; Lestari, Dwi; Ratnasari, Eminugroho

    2017-08-01

    Diabetes mellitus (DM) was a chronic metabolic disease characterized by higher than normal blood glucose level (normal blood glucose level = = 80 -120 mg/dl). In this study, type 2 DM which mostly caused by unhealthy eating habits would be investigated. Related to eating habit, DM patients needed dietary menu planning with an extracare regarding their nutrients intake (energy, protein, fat and carbohydrate). Therefore, the measures taken were by organizing nutritious dietary menu for diabetes mellitus patients. Dietary menu with appropriate amount of nutrients was organized by considering the amount of calories, proteins, fats and carbohydrates. In this study, Goal Programming model was employed to determine optimal dietary menu variations for diabetes mellitus patients by paying attention to optimal expenses. According to the data obtained from hospitals in Yogyakarta, optimal menu variations would be analyzed by using Goal Programming model and would be completed by using LINGO computer program.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

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

  8. Two new animal models for actinide toxicity studies

    International Nuclear Information System (INIS)

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

    1979-01-01

    Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies

  9. A large animal model for boron neutron capture therapy

    International Nuclear Information System (INIS)

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

    1992-01-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  12. Tissue mechanics, animal models, and pelvic organ prolapse: a review.

    Science.gov (United States)

    Abramowitch, Steven D; Feola, Andrew; Jallah, Zegbeh; Moalli, Pamela A

    2009-05-01

    Pelvic floor disorders such as pelvic organ prolapse, urinary incontinence, and fecal incontinence affect a large number of women each year. The pelvic floor can be thought of as a biomechanical structure due to the complex interaction between the vagina and its supportive structures that are designed to withstand the downward descent of the pelvic organs in response to increases in abdominal pressure. Although previous work has highlighted the biochemical changes that are associated with specific risk factors (i.e. parity, menopause, and genetics), little work has been done to understand the biomechanical changes that occur within the vagina and its supportive structures to prevent the onset of these pelvic floor disorders. Human studies are often limited due to the challenges of obtaining large tissue samples and ethical concerns. Therefore, it is necessary to investigate the use of animal models and their importance in understanding how different risk factors affect the biomechanical properties of the vagina and its supportive structures. In this review paper, we will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep. The anatomy and preliminary biomechanical findings are discussed along with the importance of considering experimental conditions, tissue anisotropy, and viscoelasticity when characterizing the biomechanical properties of vaginal tissue. Although there is not a lot of biomechanics research related to the vagina and pelvic floor, the future is exciting due to the significant potential for scientific findings that will improve our understanding of these conditions and hopefully lead to improvements in the prevention and treatment of pelvic disorders.

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

    Science.gov (United States)

    2017-10-01

    2) and in animal models of human autoimmune diseases including autoimmune colitis (3), experimental autoimmune encephalomyelitis (4), collagen...studied in multiple pre-clinical animal models of autoimmune. For example, FTS can attenuate disease manifestations in experimental autoimmune... experimental animal model of polyarthritis, which can be induced in inbred Lewis rats by immunization with Complete Freund’s adjuvant containing

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

    Science.gov (United States)

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

  15. Image-guided pro-angiogenic therapy in diabetic stroke mouse models using a multi-modal nanoprobe.

    Science.gov (United States)

    Bai, Ying-Ying; Gao, Xihui; Wang, Yuan-Cheng; Peng, Xin-Gui; Chang, Di; Zheng, Shuyan; Li, Cong; Ju, Shenghong

    2014-01-01

    The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. A home-made ανβ3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of β3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging. The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.

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

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nicole Leite Galvão-Coelho

    2017-09-01

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

  18. An animal model of emotional blunting in schizophrenia.

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    Charmaine Y Pietersen

    Full Text Available 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 rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.

  19. Three-dimensional modeler for animated images display system

    International Nuclear Information System (INIS)

    Boubekeur, Rania

    1987-01-01

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

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

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    Keiko Iwata

    2010-01-01

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

  1. Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model

    DEFF Research Database (Denmark)

    Østergaard, Jakob; Bjerre, Mette; RamachandraRao, Satish Posettihalli

    2012-01-01

    of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy. MATERIALS/METHODS: C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains......, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction. RESULTS: MBL aggravated diabetes......-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL...

  2. A New Tube Gastrostomy Model in Animal Experiments

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    Atakan Sezer

    2013-01-01

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

  3. A parsimonious approach to modeling animal movement data.

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    Yann Tremblay

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

  4. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

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    Mi XS

    2014-11-01

    Full Text Available Xue-Song Mi,1,2 Ti-Fei Yuan,3,4 Yong Ding,1 Jing-Xiang Zhong,1 Kwok-Fai So4,5 1Department of Ophthalmology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Psychology, Nanjing Normal University, Nanjing, People’s Republic of China; 4Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; 5Guangdong-Hongkong-Macau Institute of Central Nervous System, Jinan University, Guangzhou, People’s Republic of China Abstract: Diabetic retinopathy (DR is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. Keywords: animal model, in vitro culture, ex vivo culture, neurovascular dysfunction

  5. Modelling bronchopulmonary dysplasia in animals: arguments for the preterm rabbit model.

    Science.gov (United States)

    Salaets, Thomas; Gie, Andre; Tack, Bieke; Deprest, Jan; Toelen, Jaan

    2017-09-26

    Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked by an animal model for this disease. Prematurity remains the common denominator in the heterogeneous spectrum of human BPD, and preterm animal models thus have a clear translational advantage. Additional factors, like excessive oxygen, mechanical ventilation and infection, which frequently have been studied in animal models, can contribute to preterm lung injury however are not indispensable to develop BPD. The phenotype of human BPD is characterized by alveolar developmental arrest with extracellular matrix remodeling, signs of obstructive airway disease and pulmonary vascular disease. Many animal models mimic this phenotype and have their place in BPD research, but results should be interpreted bearing in mind the specific advantages and disadvantages of the model. Term mice and rats are well suited for basic explorative research on specific disease mechanisms, essential for the generation of new hypotheses, while the larger ventilated preterm baboons and lambs provide a good platform for the ultimate translation of these strategies towards clinical application. The preterm rabbit model seems a promising model as it the smallest model that includes a factor of prematurity and has a unique position between the small and large animal models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Animals Models of Human T Cell Leukemia Virus Type I Leukemogenesis.

    Science.gov (United States)

    Niewiesk, Stefan

    2016-01-01

    Infection with human T cell leukemia virus type I (HTLV-I) causes adult T cell leukemia (ATL) in a minority of infected individuals after long periods of viral persistence. The various stages of HTLV-I infection and leukemia development are studied by using several different animal models: (1) the rabbit (and mouse) model of persistent HTLV-I infection, (2) transgenic mice to model tumorigenesis by HTLV-I specific protein expression, (3) ATL cell transfers into immune-deficient mice, and (4) infection of humanized mice with HTLV-I. After infection, virus replicates without clinical disease in rabbits and to a lesser extent in mice. Transgenic expression of both the transactivator protein (Tax) and the HTLV-I bZIP factor (HBZ) protein have provided insight into factors important in leukemia/lymphoma development. To investigate factors relating to tumor spread and tissue invasion, a number of immune-deficient mice based on the severe combined immunodeficiency (SCID) or non-obese diabetic/SCID background have been used. Inoculation of adult T cell leukemia cell (lines) leads to lymphoma with osteolytic bone lesions and to a lesser degree to leukemia development. These mice have been used extensively for the testing of anticancer drugs and virotherapy. A recent development is the use of so-called humanized mice, which, upon transfer of CD34(+)human umbilical cord stem cells, generate human lymphocytes. Infection with HTLV-I leads to leukemia/lymphoma development, thus providing an opportunity to investigate disease development with the aid of molecularly cloned viruses. However, further improvements of this mouse model, particularly in respect to the development of adaptive immune responses, are necessary. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Diabetes Management at School: Application of the Healthy Learner Model

    Science.gov (United States)

    Bobo, Nichole; Kaup, Tara; McCarty, Patricia; Carlson, Jessie Parker

    2011-01-01

    Every child with diabetes deserves a school nurse with the capacity to effectively manage the disease at school. The school nurse needs knowledge and skills to confidently provide care and communicate with health care providers and families. The Healthy Learner Model for Chronic Condition Management provided a framework to eliminate the disjointed…

  8. Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model.

    Science.gov (United States)

    Lovati, Arianna B; Romanò, Carlo L; Monti, Lorenzo; Vassena, Christian; Previdi, Sara; Drago, Lorenzo

    2014-01-01

    Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated. A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

  9. Does PGE1 Vasodilator Prevent Orthopaedic Implant-Related Infection in Diabetes? Preliminary Results in a Mouse Model

    Science.gov (United States)

    Lovati, Arianna B.; Romanò, Carlo L.; Monti, Lorenzo; Vassena, Christian; Previdi, Sara; Drago, Lorenzo

    2014-01-01

    Background Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE1 vasodilator on the incidence of surgical infections in diabetic mice was investigated. Methodology A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE1 vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. Results The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE1 and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. Conclusions The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model. PMID:24718359

  10. Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model.

    Directory of Open Access Journals (Sweden)

    Arianna B Lovati

    Full Text Available BACKGROUND: Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated. METHODOLOGY: A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. RESULTS: The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. CONCLUSIONS: The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

  11. ANIMAL