Animal experimentation

OpenAIRE

Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

2016-01-01

Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

[Animal experimentation, computer simulation and surgical research].

Science.gov (United States)

Carpentier, Alain

2009-11-01

We live in a digital world In medicine, computers are providing new tools for data collection, imaging, and treatment. During research and development of complex technologies and devices such as artificial hearts, computer simulation can provide more reliable information than experimentation on large animals. In these specific settings, animal experimentation should serve more to validate computer models of complex devices than to demonstrate their reliability.

Monkeypox disease transmission in an experimental setting: prairie dog animal model.

Directory of Open Access Journals (Sweden)

Christina L Hutson

Full Text Available Monkeypox virus (MPXV is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox. MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively. Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission.

Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation.

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Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

2017-08-01

Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo-Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, "our" fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles - Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell-culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human-derived three-dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Towards ethically improved animal experimentation in the study of animal reproduction.

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Blache, D; Martin, G B; Maloney, S K

2008-07-01

The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds.

[Animal experimentation, animal welfare and scientific research].

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Tal, H

2013-10-01

Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals.

[Alternatives to animal experimentation v.s. animal rights terrorism].

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Kurosawa, Tsutomu Miki

2008-05-01

Systematic modern animal experimentation was established by Bernard Claude who wrote "An Introduction to the Study of Experimental Medicine" in 1865. At this point, the public was already asking that the pain and distress of experimental animals be reduced. For this, scientists, William Russell and Rex Burch in 1959 proposed the principles of alternatives to animal experimentation, the "3Rs". Since that time, animal welfare advocates have promoted the 3Rs concept in biomedical research communities. However, cruel animal experiments have continued and there are reports of radical extremists showing their opposition by invasion, arson, theft and even bombing of institutions involved, resulting in killing of the animals. SHAC, one extremist group believed to be animal welfare activitists was recognized as a terrorist group after the 9.11 tragedy in USA and the government viewed their activities very seriously. In 2001, British animal extremists invaded Japanese universities and stole laboratory resources; one individual was arrested and sentenced to prison for three years; Japanese who assisted in the incident were arrested and one was sentenced for one year. In 2006, SHAC USA members were prosecuted and sentenced for up to 6 years for their terrorism activities including arson. We need to consider the background of these activities which are financially supported by animal welfare advocates. The way we, as scientists who conduct such experiments can respond is by promoting alternatives to this experimentation. In Japan, the animal welfare law was revised in 2005 stressing the importance of 3Rs in scientific activities with animals. The promotion of 3Rs should be strengthened in the pharmaceutical community.

Invited review: Experimental design, data reporting, and sharing in support of animal systems modeling research.

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McNamara, J P; Hanigan, M D; White, R R

2016-12-01

The National Animal Nutrition Program "National Research Support Project 9" supports efforts in livestock nutrition, including the National Research Council's committees on the nutrient requirements of animals. Our objective was to review the status of experimentation and data reporting in animal nutrition literature and to provide suggestions for the advancement of animal nutrition research and the ongoing improvement of field-applied nutrient requirement models. Improved data reporting consistency and completeness represent a substantial opportunity to improve nutrition-related mathematical models. We reviewed a body of nutrition research; recorded common phrases used to describe diets, animals, housing, and environmental conditions; and proposed equivalent numerical data that could be reported. With the increasing availability of online supplementary material sections in journals, we developed a comprehensive checklist of data that should be included in publications. To continue to improve our research effectiveness, studies utilizing multiple research methodologies to address complex systems and measure multiple variables will be necessary. From the current body of animal nutrition literature, we identified a series of opportunities to integrate research focuses (nutrition, reproduction and genetics) to advance the development of nutrient requirement models. From our survey of current experimentation and data reporting in animal nutrition, we identified 4 key opportunities to advance animal nutrition knowledge: (1) coordinated experiments should be designed to employ multiple research methodologies; (2) systems-oriented research approaches should be encouraged and supported; (3) publication guidelines should be updated to encourage and support sharing of more complete data sets; and (4) new experiments should be more rapidly integrated into our knowledge bases, research programs and practical applications. Copyright © 2016 American Dairy Science Association

Experimental animal models for COPD: a methodological review

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Vahideh Ghorani

2017-05-01

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

[Ethical issue in animal experimentation].

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Parodi, André-Laurent

2009-11-01

In the 1970s, under pressure from certain sections of society and thanks to initiatives by several scientific research teams, committees charged with improving the conditions of laboratory animals started to be created, first in the United States and subsequently in Europe. This led to the development of an ethical approach to animal experimentation, taking into account new scientific advances. In addition to the legislation designed to provide a legal framework for animal experimentation and to avoid abuses, this ethical approach, based on the concept that animals are sentient beings, encourages greater respect of laboratory animals and the implementation of measures designed to reduce their suffering. Now, all animal experiments must first receive ethical approval--from in-house committees in the private sector and from regional committees for public institutions. Very recently, under the impetus of the French ministries of research and agriculture, the National committee for ethical animal experimentation published a national ethical charter on animal experimentation, setting the basis for responsible use of animals for scientific research and providing guidelines for the composition and functioning of ethics committees. Inspired by the scientific community itself this ethical standardization should help to assuage--but not eliminate--the reticence and hostility expressed by several sections of society.

Animal model of atherosclerosis using rabbit experimentally induced by combination of X-ray and hypercholesterolemia

International Nuclear Information System (INIS)

Ishiyama, Tomotoshi; Sawai, Takashi; Okuma, Tsuneo; Mori, Shozo

1995-01-01

An attempt was made to prepare an animal model of atherosclerosis similar to human lesions. The experimental animals were male Japanese white rabbits weighting about 2 kg. Hypercholesterolemia was experimentally induced by giving a 1% cholesterol diet. Four weeks later, a single dose of 45 Gy was delivered to the femur to produce vascular changes. Soon after irradiation, immunohistochemical examination revealed the adhesion and invasion of macrophages to endothelial cells, followed by accumulation of foam cells and thickness of the intimal plaques. Three months after irradiation, these thickened plaques became fibrotic, calcified, and necrotic. The tunica media was thinned and the internal elastic lamella was destroyed. Irradiated arteries exhibited not only severe narrowing of the lumen but also aneurysmal dilation and the lesions of the irradiated arteries resembled human atherosclerosis. In conclusion, the atherosclerotic model produced by combining experimental hypercholesterolemia and X-ray irradiaiton may serve as a useful model for studies on atherosclerosis because it can be prepared with no need of complicated or time-consuming procedures. (N.K.)

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

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

2014-01-01

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

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...

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

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Ionuț Tudorancea

Full Text Available Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551, while the increment is lower it the next two intervals (40-42°C and 42-44°C with 0.291°C/ s (R2 = 0.9337 and 0.136°C/ s (R2 = 0.7894 respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

Establishment for quality control of experimental animal

International Nuclear Information System (INIS)

Kim, Tae Hwan; Kim, Soo Kwan; Kim, Tae Kyoung

1999-06-01

Until now, because we have imported experimental animal from foreign experimental animal corporation, we could have saved money by establishing the quality control of animal in barrier system. In order to improve the quality of animal experiment and efficiency of biomedical study, it is indispensable to control many factors that effect in the experiment. Therefore, it is essential to organize the system of laboratory animal care for enhancing reliability and revivability of experimental results. The purpose of the present investigation was to establish the quality control system of experimental animals that we can provide good quality animals according to the experimental condition of each investigator although the exact quality control system to estimate the infection of bacteria and virus easily remains ill-defined yet. Accordingly, we established the useful quality control system for microbiologic monitoring and environmental monitoring to protect experimental animal from harmful bacteria and virus

Establishment for quality control of experimental animal

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae Hwan; Kim, Soo Kwan; Kim, Tae Kyoung

1999-06-01

Until now, because we have imported experimental animal from foreign experimental animal corporation, we could have saved money by establishing the quality control of animal in barrier system. In order to improve the quality of animal experiment and efficiency of biomedical study, it is indispensable to control many factors that effect in the experiment. Therefore, it is essential to organize the system of laboratory animal care for enhancing reliability and revivability of experimental results. The purpose of the present investigation was to establish the quality control system of experimental animals that we can provide good quality animals according to the experimental condition of each investigator although the exact quality control system to estimate the infection of bacteria and virus easily remains ill-defined yet. Accordingly, we established the useful quality control system for microbiologic monitoring and environmental monitoring to protect experimental animal from harmful bacteria and virus.

Public perceptions of animal experimentation across Europe.

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von Roten, Fabienne Crettaz

2013-08-01

The goal of this article is to map out public perceptions of animal experimentation in 28 European countries. Postulating cross-cultural differences, this study mixes country-level variables (from the Eurostat database) and individual-level variables (from Eurobarometer Science and Technology 2010). It is shown that experimentation on animals such as mice is generally accepted in European countries, but perceptions are divided on dogs and monkeys. Between 2005 and 2010, we observe globally a change of approval on dogs and monkeys, with a significant decrease in nine countries. Multilevel analysis results show differences at country level (related to a post-industrialism model) and at individual level (related to gender, age, education, proximity and perceptions of science and the environment). These results may have consequences for public perceptions of science and we call for more cross-cultural research on press coverage of animal research and on the level of public engagement of scientists doing animal research.

The '3Is' of animal experimentation.

Science.gov (United States)

2012-05-29

Animal experimentation in scientific research is a good thing: important, increasing and often irreplaceable. Careful experimental design and reporting are at least as important as attention to welfare in ensuring that the knowledge we gain justifies using live animals as experimental tools.

Animal experimentation-Part II: In periodontal research

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T K Pal

2015-01-01

Full Text Available Animals contribute to the development of medical and dental sciences by being sacrificed in the hands of scientists. The experimental design demands a specific type of animal to be used for experimentation. Each animal needs proper handling, care, and diet. Alongside specific advantages and disadvantages pertaining to each type of animal need to be understood well depending on the type of study/experiment. It is important for the researcher to know the disease susceptibility of each animal. The purpose of this paper is to highlight the salient factors that need to be considered for animal experimentations.

Animal experimentation--a personal view.

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Gershoff, Stanley N

2009-02-01

Disagreement about the use of animals in biomedical research has resulted in absurd positions by both sides. Increasingly, some zealots against animal experimentation have resorted to violence or other illegal acts to support their points of view. The value of animal research in providing better health for man and animals is incontrovertible. This is illustrated by references to animal research in the field of nutrition.

[The ethics of animal experimentation].

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Goffi, Jean-Yves

2013-01-01

The paper starts with a short definition of animal experimentation, then three main approaches to the practice are considered: unconditional approval (as advocated by Claude Bernard), conditional and restricted approval (as advocated by Peter Singer) and strict prohibition (as advocated by Tom Regan and Gary Francione). It is argued that what is actually approved or condemned in animal experimentation is the value of the scientific enterprise.

Experimental animal studies of radon and cigarette smoke

International Nuclear Information System (INIS)

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

1992-01-01

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

Animal models of osteoporosis - necessity and limitations

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Turner A. Simon

2001-06-01

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

[Contribution of animal experimentation to pharmacology].

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Sassard, Jean; Hamon, Michel; Galibert, Francis

2009-11-01

Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

Animal models for testing anti-prion drugs.

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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.

Multivariate Analysis for Animal Selection in Experimental Research

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Renan Mercuri Pinto

2015-02-01

Full Text Available Background: Several researchers seek methods for the selection of homogeneous groups of animals in experimental studies, a fact justified because homogeneity is an indispensable prerequisite for casualization of treatments. The lack of robust methods that comply with statistical and biological principles is the reason why researchers use empirical or subjective methods, influencing their results. Objective: To develop a multivariate statistical model for the selection of a homogeneous group of animals for experimental research and to elaborate a computational package to use it. Methods: The set of echocardiographic data of 115 male Wistar rats with supravalvular aortic stenosis (AoS was used as an example of model development. Initially, the data were standardized, and became dimensionless. Then, the variance matrix of the set was submitted to principal components analysis (PCA, aiming at reducing the parametric space and at retaining the relevant variability. That technique established a new Cartesian system into which the animals were allocated, and finally the confidence region (ellipsoid was built for the profile of the animals’ homogeneous responses. The animals located inside the ellipsoid were considered as belonging to the homogeneous batch; those outside the ellipsoid were considered spurious. Results: The PCA established eight descriptive axes that represented the accumulated variance of the data set in 88.71%. The allocation of the animals in the new system and the construction of the confidence region revealed six spurious animals as compared to the homogeneous batch of 109 animals. Conclusion: The biometric criterion presented proved to be effective, because it considers the animal as a whole, analyzing jointly all parameters measured, in addition to having a small discard rate.

Induction of a chronic myocardial infarction in the laboratory animal - experimental model

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POP, IONEL CIPRIAN; GRAD, NICOLAE-OVIDIU; PESTEAN, COSMIN; TAULESCU, MARIAN; MIRCEAN, MIRCEA; MIRONIUC, ION-AUREL

2013-01-01

Introduction Ischemic heart disease is a major public health problem in western countries. Appropriate animal experimental models of chronic myocardial infarction is an essential first step in order to investigate and develop new therapeutic interventions. Aim The aim of this study was to find an optimal place for a coronary artery ligation to induce an optimal chronic myocardial infarction and also a new heart approach that will not require oro-tracheal intubation. Material and methods To achieve these goals we used a group of rabbits and after induction of anesthesia and cardiac exposure by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side we performed three different left anterior descending artery (LAD) ligation at different distances (5, 10 and 15 mm) in relation to the apex. Thirty days after the acute myocardial infarction, we correlated laboratory investigations (serology, ECG, cardiac ultrasound) with histopathological findings. Results Heart approach achieved by rib osteotomy (rib III, IV and V) at the costo-sternal junction level on the right side, maintains the integrity of the ribcage, allowing it to take part in respiratory movements and the animal model does not need oro-tracheal intubation. Ligation of LAD at 15 mm from the apex was incompatible with life; ligation of LAD at 5 mm from the apex does not achieved transmural myocardial infarction and ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle which also involved the distal part of the interventricular septum. Conclusion Ligation of LAD at 10 mm from the apex achieved a transmural myocardial infarction of the left ventricle, is in an easily accessible area from technical point of view, it is sufficiently expanded to induce hemodynamic effects that can be quantified with paraclinical examination and also it is compatible with the experimental animal life. If the heart is approached by rib III, IV and V

Practical application of stereological methods in experimental kidney animal models.

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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.

The rights of man and animal experimentation.

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Martin, J

1990-01-01

Since emotions give contradictory signals about animal experimentation in medical science, man's relationship to animals must be based upon reason. Thomas Aquinas argues that man is essentially different from animals because man's intellectual processes show evidence of an abstract mechanism not possessed by animals. Man's rights arise in association with this essential difference. The consequence is that only man possesses true rights by Aquinas's definition; animals have them only by analogy. However, cruelty to animals is illicit and they should be protected, principally not because they have rights, but because he who is cruel to animals is more likely to be cruel to his fellowman. If there is a need for animal experimentation in science for the good of man, this approach gives philosophical justification for experimentation, since man's well-being must come before that of animals because of his unique possession of rights. However, those experiments should be carried out in the kindest way possible, to promote kindness towards man. To see man as solely part of a biological continuum in competition for rights with those beings close to him biologically, detracts from man's dignity. PMID:2135948

[Animal experimentation in the discovery and production of veterinary vaccines].

Science.gov (United States)

Audonnet, J Ch; Lechenet, J; Verschuere, B

2007-08-01

Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.

Animal models of erectile dysfunction

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Snehlata V Gajbhiye

2015-01-01

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

Animal experimentation and scientific knowledge: a thought style?

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Thales de Astrogildo e Tréz

2010-12-01

Full Text Available Animal experimentation, besides a research method extensively applied in the production of scientific knowledge, is also considered essential to science and with undeniable historical relevance in advances in human health. In this survey, a questionnaire was applied to a group of researchers involved with research based on non-animal models (n =18, and to another group involved with research based on animal models (n =18. The data analysis was grounded in Ludwik Fleck (1896 -1961 epistemological assumptions. The results suggested that there are at least two thought styles operating in consonance on the same research problem (advances in human health conditions with significantly different conceptions not only concerning the research practices involved, but also the historical conceptions related to the role of animal experimentation.A experimentação animal, além de método amplamente aplicado na produção do conhecimento científico, é considerada como essencial à ciência e com valor histórico inegável no progresso das condições de saúde humana. Neste levantamento, um questionário foi aplicado a um grupo de pesquisadores com trabalhos baseados em modelos não-animais (n =18 e a outro grupo com trabalhos baseados em modelos animais (n =18. A análise de dados se baseou nos pressupostos epitemológicos de Ludwik Fleck (1896-1961. Os dados sugerem que existem pelo menos dois estilos de pensamento operando em consonância sobre o mesmo problema de pesquisa (avanços nas condições de saúde humana, com concepções significativamente diferentes sobre as práticas de pesquisa envolvidas, assim como as concepções históricas relacionadas ao papel da experimentação animal.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

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Aya Nakae

2011-01-01

Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

Science.gov (United States)

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS).

Science.gov (United States)

Glatigny, Simon; Bettelli, Estelle

2018-01-08

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens. In addition, genetic susceptibility and environmental triggers likely contribute to the initiation of the disease. At this time, there is no cure for MS, but several disease-modifying therapies (DMTs) are available to control and slow down disease progression. A good number of these DMTs were identified and tested using animal models of MS referred to as experimental autoimmune encephalomyelitis (EAE). In this review, we will recapitulate the characteristics of EAE models and discuss how they help shed light on MS pathogenesis and help test new treatments for MS patients. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

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

Science.gov (United States)

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

2016-01-01

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

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.

Environmental enrichment in farm, zoo, companion and experimental animals

OpenAIRE

Vučinić Marijana

2009-01-01

The paper deals with environmental enrichment for domestic animals at farms, animals in zoos, experimental animals and pet animals. Also, the paper defines and describes different strategies of environmental enrichment. Environmental enrichment is a simple and effective mean of prevention of boredom, behavioral disorders as well as an effective mean of improving animal welfare in farm, zoo, companion and experimental animals. Different items and materials may be used for environmental enrichm...

Mutant mice: experimental organisms as materialised models in biomedicine.

Science.gov (United States)

Huber, Lara; Keuck, Lara K

2013-09-01

Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Animal Experimentation: Bringing Ethical Issues into Biology Teaching.

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Van Rooy, Wilhelmina

2000-01-01

There are many possibilities for the use of controversial issues such as animal experimentation in biology classrooms. Outlines a series of three lessons that asked senior biology students to consider the issue of animal experimentation from three perspectives. (Author/LM)

Animal models of exercise and obesity.

Science.gov (United States)

Kasper, Christine E

2013-01-01

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

An Experimental Animal Model for Abdominal Fascia Healing after Surgery

DEFF Research Database (Denmark)

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

2013-01-01

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

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...

The rights of man and animal experimentation.

OpenAIRE

Martin, J

1990-01-01

Since emotions give contradictory signals about animal experimentation in medical science, man's relationship to animals must be based upon reason. Thomas Aquinas argues that man is essentially different from animals because man's intellectual processes show evidence of an abstract mechanism not possessed by animals. Man's rights arise in association with this essential difference. The consequence is that only man possesses true rights by Aquinas's definition; animals have them only by analog...

Experimental models of demyelination and remyelination.

Science.gov (United States)

Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

2017-08-29

Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Animal models of cardiovascular diseases.

Science.gov (United States)

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

2011-01-01

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

Animal experimentation in Japan: regulatory processes and application for microbiological studies.

Science.gov (United States)

Takahashi-Omoe, H; Omoe, K

2007-07-01

We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

Animal Experimentation in High Schools

Science.gov (United States)

Ansevin, Kystyna D.

1970-01-01

Recommends that teacher and student be provided with the broadest possible spectrum of meaningful and feasible experiments in which the comfort of the experimental animal is protected by the design of the experiment. (BR)

[The 1, 2, 3 of laboratory animal experimentation].

Science.gov (United States)

Romero-Fernandez, Wilber; Batista-Castro, Zenia; De Lucca, Marisel; Ruano, Ana; García-Barceló, María; Rivera-Cervantes, Marta; García-Rodríguez, Julio; Sánchez-Mateos, Soledad

2016-06-01

The slow scientific development in Latin America in recent decades has delayed the incorporation of laboratory animal experimentation; however, this situation has started to change. Today, extraordinary scientific progress is evident, which has promoted the introduction and increased use of laboratory animals as an important tool for the advancement of biomedical sciences. In the aftermath of this boom, the need to provide the scientific community with training and guidance in all aspects related to animal experimentation has arisen. It is the responsibility of each country to regulate this practice, for both bioethical and legal reasons, to ensure consideration of the animals' rights and welfare. The following manuscript is the result of papers presented at the International Workshop on Laboratory Animal Testing held at the Technical University of Ambato, Ecuador; it contains information regarding the current state of affairs in laboratory animal testing and emphasizes critical aspects such as main species used, ethical and legal principles, and experimental and alternative designs for animal use. These works aim to ensure good practices that should define scientific work. This document will be relevant to both researchers who aim to newly incorporate animal testing into their research and those who seek to update their knowledge.

Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?

Directory of Open Access Journals (Sweden)

Melina C den Haan

Full Text Available Human mesenchymal stromal cells (MSCs have been reported to preserve cardiac function in myocardial infarction (MI models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs, since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.Animal models for cardiac MSC therapy appear less robust than initially envisioned.

Retinal Cell Degeneration in Animal Models

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Masayuki Niwa

2016-01-01

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

Hemorrhoids: an experimental model in monkeys

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Plapler Hélio

2006-01-01

Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

Critical overview of all available animal models for abdominal wall hernia research.

Science.gov (United States)

Vogels, R R M; Kaufmann, R; van den Hil, L C L; van Steensel, S; Schreinemacher, M H F; Lange, J F; Bouvy, N D

2017-10-01

Since the introduction of the first prosthetic mesh for abdominal hernia repair, there has been a search for the "ideal mesh." The use of preclinical or animal models for assessment of necessary characteristics of new and existing meshes is an indispensable part of hernia research. Unfortunately, in our experience there is a lack of consensus among different research groups on which model to use. Therefore, we hypothesized that there is a lack of comparability within published animal research on hernia surgery due to wide range in experimental setup among different research groups. A systematic search of the literature was performed to provide a complete overview of all animal models published between 2000 and 2014. Relevant parameters on model characteristics and outcome measurement were scored on a standardized scoring sheet. Due to the wide range in different animals used, ranging from large animal models like pigs to rodents, we decided to limit the study to 168 articles concerning rat models. Within these rat models, we found wide range of baseline animal characteristics, operation techniques, and outcome measurements. Making reliable comparison of results among these studies is impossible. There is a lack of comparability among experimental hernia research, limiting the impact of this experimental research. We therefore propose the establishment of guidelines for experimental hernia research by the EHS.

Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

DEFF Research Database (Denmark)

Møller, Peter; Risom, Lotte; Lundby, Carsten

2008-01-01

The objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility......, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid...... in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity....

Animal Models of Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Carlos Zaragoza

2011-01-01

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

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

Refining animal experiments: the first Brazilian regulation on animal experimentation.

Science.gov (United States)

de A e Tréz, Thales

2010-06-01

The very first law on animal experimentation has been approved recently in Brazil, and now is part of a set of the legal instruments that profile the Brazilian government's attitude toward the use of animals in experiments. Law 11794/08 establishes a new legal instrument that will guide new methods of conduct for ethics committees, researchers and representatives of animal protection societies. This comment aims to analyse critically the implications that this law brings to Brazilian reality. The link between it and the Russell and Burch's Three Rs concept is defined, and certain problems are identified. The conclusion is that the body of the law emphasises the refinement of animal experiments, but gives little importance to the principles of reduction and replacement.

Secrets and lies: "selective openness" in the apparatus of animal experimentation.

Science.gov (United States)

Holmberg, Tora; Ideland, Malin

2012-04-01

Researchers and other (human) actors within the apparatus of animal experimentation find themselves in a tight corner. They rely on public acceptance to promote their legitimacy and to receive funding. At the same time, those working with animal experimentation take risks by going public, fearing that the public will misunderstand their work and animal rights activists may threaten them. The dilemma that emerges between openness and secrecy is fairly prevalent in scientific culture as a whole, but the apparatus of animal experimentation presents specific patterns of technologies of secrets. The aim of the paper is to describe and analyse the meanings of secrets and openness in contemporary animal experimentation. We suggest that these secrets--or "selective openness"--can be viewed as grease in the apparatus of animal experimentation, as a unifying ingredient that permits maintenance of status quo in human/animal relations and preserves existing institutional public/ science relations.

Advances in Animal Models of Hepatitis B Virus Infection

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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.

Animal model of thermal injuries

Directory of Open Access Journals (Sweden)

F. Bečić

2003-11-01

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

Animal models

DEFF Research Database (Denmark)

Gøtze, Jens Peter; Krentz, Andrew

2014-01-01

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

Animal Experimentation: Issues for the 1980s.

Science.gov (United States)

Zola, Judith C.; And Others

1984-01-01

Examines the extent to which issues related to animal experimentation are in conflict and proposes choices that might least comprise them. These issues include animal well-being, human well-being, self-interest of science, scientific validity and responsibility, progress in biomedical and behavioral science, and the future quality of medical care.…

Experimental psychiatric illness and drug abuse models: from human to animal, an overview.

Science.gov (United States)

Edwards, Scott; Koob, George F

2012-01-01

Preclinical animal models have supported much of the recent rapid expansion of neuroscience research and have facilitated critical discoveries that undoubtedly benefit patients suffering from psychiatric disorders. This overview serves as an introduction for the following chapters describing both in vivo and in vitro preclinical models of psychiatric disease components and briefly describes models related to drug dependence and affective disorders. Although there are no perfect animal models of any psychiatric disorder, models do exist for many elements of each disease state or stage. In many cases, the development of certain models is essentially restricted to the human clinical laboratory domain for the purpose of maximizing validity, whereas the use of in vitro models may best represent an adjunctive, well-controlled means to model specific signaling mechanisms associated with psychiatric disease states. The data generated by preclinical models are only as valid as the model itself, and the development and refinement of animal models for human psychiatric disorders continues to be an important challenge. Collaborative relationships between basic neuroscience and clinical modeling could greatly benefit the development of new and better models, in addition to facilitating medications development.

Basic mechanisms of MCD in animal models.

Science.gov (United States)

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

2009-09-01

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

The perception of animal experimentation ethics among Indian teenage school pupils.

Science.gov (United States)

Kim, Justin Namuk; Choi, Eun Hee; Kim, Soo-Ki

2017-03-01

To promote awareness of animal experimentation ethics among teenagers, we created an educational pamphlet and an accompanying questionnaire. One hundred Indian teenage school pupils were given the pamphlet and subsequently surveyed with the questionnaire, to evaluate: a) their perception of animal experimentation ethics; and b) their opinion on the effectiveness of the pamphlet, according to gender and school grade/age. There was a significant correlation between grade/age and support for animal experimentation, i.e. senior students were more inclined to show support for animal experimentation. There was also a significant correlation between gender and perception of the need to learn about animal experimentation ethics, with girls more likely to feel the need to learn about ethics than boys. In addition, the four questions relating to the usefulness of the pamphlet, and student satisfaction with its content, received positive responses from the majority of the students. Even though the pamphlet was concise, it was apparent that three quarters of the students were satisfied with its content. Gender and age did not influence this level of satisfaction. Overall, our study shows that there is a significant correlation between a pupil`s school grade/age and their support for animal experimentation, and that there is also a significant correlation between gender and the perceived need to learn about animal experimentation ethics. This pilot scheme involving an educational pamphlet and questionnaire could be beneficial in helping to formulate basic strategies for educating teenage school pupils about animal ethics. 2017 FRAME.

Systematic heterogenization for better reproducibility in animal experimentation.

Science.gov (United States)

Richter, S Helene

2017-08-31

The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Experimental model of the burn wound topical treatment

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Amra Čabaravdić

2003-11-01

Full Text Available AbstractBACKGROUND AND PURPOSE:Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burninducement and effects of the ointment containing natural plants on the process of burn healing.MATERIAL AND METHODS:Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1 of 15 animals each (mice and rats, while control group (2 of 10 animals each (mice and rats that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test.CONCLUSION:Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

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...

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

Science.gov (United States)

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

2018-01-01

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

Chimeric animal models in human stem cell biology.

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

2009-01-01

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

Animal models of cardiac cachexia.

Science.gov (United States)

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

2016-09-15

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Aspects of animal models for major neuropsychiatric disorders

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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.

Teaching Neurophysiology, Neuropharmacology, and Experimental Design Using Animal Models of Psychiatric and Neurological Disorders

Science.gov (United States)

Morsink, Maarten C.; Dukers, Danny F.

2009-01-01

Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Henipavirus Infections: Lessons from Animal Models

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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.

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

Science.gov (United States)

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

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

They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice.

Science.gov (United States)

Kehinde, Elijah O

2013-01-01

The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. © 2013 S. Karger AG, Basel.

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

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Apurba Mukherjee

2009-06-01

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

Development of experimental alloxan model of diabetes mellitus

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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.

Animal models of GM2 gangliosidosis: utility and limitations

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Lawson, Cheryl A; Martin, Douglas R

2016-01-01

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

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

OpenAIRE

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

Tobacco experimental model to induce urinary bladder neoplasms

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José Alexandre Colli Neto

2014-01-01

Full Text Available OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin and the concentration of carbon dioxide (CO2 confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

Expanding the three Rs to meet new challenges in humane animal experimentation.

Science.gov (United States)

Schuppli, Catherine A; Fraser, David; McDonald, Michael

2004-11-01

The Three Rs are the main principles used by Animal Ethics Committees in the governance of animal experimentation, but they appear not to cover some ethical issues that arise today. These include: a) claims that certain species should be exempted on principle from harmful research; b) increased emphasis on enhancing quality of life of research animals; c) research involving genetically modified (GM) animals; and d) animals bred as models of disease. In some cases, the Three Rs can be extended to cover these developments. The burgeoning use of GM animals in science calls for new forms of reduction through improved genetic modification technology, plus continued attention to alternative approaches and cost-benefit analyses that include the large numbers of animals involved indirectly. The adoption of more expanded definitions of refinement that go beyond minimising distress will capture concerns for enhancing the quality of life of animals through improved husbandry and handling. Targeting refinement to the unpredictable effects of gene modification may be difficult; in these cases, careful attention to monitoring and endpoints are the obvious options. Refinement can also include sharing data about the welfare impacts of gene modifications, and modelling earlier stages of disease, in order to reduce the potential suffering caused to disease models. Other issues may require a move beyond the Three Rs. Certain levels of harm, or numbers and use of certain species, may be unacceptable, regardless of potential benefits. This can be addressed by supplementing the utilitarian basis of the Three Rs with principles based on deontological and relational ethics. The Three Rs remain very useful, but they require thoughtful interpretation and expansion in order for Animal Ethics Committees to address the full range of issues in animal-based research.

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

Experimental, statistical, and biological models of radon carcinogenesis

International Nuclear Information System (INIS)

Cross, F.T.

1991-09-01

Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

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

How to become a top model: impact of animal experimentation on human Salmonella disease research.

Science.gov (United States)

Tsolis, Renée M; Xavier, Mariana N; Santos, Renato L; Bäumler, Andreas J

2011-05-01

Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on Salmonella serotypes. This article reviews important milestones in the use of animal models to study human Salmonella disease and identify research needs to guide future work.

An animal model to train Lichtenstein inguinal hernia repair

DEFF Research Database (Denmark)

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

2013-01-01

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

Precise MRI-based stereotaxic surgery in large animal models

DEFF Research Database (Denmark)

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

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

The rabbit as an experimental model in laryngology

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Carneiro, Christiano de Giacomo

2009-06-01

Full Text Available Introduction: In the research in laryngology we normally use animal models. The animal experimentation may also contribute largely for this evolution, mainly for the easy access compared to human larynxes and for they are more easily controlled. Objective: The objective of this work is to analyze the laryngofissure with vocal cords graft as an experimental surgical technique in male adult rabbits. Method: We studied 46 New Zealand albino rabbits submitted to microsurgery in both vocal cords with autologous unilateral or bilateral graft of fat or fascia. Results: There were 4 losses of 3 animals until the first week of the postoperative period and another after 19 days after surgery. In the subsequent animals there were no infection, hematoma or sutures dehiscence. Conclusion: The study enables the conclusion that the experimental laryngofissure in rabbits is a safe method that may be used for laryngological studies.

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

Computer-animated model of accommodation and presbyopia.

Science.gov (United States)

Goldberg, Daniel B

2015-02-01

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

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.

Animal models of tic disorders: A translational perspective

Science.gov (United States)

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

2014-01-01

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

Experimental models of developmental hypothyroidism.

Science.gov (United States)

Argumedo, G S; Sanz, C R; Olguín, H J

2012-02-01

Hypothyroidism is a systemic disease resulting from either thyroid gland's anatomical and functional absence or lack of hypophyseal stimulation, both of which can lead to deficiency in thyroid hormone (TH) production. TH is essential for human and animal development, growth, and function of multiple organs. Children with deficient TH can develop alterations in central nervous system (CNS), striated muscle, bone tissue, liver, bone marrow, and cardiorespiratory system. Among the clinical outlook are signs like breathing difficulty, cardiac insufficiency, dysphagia, and repeated bronchial aspiration, constipation, muscle weakness, cognitive alterations, cochlear dysfunction, reduced height, defects in temperature regulation, anaemia, jaundice, susceptibility to infection, and others. Experimental and clinical studies have shown that TH is very essential for normal brain development. Other research work based on mice pointed out that a reduced level of TH in pregnant mother leads to congenital hypothyroidism in animal models and it is associated with mental retardation, deep neurologic deficiency that impacts on cognitive, learning, and memory functions. The principal experimental model studies that have focused on hypothyroidism are reviewed in this study. This is important on considering the fact that almost all animal species require thyroid hormones for their metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

Science.gov (United States)

Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel

2014-01-01

Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in

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.

Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?

Directory of Open Access Journals (Sweden)

Chunyan Xue

2015-01-01

Full Text Available Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases.

Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

International Nuclear Information System (INIS)

Bhattacharyya, Maryka H.

2009-01-01

Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure, within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.

Social Stress in Rats : An Animal Model of Depression?

NARCIS (Netherlands)

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

1995-01-01

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

Inflammation-induced preterm lung maturation: lessons from animal experimentation.

Science.gov (United States)

Moss, Timothy J M; Westover, Alana J

2017-06-01

Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development.

Science.gov (United States)

Kinter, Lewis B; DeGeorge, Joseph J

2016-12-01

Human discovery of pharmacologically active substances is arguably the oldest of the biomedical sciences with origins >3500 years ago. Since ancient times, four major transformations have dramatically impacted pharmaceutical development, each driven by advances in scientific knowledge, technology, and/or regulation: (1) anesthesia, analgesia, and antisepsis; (2) medicinal chemistry; (3) regulatory toxicology; and (4) targeted drug discovery. Animal experimentation in pharmaceutical development is a modern phenomenon dating from the 20th century and enabling several of the four transformations. While each transformation resulted in more effective and/or safer pharmaceuticals, overall attrition, cycle time, cost, numbers of animals used, and low probability of success for new products remain concerns, and pharmaceutical development remains a very high risk business proposition. In this manuscript we review pharmaceutical development since ancient times, describe its coevolution with animal experimentation, and attempt to predict the characteristics of future transformations. © 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.

Irradiation Design for an Experimental Murine Model

International Nuclear Information System (INIS)

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

2010-01-01

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

International Nuclear Information System (INIS)

Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

1977-01-01

The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

The Nuremberg Code subverts human health and safety by requiring animal modeling

Directory of Open Access Journals (Sweden)

Greek Ray

2012-07-01

Full Text Available Abstract Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

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

OpenAIRE

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

2016-01-01

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

Injury Based on Its Study in Experimental Models

Directory of Open Access Journals (Sweden)

M. Mendes-Braz

2012-01-01

Full Text Available The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered.

Animal models of dementia

DEFF Research Database (Denmark)

Olsson, I. Anna S.; Sandøe, Peter

2011-01-01

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

Criticizing animal experimentation, at my peril.

Science.gov (United States)

Eisenman, Stephen F

2016-01-01

Initiatives leading to even modest reduction in animal use at major U.S. universities are likely to continue to face strong opposition. At least, that's the conclusion the author draws from his efforts at Northwestern University. In fact, despite a growing body of evidence that animal-based research is flawed at best and misleading or un-scientific at worst its use is growing at Northwestern and elsewhere. Moreover, recent discoveries concerning animal consciousness and emotion have not led to notable improvements in the conditions in which AWA protected animals live at the Chicago vivarium. There, animals languish in featureless rooms or sterile cages without access to daylight and with little opportunity to express their natural behaviors and aptitudes. The writer's public exposure of these conditions led to a fierce backlash. Unless there is a significant change in laboratory and university culture, change will only come when the marketplace and funding agencies demand better and more reliable, non-animal models for the testing of drug toxicity and effectiveness.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones.

Science.gov (United States)

Nuss, Katja M R; Auer, Joerg A; Boos, Alois; von Rechenberg, Brigitte

2006-08-15

The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

Directory of Open Access Journals (Sweden)

Boos Alois

2006-08-01

Full Text Available Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

Science.gov (United States)

Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

2006-01-01

Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials. PMID:16911787

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

NARCIS (Netherlands)

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

1999-01-01

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

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

Ethical and Animal Welfare Considerations in Relation to Species Selection for Animal Experimentation.

Science.gov (United States)

Webster, John

2014-12-03

Ethical principles governing the conduct of experiments with animals are reviewed, especially those relating to the choice of species. Legislation requires that the potential harm to animals arising from any procedure should be assessed in advance and justified in terms of its possible benefit to society. Potential harms may arise both from the procedures and the quality of the animals' lifetime experience. The conventional approach to species selection is to use animals with the "lowest degree of neurophysiological sensitivity". However; this concept should be applied with extreme caution in the light of new knowledge. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. A set of responsibilities is outlined for each category of moral agent. These include regulators, operators directly concerned with the conduct of scientific experiments and toxicology trials, veterinarians and animal care staff; and society at large.

A device for external γ-irradiation of experimental animals

International Nuclear Information System (INIS)

Ivanitskaya, N.F.; Talakin, Yu.N.; Lekakh, V.A.

1992-01-01

A device was developed for external gamma-irradiation of experimental animals including a radiation source, a device for fixation of the total animal or a segment of its body in the focus of irradiation, and a shilding screen. To widen the sphere of this device application by making possible a simultaneous radiation exposure of a group of animals under various radiation schedules, the device involves two discs with a common axis. The lower disc is provided with an electric drive and containers with animals are placed on it, and the upper disc is for the shielding screen. The device is supplied with an operation block

An Overview of Animal Models for Arthropod-Borne Viruses.

Science.gov (United States)

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

2017-06-01

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

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

[Reduction of animal experiments in experimental drug testing].

Science.gov (United States)

Behrensdorf-Nicol, H; Krämer, B

2014-10-01

In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.

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.

Modelling Farm Animal Welfare

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Chérie E. Part

2013-05-01

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

The European politics of animal experimentation: From Victorian Britain to 'Stop Vivisection'.

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Germain, Pierre-Luc; Chiapperino, Luca; Testa, Giuseppe

2017-08-01

This paper identifies a common political struggle behind debates on the validity and permissibility of animal experimentation, through an analysis of two recent European case studies: the Italian implementation of the European Directive 2010/63/EC regulating the use of animals in science, and the recent European Citizens' Initiative (ECI) 'Stop Vivisection'. Drawing from a historical parallel with Victorian antivivisectionism, we highlight important threads in our case studies that mark the often neglected specificities of debates on animal experimentation. From the representation of the sadistic scientist in the XIX century, to his/her claimed capture by vested interests and evasion of public scrutiny in the contemporary cases, we show that animals are not simply the focus of the debate, but also a privileged locus at which much broader issues are being raised about science, its authority, accountability and potential misalignment with public interest. By highlighting this common socio-political conflict underlying public controversies around animal experimentation, our work prompts the exploration of modes of authority and argumentation that, in establishing the usefulness of animals in science, avoid reenacting the traditional divide between epistemic and political fora. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review.

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Mazensky, David; Flesarova, Slavka; Sulla, Igor

2017-12-01

Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

COMPARISON OF ANTI - INFLAMMATORY ACTIVITY OF ALPINIA GALANGAL IN THREE EXPERIMENTAL ANIMAL MODELS

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Venuturumilli Lakshmi

2015-05-01

Full Text Available Inflammation is not a disease but a non - specific response of the body defence 1 . Anti - inflammatory drugs have become popular because of their ability in controlling the inflammatory reaction and mitigating the suffering in such clinical situations. Edema represents the early phase of inflammation. 2 In the present study acute and subacute experimental methods were compared with standard drug Indomethacin. R at hind paw edema, formalin induced peritonitis in mice were used as acute methods, paper disc induced granuloma in rats was used as subacute method. Institutional animal ethics committee permission was taken for all the methods as per CPCSEA guide lines. Inflammation was induced by the following 3 methods: i Hind paw edema was produced by sub plantar injection of 0.1ml of1% carrageenin 3 and paw volume was measured by digital plethysmometer at 0, 3hours. ii Intraperitoneal injection of 1.5% formalin 3 was given to albino mice in peritonitis method and ascitic fluid was measured after 6hours by sacrificing the animals. iii Under ether anesthesia, sterilized &weighed paper discs were implanted subcutaneously in each axilla and groin of male wistar rats sutur ed under sterilized conditions in granuloma 4 method. The discs were cleared of extraneous tissue, dried and weighed on the 5 th day by sacrificing the animals. In all the methods 6 animals in each group (test, standard and control were taken. Results were tabulated in each method separately and statistical analysis was done by student t test. P value < 0.05 considered significant. Percentage inhibition in each method was calculated.

Ethical and Animal Welfare Considerations in Relation to Species Selection for Animal Experimentation

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John Webster

2014-12-01

Full Text Available Ethical principles governing the conduct of experiments with animals are reviewed, especially those relating to the choice of species. Legislation requires that the potential harm to animals arising from any procedure should be assessed in advance and justified in terms of its possible benefit to society. Potential harms may arise both from the procedures and the quality of the animals’ lifetime experience. The conventional approach to species selection is to use animals with the “lowest degree of neurophysiological sensitivity”. However; this concept should be applied with extreme caution in the light of new knowledge. The capacity to experience pain may be similar in mammals, birds and fish. The capacity to suffer from fear is governed more by sentience than cognitive ability, so it cannot be assumed that rodents or farm animals suffer less than dogs or primates. I suggest that it is unethical to base the choice of species for animal experimentation simply on the basis that it will cause less distress within society. A set of responsibilities is outlined for each category of moral agent. These include regulators, operators directly concerned with the conduct of scientific experiments and toxicology trials, veterinarians and animal care staff; and society at large.

Eating frequency, food intake, and weight: a systematic review of human and animal experimental studies

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Hollie eRaynor

2015-12-01

Full Text Available Eating frequently during the day, or grazing, has been proposed to assist with managing food intake and weight. This systematic review assessed the effect of greater eating frequency (EF on intake and anthropometrics in human and animal experimental studies. Studies were identified through the PubMed electronic database. To be included, studies needed to be conducted in controlled settings or use methods that carefully monitored food intake, and measure food intake or anthropometrics. Studies using human or animal models of disease states (i.e., conditions influencing glucose or lipid metabolism, aside from being overweight or obese, were not included. The 25 reviewed studies (15 human and 10 animal studies contained varying study designs, EF manipulations (1 to 24 eating occasions per day, lengths of experimentation (230 min to 28 weeks, and sample sizes (3 to 56 participants/animals per condition. Studies were organized into four categories for reporting results: 1 human studies conducted in laboratory/metabolic ward settings; 2 human studies conducted in field settings; 3 animal studies with experimental periods 1 month. Out of the 13 studies reporting on consumption, 8 (61.5% found no significant effect of EF. Seventeen studies reported on anthropometrics, with 11 studies (64.7% finding no significant effect of EF. Future, adequately powered, studies should examine if other factors (i.e., disease states, physical activity, energy balance and weight status, long-term increased EF influence the relationship between increased EF and intake and/or anthropometrics.

Experimental model of cutaneous radiation injury in rabbits

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Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

2013-07-01

Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

Characterization of experimental dental research using animals

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Ana Flávia Granville-Garcia

2009-01-01

Full Text Available Objective: To determine the profile of experimental dental research using animals. Methods: The research comprised all the 4141 abstracts existent in the books of annals from the 22nd and 23rd Annual meetings of the Brazilian Society of Dentistry Research and the sample was composed of 377 studies (9.1%. The variables analyzed were: area of knowledge, type of institution, State of the country, type of animal and body part used, occurrence of animal sacrifice, mention of the Research Ethics Committee, receipt of funding and type of financing agency. Results: The largest number of studies concentrated on the areas of Buccomaxillofacial Surgery (27.3% and Basic Sciences (21.2%. The Public Universities were responsible for 74% of the researches, and the State Institutions were outstanding (82.4%. The State of São Paulo was responsible for 74.1% of the studies. Rats (67.1% and rabbits (11.1% were the most frequently used animals, and 68.2% of the animals were sacrificed. The oral cavity was used in 50.1% of the researches and the mandible in 59%. Only 1.9% of the studies mentioned the Research Ethics Committee and 26.3% reported that they received funding. Conclusion: In Dentistry, studies involving animals are predominant in the areas of buccomaxillofacial surgery and basic sciences, with rats andrabbits being most frequently used. A significant number of guinea pigs are sacrificed during or at the end of the experiments.

Cardiovascular Imaging: What Have We Learned From Animal Models?

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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.

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

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Daria A Kokova

2017-10-01

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

Experimental model of bladder instability in rabbits

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Balasteghin K.T.

2003-01-01

Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

Understanding in vivo modelling of depression in non-human animals: a systematic review protocol

DEFF Research Database (Denmark)

Bannach-Brown, Alexandra; Liao, Jing; Wegener, Gregers

2016-01-01

experimental model(s) to induce or mimic a depressive-like phenotype. Data that will be extracted include the model or method of induction; species and gender of the animals used; the behavioural, anatomical, electrophysiological, neurochemical or genetic outcome measure(s) used; risk of bias......The aim of this study is to systematically collect all published preclinical non-human animal literature on depression to provide an unbiased overview of existing knowledge. A systematic search will be carried out in PubMed and Embase. Studies will be included if they use non-human animal......-analysis of the preclinical studies modelling depression-like behaviours and phenotypes in animals....

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

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

2016-01-01

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

Using an experimental model for the study of therapeutic touch.

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dos Santos, Daniella Soares; Marta, Ilda Estéfani Ribeiro; Cárnio, Evelin Capellari; de Quadros, Andreza Urba; Cunha, Thiago Mattar; de Carvalho, Emilia Campos

2013-02-01

to verify whether the Paw Edema Model can be used in investigations about the effects of Therapeutic Touch on inflammation by measuring the variables pain, edema and neutrophil migration. this is a pilot and experimental study, involving ten male mice of the same genetic strain and divided into experimental and control group, submitted to the chemical induction of local inflammation in the right back paw. The experimental group received a daily administration of Therapeutic Touch for 15 minutes during three days. the data showed statistically significant differences in the nociceptive threshold and in the paw circumference of the animals from the experimental group on the second day of the experiment. the experiment model involving animals can contribute to study the effects of Therapeutic Touch on inflammation, and adjustments are suggested in the treatment duration, number of sessions and experiment duration.

Animal Models for the Study of Female Sexual Dysfunction

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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

Animal experimentation in forensic sciences: How far have we come?

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Cattaneo, C; Maderna, E; Rendinelli, A; Gibelli, D

2015-09-01

In the third millennium where ethical, ethological and cultural evolution seem to be leading more and more towards an inter-species society, the issue of animal experimentation is a moral dilemma. Speaking from a self-interested human perspective, avoiding all animal testing where human disease and therapy are concerned may be very difficult or even impossible; such testing may not be so easily justifiable when suffering-or killing-of non human animals is inflicted for forensic research. In order to verify how forensic scientists are evolving in this ethical issue, we undertook a systematic review of the current literature. We investigated the frequency of animal experimentation in forensic studies in the past 15 years and trends in publication in the main forensic science journals. Types of species, lesions inflicted, manner of sedation or anesthesia and euthanasia were examined in a total of 404 articles reviewed, among which 279 (69.1%) concerned studies involving animals sacrificed exclusively for the sake of the experiment. Killing still frequently includes painful methods such as blunt trauma, electrocution, mechanical asphyxia, hypothermia, and even exsanguination; of all these animals, apparently only 60.8% were anesthetized. The most recent call for a severe reduction if not a total halt to the use of animals in forensic sciences was made by Bernard Knight in 1992. In fact the principle of reduction and replacement, frequently respected in clinical research, must be considered the basis for forensic science research needing animals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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

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

2012-01-01

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

Science and society: different bioethical approaches towards animal experimentation.

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Brom, Frans W A

2002-01-01

respect their integrity. By weighing these prima facie duties, the moral problem of animal experimentation exists in finding which duty actually has to be considered as the decisive duty. It will be argued that these three views, even though they will all justify animal experimentation to some extent, will do so in practice under different conditions. Many current conflicts regarding the use of animals for research may be better understood in light of the conflict between the three bioethical perspectives provided by these views.

Experimental evidence for inherent Lévy search behaviour in foraging animals.

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Kölzsch, Andrea; Alzate, Adriana; Bartumeus, Frederic; de Jager, Monique; Weerman, Ellen J; Hengeveld, Geerten M; Naguib, Marc; Nolet, Bart A; van de Koppel, Johan

2015-05-22

Recently, Lévy walks have been put forward as a new paradigm for animal search and many cases have been made for its presence in nature. However, it remains debated whether Lévy walks are an inherent behavioural strategy or emerge from the animal reacting to its habitat. Here, we demonstrate signatures of Lévy behaviour in the search movement of mud snails (Hydrobia ulvae) based on a novel, direct assessment of movement properties in an experimental set-up using different food distributions. Our experimental data uncovered clusters of small movement steps alternating with long moves independent of food encounter and landscape complexity. Moreover, size distributions of these clusters followed truncated power laws. These two findings are characteristic signatures of mechanisms underlying inherent Lévy-like movement. Thus, our study provides clear experimental evidence that such multi-scale movement is an inherent behaviour rather than resulting from the animal interacting with its environment. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Animal models of tinnitus.

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Brozoski, Thomas J; Bauer, Carol A

2016-08-01

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

Surface Simplification of 3D Animation Models Using Robust Homogeneous Coordinate Transformation

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Juin-Ling Tseng

2014-01-01

Full Text Available The goal of 3D surface simplification is to reduce the storage cost of 3D models. A 3D animation model typically consists of several 3D models. Therefore, to ensure that animation models are realistic, numerous triangles are often required. However, animation models that have a high storage cost have a substantial computational cost. Hence, surface simplification methods are adopted to reduce the number of triangles and computational cost of 3D models. Quadric error metrics (QEM has recently been identified as one of the most effective methods for simplifying static models. To simplify animation models by using QEM, Mohr and Gleicher summed the QEM of all frames. However, homogeneous coordinate problems cannot be considered completely by using QEM. To resolve this problem, this paper proposes a robust homogeneous coordinate transformation that improves the animation simplification method proposed by Mohr and Gleicher. In this study, the root mean square errors of the proposed method were compared with those of the method proposed by Mohr and Gleicher, and the experimental results indicated that the proposed approach can preserve more contour features than Mohr’s method can at the same simplification ratio.

[Advances in animal model and traditional Chinese medicine prevention in coronary microvascular dysfunction].

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Li, Lei; Liu, Jian-Xun; Ren, Jian-Xun; Guo, Hao; Lin, Cheng-Ren

2017-01-01

Coronary microvascular dysfunction (CMD) is a common mechanism for some heart disease like cardiac X syndrome and no-reflow phenomenon after percutaneous coronary intervention(PCI). With the development of medical imageology, CMD has received increased attention. Animal model of CMD is indispensable tool for the research of pathogenesis and treatment evaluation, therefor choose an appropriate animal model is the first issue to carry out CMD research. Experimental and clinical studies have shown unique effectiveness of traditional Chinese medicine(TCM) in CMD therapy. Clarifying of the TCM therapeutic effect mechanisms and seeking an optimal solution of combination of traditional Chinese and western medicine will be the focus of future research. This paper reviewed the establishment and evaluation of CMD animal model, as well as the intervention study of TCM on CMD. The article aims to provide reference for the basic research of CMD and the TCM experimental study on CMD. Copyright© by the Chinese Pharmaceutical Association.

[Animal experimental study of compression anastomosis ring for low anterior resection].

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Liang, Jian-Wei; Wang, Zheng; Zhang, Xing-Mao; Zhan, Da-Wei; Zhou, Zhi-Xiang

2011-05-01

To evaluate the feasibility and safety of nickel-titanium compression anastomosis ring (CAR27) in colorectal anastomosis after low anterior rectal resection in animal models. End-to-end colorectal anastomosis was performed using CAR27 in 6 experimental pigs after resection of the middle and lower third of the rectum. The animals were observed postoperatively for up to 56 days. Five pigs were sacrificed at day 14 and the other at day 56. Distance from anal verge to anastomosis and anastomotic circumference were measured. Histopathologic examination was performed. The median distance from anal verge was 5.3(4-6) cm. No anastomotic leak or other complications were observed. All the pigs recovered and gained weight. In 5 animals sacrificed at day 14, the mean circumference of the anastomosis was 6.8(6.5-7.0) cm, and histopathological examination showed mild inflammatory reaction and fibrosis. In the one sacrificed at day 56, the circumference expanded to 9.3 cm, and no inflammation and fibrosis were observed. Minor adhesion was noticed in only one pig, while smooth and intact serosa in the anastomosis was seen in the rest of the animals. CAR27 is a promising device for mid and low colorectal anastomosis.

Domestic Pig (Sus scrofa) as an Animal Model for Experimental Trypanosoma cruzi Infection

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Yauri, Verónica; Castro-Sesquen, Yagahira E.; Verastegui, Manuela; Angulo, Noelia; Recuenco, Fernando; Cabello, Ines; Malaga, Edith; Bern, Caryn; Gavidia, Cesar M.; Gilman, Robert H.

2016-01-01

Pigs were infected with a Bolivian strain of Trypanosoma cruzi (genotype I) and evaluated up to 150 days postinoculation (dpi) to determine the use of pigs as an animal model of Chagas disease. Parasitemia was observed in the infected pigs during the acute phase (15–40 dpi). Anti-T.cruzi immunoglobulin M was detected during 15–75 dpi; high levels of anti-T.cruzi immunoglobulin G were detected in all infected pigs from 75 to 150 dpi. Parasitic DNA was observed by western blot (58%, 28/48) and polymerase chain reaction (27%, 13/48) in urine samples, and in the brain (75%, 3/4), spleen (50%, 2/4), and duodenum (25%, 1/4), but no parasitic DNA was found in the heart, colon, and kidney. Parasites were not observed microscopically in tissues samples, but mild inflammation, vasculitis, and congestion was observed in heart, brain, kidney, and spleen. This pig model was useful for the standardization of the urine test because of the higher volume that can be obtained as compared with other small animal models. However, further experiments are required to observe pathological changes characteristic of Chagas disease in humans. PMID:26928841

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.

Study Design Rigor in Animal-Experimental Research Published in Anesthesia Journals.

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Hoerauf, Janine M; Moss, Angela F; Fernandez-Bustamante, Ana; Bartels, Karsten

2018-01-01

Lack of reproducibility of preclinical studies has been identified as an impediment for translation of basic mechanistic research into effective clinical therapies. Indeed, the National Institutes of Health has revised its grant application process to require more rigorous study design, including sample size calculations, blinding procedures, and randomization steps. We hypothesized that the reporting of such metrics of study design rigor has increased over time for animal-experimental research published in anesthesia journals. PubMed was searched for animal-experimental studies published in 2005, 2010, and 2015 in primarily English-language anesthesia journals. A total of 1466 publications were graded on the performance of sample size estimation, randomization, and blinding. Cochran-Armitage test was used to assess linear trends over time for the primary outcome of whether or not a metric was reported. Interrater agreement for each of the 3 metrics (power, randomization, and blinding) was assessed using the weighted κ coefficient in a 10% random sample of articles rerated by a second investigator blinded to the ratings of the first investigator. A total of 1466 manuscripts were analyzed. Reporting for all 3 metrics of experimental design rigor increased over time (2005 to 2010 to 2015): for power analysis, from 5% (27/516), to 12% (59/485), to 17% (77/465); for randomization, from 41% (213/516), to 50% (243/485), to 54% (253/465); and for blinding, from 26% (135/516), to 38% (186/485), to 47% (217/465). The weighted κ coefficients and 98.3% confidence interval indicate almost perfect agreement between the 2 raters beyond that which occurs by chance alone (power, 0.93 [0.85, 1.0], randomization, 0.91 [0.85, 0.98], and blinding, 0.90 [0.84, 0.96]). Our hypothesis that reported metrics of rigor in animal-experimental studies in anesthesia journals have increased during the past decade was confirmed. More consistent reporting, or explicit justification for absence

Sleep and Obesity: A focus on animal models

Science.gov (United States)

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

2012-01-01

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

Optimizing laboratory animal stress paradigms: The H-H* experimental design.

Science.gov (United States)

McCarty, Richard

2017-01-01

Major advances in behavioral neuroscience have been facilitated by the development of consistent and highly reproducible experimental paradigms that have been widely adopted. In contrast, many different experimental approaches have been employed to expose laboratory mice and rats to acute versus chronic intermittent stress. An argument is advanced in this review that more consistent approaches to the design of chronic intermittent stress experiments would provide greater reproducibility of results across laboratories and greater reliability relating to various neural, endocrine, immune, genetic, and behavioral adaptations. As an example, the H-H* experimental design incorporates control, homotypic (H), and heterotypic (H*) groups and allows for comparisons across groups, where each animal is exposed to the same stressor, but that stressor has vastly different biological and behavioral effects depending upon each animal's prior stress history. Implementation of the H-H* experimental paradigm makes possible a delineation of transcriptional changes and neural, endocrine, and immune pathways that are activated in precisely defined stressor contexts. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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Cekanova M

2014-10-01

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

Transvaginal ultrasound ovarian diathermy: sheep as an experimental model

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Pimentel Anita M

2012-01-01

Full Text Available Abstract Background Some techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model. Findings An experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale and 3.41 cm2 ± 0,64 (Suffolk. From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path. Conclusions This is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.

Life sciences research in space: The requirement for animal models

Science.gov (United States)

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

1987-01-01

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

Animal Models in Burn Research

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

2014-01-01

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

Are animal models predictive for human postmortem muscle protein degradation?

Science.gov (United States)

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

2017-11-01

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

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

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.

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

Directory of Open Access Journals (Sweden)

Tian Y

2016-04-01

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

Animal models of cerebral ischemia

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

2015-11-01

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

Experimental models of chronic subdural hematoma.

Science.gov (United States)

D'Abbondanza, Josephine A; Loch Macdonald, R

2014-02-01

Chronic subdural hematoma (CSDH) is a common neurosurgical problem. Most studies of pathogenesis and treatment involve humans. Advances in understanding of human diseases may be made using animal models. We reviewed all animal models of CSDH and report here their results, conclusions and limitations in order to set a baseline upon which further advanced experimental work related to this disease can be made. PubMed, Medline, Embase and ISI Web of Knowledge were searched with no time limits using the keyword 'chronic subdural hematoma' and MeSH term 'hematoma, subdural, chronic'. The authors reviewed all papers written related to this disease and selected all publications involving animals. There were no other restrictions. The findings and conclusions of the papers are summarized here. No formal analysis was done because of the variation in species used, methods for induction of CSDH, times of assessment and reporting of results. Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description. We did not find a report of a reproducible, well-described animal model of human CSDH.

Discussion on the establishment of blood glucose fluctuation animal models

OpenAIRE

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

2014-01-01

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

Biological effects of transuranium elements in experimental animals

International Nuclear Information System (INIS)

Bair, W.J.

1975-01-01

Results are reported from life span studies of the biological effects of the transuranium elements ( 238 Pu, 239 Pu, 241 Am, and 242 Cm) on laboratory animals following inhalation, skin absorption, or injection in various chemical forms. The dose levels at which major biological effects have been observed in experimental animals are discussed relative to the maximum permissible lung burden of 0.016 μCi for occupational exposures. Lung cancer has been observed at dose levels equivalent to about 100 times the maximum permissible lung burden. Current experiments directed towards determining whether health effects will occur at lower levels and the mechanisms by which α emitters induce cancer are reviewed. (U.S.)

[Change of blood antioxidant capacity of experimental animals during nutritional correction under oxidative stress].

Science.gov (United States)

Basov, A A; Bykov, I M

2013-01-01

The effect of nutritional correction (a diet high in foods with antioxidant content) on blood parameters in laboratory animals with metabolic disorders associated with oxidative stress has been studied. In experimental models of laboratory animals (male rabbits weighing 3.5-4.0 kg, n = 40) with purulent septic diseases it has been demonstrated that the use of nutritive correction (replacement of 100 g of the cereal mixture through day on a mixture of cabbage 50 g, carrots 50 g, beet 25 g, apple 25 g, kiwi 10 g and garnet 10 g per 1 rabbit) is not inferior to its efficiency of glutathione use (2 g per day). The use of these antioxidants in laboratory animals significantly reduced the phenomenon of oxidative stress on the 5th day: blood antioxidant capacity significantly increased by 14.9 and 26.6%, and the area of the flash of luminol-dependent H2O2-induced chemiluminescence of blood plasma reduced by 44.2 and 48.6% in the experimental groups receiving respectively nutritive correction and glutathione. The low-molecula level of blood antioxidant capacity was restored and the balance of the activity of superoxide dismutase (decrease) and catalase (increase) was achieved on the 10th day of the experiment. These figures significantly (p < 0.05) differed from than in the group of animals receiving no antioxidant correction. The latter studied parameters of prooxidant-antioxidant system reached values comparable with those in intact animals (n = 10) only on the 30th day, confirming the advisability of appointing a complex antioxidant therapy.

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

OpenAIRE

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

2002-01-01

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

Maternal hypothyroidism: An overview of current experimental models.

Science.gov (United States)

Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-10-15

Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use

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Schneider Erich

2007-08-01

Full Text Available Abstract Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation in concert with the AO Research Institute (ARI, and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1 Intelligent study designs to receive appropriate answers; 2 Minimal complication rates (5 to max. 10%; 3 Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA audit of protocols in GLP studies; 4 Sufficient details for materials and methods applied; 5 Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences; 6 Post-operative management with emphasis on analgesia and follow-up examinations; 7 Study protocols to satisfy criteria established for a "justified animal study"; 8 Surgical expertise to conduct surgery on animals; 9 Pilot studies as a critical part of model validation and powering of the definitive study design

Implant healing in experimental animal models of diabetes.

Science.gov (United States)

Le, Nga N; Rose, Michael B; Levinson, Howard; Klitzman, Bruce

2011-05-01

influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices. © 2011 Diabetes Technology Society.

Anorexia in human and experimental animal models: physiological aspects related to neuropeptides.

Science.gov (United States)

Yoshimura, Mitsuhiro; Uezono, Yasuhito; Ueta, Yoichi

2015-09-01

Anorexia, a loss of appetite for food, can be caused by various physiological and pathophysiological conditions. In this review, firstly, clinical aspects of anorexia nervosa are summarized in brief. Secondly, hypothalamic neuropeptides responsible for feeding regulation in each hypothalamic nucleus are discussed. Finally, three different types of anorexigenic animal models; dehydration-induced anorexia, cisplatin-induced anorexia and cancer anorexia-cachexia, are introduced. In conclusion, hypothalamic neuropeptides may give us novel insight to understand and find effective therapeutics strategy essential for various kinds of anorexia.

[For active dermatocosmetics and free of unnecessary animal experimentation].

Science.gov (United States)

Piérard, G E; Piérard-Franchimont, C

1998-06-01

At the dawn of this century, dermocosmetology is at cross-roads because new European regulations are changing its face. The proof of claims must be given and the entire composition of the product must be released. In addition, animal testing is about to be banned. Such new regulations incite to search for and validate predictive tests aiming at the objective evaluation of the activity and tolerance claimed by dermocosmetic products. Such tests must be an alternative to unnecessary animal experimentation. These aspects are scrutinized scientifically by the EEMCO experts in combination with the ECVAM and COLIPA organizations.

ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

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Elsy Nalleli Loria-Cervera

2014-01-01

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

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

Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

DEFF Research Database (Denmark)

Kloster, Brian Ozeraitis; Lund, Lars; Lindholt, Jes S.

2015-01-01

BackgroundA large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. Methods10 pigs...

Plant G-Proteins Come of Age: Breaking the Bond with Animal Models.

Science.gov (United States)

Trusov, Yuri; Botella, José R

2016-01-01

G-proteins are universal signal transducers mediating many cellular responses. Plant G-protein signaling has been modeled on the well-established animal paradigm but accumulated experimental evidence indicates that G-protein-dependent signaling in plants has taken a very different evolutionary path. Here we review the differences between plant and animal G-proteins reported over past two decades. Most importantly, while in animal systems the G-protein signaling cycle is activated by seven transmembrane-spanning G-protein coupled receptors, the existence of these type of receptors in plants is highly controversial. Instead plant G-proteins have been proven to be functionally associated with atypical receptors such as the Arabidopsis RGS1 and a number of receptor-like kinases. We propose that, instead of the GTP/GDP cycle used in animals, plant G-proteins are activated/de-activated by phosphorylation/de-phosphorylation. We discuss the need of a fresh new look at these signaling molecules and provide a hypothetical model that departs from the accepted animal paradigm.

Neuroprotective properties of curcumin in toxin-base animal models of Parkinson's disease: a systematic experiment literatures review.

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Wang, Xin-Shi; Zhang, Zeng-Rui; Zhang, Man-Man; Sun, Miao-Xuan; Wang, Wen-Wen; Xie, Cheng-Long

2017-08-17

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective actions of curcumin have been documented for experimental therapy in Parkinson's disease (PD). In this study, we used a systematic review to comprehensively assess the efficacy of curcumin in experimental PD. Using electronic and manual search for the literatures, we identified studies describing the efficacy of curcumin in animal models of PD. We identified 13 studies with a total of 298 animals describing the efficacy of curcumin in animal models of PD. The methodological quality of all preclinical trials is ranged from 2 to 5. The majority of the experiment studies demonstrated that curcumin was more significantly neuroprotection effective than control groups for treating PD. Among them, five studies indicated that curcumin had an anti-inflammatory effect in the PD animal models (p curcumin, by which it protected substantia nigra neurons and improved striatal dopamine levels. Furthermore, two studies in this review displayed that curcumin treatment was also effective in reducing neuronal apoptosis and improving functional outcome in animal models of PD. Most of the preclinical studies demonstrated the positive findings while one study reported that curcumin had no beneficial effects against Mn-induced disruption of hippocampal metal and neurotransmitter homeostasis. The results demonstrated a marked efficacy of curcumin in experimental model of PD, suggesting curcumin probably a candidate neuroprotective drug for human PD patients.

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

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

2015-01-01

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

A novel animal model of dysphagia following stroke.

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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.

Comparative studies on the ossification in several experimental animals

International Nuclear Information System (INIS)

Matsuoka, Osamu; Fukuda, Shun

1978-01-01

For estimating the risk of the bone seeking radionuclides in man, it is necessary to extrapolate the data of experimental animals to those of man. Detailed information on the biological stages of development, especially on bone growth of several experimental animals and of man is required for better extrapolation. Multi-species comparison of bone growth and ossification was carried out in several mammalian species such as mouse, rat, dog and monkey. The appearance, ossifying process and fusion of the secondary ossification centers in extremities were selected as indicators of the biological stage of bone. The observation of the secondary ossification centers was made by radiography. The maturity process of the secondary ossification centers in each animal was illustrated. The ossifying process of the secondary ossification center could be divided into the following three categories; (1) the acute ossification observed in mouse, rat, dog and monkey (2) the delayed ossification observed in mouse, rat, dog and monkey, (3) the incomplete ossification without complete fusion which is specific in mouse and rat, appeared and continued up to at least 27 weeks in mouse and up to 134 weeks in rat. The results of the study suggested that a mouse 17 weeks old, a rat 17 - 21 weeks old, a dog (beagle) 14 months old and a monkey about 6 years old may correspond to a man about 20 years old. (author)

The Animal Experimentation Controversy: Ethical Views of Prospective Teachers

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de Villiers, Rian

2012-01-01

Vivisection (live animal experimentation) is a controversial issue for many people. The purpose of this case study is to examine the attitudes of prospective teachers toward vivisection in education and research, to determine if gender has an influence on these attitudes, and to discuss the implications of these attitudes with regard to teaching…

Animal Models for Periodontal Disease

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Helieh S. Oz

2011-01-01

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

Animal Models for Periodontal Disease

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Oz, Helieh S.; Puleo, David A.

2011-01-01

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

Evaluation of animal models of neurobehavioral disorders

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Nordquist Rebecca E

2009-02-01

Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

Animal models.

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Walker, Ellen A

2010-01-01

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

Diagnosis of abdominal abscess: A large animal model

International Nuclear Information System (INIS)

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

1988-01-01

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

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

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Dutta, Sarmistha; Das, Swarnamoni

2010-01-01

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

Ethical issues associated with the use of animal experimentation in behavioral neuroscience research.

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Ohl, Frauke; Meijboom, Franck

2015-01-01

This chapter briefly explores whether there are distinct characteristics in the field of Behavioral Neuroscience that demand specific ethical reflection. We argue that although the ethical issues in animal-based Behavioral Neuroscience are not necessarily distinct from those in other research disciplines using animal experimentation, this field of endeavor makes a number of specific, ethically relevant, questions more explicit and, as a result, may expose to discussion a series of ethical issues that have relevance beyond this field of science. We suggest that innovative research, by its very definition, demands out-of-the-box thinking. At the same time, standardization of animal models and test procedures for the sake of comparability across experiments inhibits the potential and willingness to leave well-established tracks of thinking, and leaves us wondering how open minded research is and whether it is the researcher's established perspective that drives the research rather than the research that drives the researcher's perspective. The chapter finishes by introducing subsequent chapters of this book volume on Ethical Issues in Behavioral Neuroscience.

Potency of Animal Models in KANSEI Engineering

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Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

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

Associating Animations with Concrete Models to Enhance Students' Comprehension of Different Visual Representations in Organic Chemistry

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Al-Balushi, Sulaiman M.; Al-Hajri, Sheikha H.

2014-01-01

The purpose of the current study is to explore the impact of associating animations with concrete models on eleventh-grade students' comprehension of different visual representations in organic chemistry. The study used a post-test control group quasi-experimental design. The experimental group (N = 28) used concrete models, submicroscopic…

An animal model for tinnitus.

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

1988-03-01

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

A micro-PET/CT approach using O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine in an experimental animal model of F98 glioma for BNCT

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Menichetti, L., E-mail: luca.menichetti@ifc.cnr.it [CNR Institute of Clinical Physiology, Pisa (Italy); Petroni, D.; Panetta, D. [CNR Institute of Clinical Physiology, Pisa (Italy); Burchielli, S. [Fondazione CNR/Regione Toscana G. Monasterio, Pisa (Italy); Bortolussi, Silva [Dept. Theoretical and Nuclear Physics, University of Pavia, Pavia (Italy); Matteucci, M. [Scuola Superiore Sant' Anna, Pisa (Italy); Pascali, G.; Del Turco, S. [CNR Institute of Clinical Physiology, Pisa (Italy); Del Guerra, A. [Department of Physics, University of Pisa, Pisa (Italy); Altieri, S. [Dept. Theoretical and Nuclear Physics, University of Pavia, Pavia (Italy); Salvadori, P.A. [CNR Institute of Clinical Physiology, Pisa (Italy)

2011-12-15

The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that {sup 18}F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and {alpha}-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.

Comparative systems biology between human and animal models based on next-generation sequencing methods.

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Zhao, Yu-Qi; Li, Gong-Hua; Huang, Jing-Fei

2013-04-01

Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

Experimental models of sepsis and septic shock: an overview

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Garrido Alejandra G.

2004-01-01

Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

[F18]-FDG imaging of experimental animal tumours using a hybrid gamma-camera

International Nuclear Information System (INIS)

Lausson, S.; Maurel, G.; Kerrou, K.; Montravers, F.; Petegnief, Y.; Talbot, J.N.; Fredelizi, D.

2001-01-01

Positron emission tomography (PET) has been widely used in clinical studies. This technology permits detection of compounds labelled with positron emitting radionuclides and in particular, [F18]-fluorodeoxyglucose ([F18]-FDG).[F18]-FDG uptake and accumulation is generally related to malignancy; some recent works have suggested the usefulness of PET camera dedicated to small laboratory animals (micro-PET). Our study dealt with the feasibility of [F18]-FDG imaging of malignant tumours in animal models by means of an hybrid camera dedicated for human scintigraphy. We evaluated the ability of coincidence detection emission tomography (CDET) using this hybrid camera to visualize in vivo subcutaneous tumours grafted to mice or rats. P815 murine mastocytoma grafted in syngeneic DBA/2 mice resulted with foci of very high FDG uptake. Tumours with a diameter of only 3 mm were clearly visualized. Medullary thyroid cancer provoked by rMTC 6/23 and CA77 lines in syngeneic Wag/Rij rat was also detected. The differentiated CA77 tumours exhibited avidity for [F18]-FDG and a tumour, which was just palpable (diameter lower than 2 mm), was identified. In conclusion, CDET-FDG is a non-invasive imaging tool which can be used to follow grafted tumours in the small laboratory animal, even when their size is smaller than 1 cm. It has the potential to evaluate experimental anticancer treatments in small series of animals by individual follow-up. It offers the opportunity to develop experimental PET research within a nuclear medicine or biophysics department, the shift to a dedicated micro-PET device being subsequently necessary. It is indeed compulsory to strictly follow the rules for non contamination and disinfection of the hybrid camera. (authors)

Effects of experimental sleep deprivation on anxiety-like behavior in animal research: Systematic review and meta-analysis.

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Pires, Gabriel Natan; Bezerra, Andréia Gomes; Tufik, Sergio; Andersen, Monica Levy

2016-09-01

Increased acute anxiety is a commonly reported behavioral consequence of sleep deprivation in humans. However, rodent studies conducted so far produced inconsistent results, failing to reproduce the same sleep deprivation induced-anxiety observed in clinical experiments. While some presented anxiogenesis as result of sleep deprivation, others reported anxiolysis. In face of such inconsistencies, this article explores the effects of experimental sleep deprivation on anxiety-like behavior in animal research through a systematic review and a series of meta-analyses. A total of 50 of articles met our inclusion criteria, 30 on mice, 19 on rats and one on Zebrafish. Our review shows that sleep deprivation induces a decrease in anxiety-like behavior in preclinical models, which is opposite to results observed in human settings. These results were corroborated in stratified analyses according to species, sleep deprivation method and anxiety measurement technique. In conclusion, the use of animal models for the evaluation of the relationship between sleep deprivation lacks translational applicability and new experimental tools are needed to properly evaluate sleep deprivation-induced anxiogenesis in rodents. Copyright © 2016 Elsevier Ltd. All rights reserved.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

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Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

2006-01-01

Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Result...

Panel 4: Recent Advances in Otitis Media in Molecular Biology, Biochemistry, Genetics, and Animal Models

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Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F.; Bakaletz, Lauren O.; Brown, Steve D.; Cheeseman, Michael T.; Juhn, Steven K.; Jung, Timothy T. K.; Lim, David J.; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J. Christopher

2014-01-01

Background Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications. PMID:23536532

Animal models for rotator cuff repair.

Science.gov (United States)

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

2016-11-01

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

Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism.

Science.gov (United States)

Kim, Ji-Woon; Seung, Hana; Kim, Ki Chan; Gonzales, Edson Luck T; Oh, Hyun Ah; Yang, Sung Min; Ko, Mee Jung; Han, Seol-Heui; Banerjee, Sourav; Shin, Chan Young

2017-02-01

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Principles of animal extrapolation

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Calabrese, E.J.

1991-01-01

Animal Extrapolation presents a comprehensive examination of the scientific issues involved in extrapolating results of animal experiments to human response. This text attempts to present a comprehensive synthesis and analysis of the host of biomedical and toxicological studies of interspecies extrapolation. Calabrese's work presents not only the conceptual basis of interspecies extrapolation, but also illustrates how these principles may be better used in selection of animal experimentation models and in the interpretation of animal experimental results. The book's theme centers around four types of extrapolation: (1) from average animal model to the average human; (2) from small animals to large ones; (3) from high-risk animal to the high risk human; and (4) from high doses of exposure to lower, more realistic, doses. Calabrese attacks the issues of interspecies extrapolation by dealing individually with the factors which contribute to interspecies variability: differences in absorption, intestinal flora, tissue distribution, metabolism, repair mechanisms, and excretion. From this foundation, Calabrese then discusses the heterogeneticity of these same factors in the human population in an attempt to evaluate the representativeness of various animal models in light of interindividual variations. In addition to discussing the question of suitable animal models for specific high-risk groups and specific toxicological endpoints, the author also examines extrapolation questions related to the use of short-term tests to predict long-term human carcinogenicity and birth defects. The book is comprehensive in scope and specific in detail; for those environmental health professions seeking to understand the toxicological models which underlay health risk assessments, Animal Extrapolation is a valuable information source.

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

Directory of Open Access Journals (Sweden)

Iwona Piotrowska

2014-06-01

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

How does sex matter? Behavior, stress and animal models of neurobehavioral disorders.

Science.gov (United States)

Palanza, Paola; Parmigiani, Stefano

2017-05-01

Many aspects of brain functioning exhibit important sex differences that affect behavior, mental health and mental disorders. However, most translational neuroscience research related to animal models of neurobehavioral disorders are carried out in male animals only. Based on published data from our laboratory on the House mouse, we discuss the following issues: (1) sex differences in social behavior of wild-derived mice; (2) artificial selection of laboratory strains and its consequences on social and reproductive competition; (3) sex-dependent effects of common experimental procedures; (4) differential effects of developmental events: the case of endocrine disruption; (5) implications for female models of stress and neurobehavioral disorders. Altogether, this review of data outline the marked differences of male and female responses to different social challenges and evinces the current lack of a relevant female mouse model of social stress. Whilst animal modelling is an important approach towards understanding mechanisms of neurobehavioral disorders, it is evident that data obtained in males may be irrelevant for inferring psychopathology and efficacy of pharmacological treatments for females. Copyright © 2017 Elsevier Ltd. All rights reserved.

Following the genes: a framework for animal modeling of psychiatric disorders

LENUS (Irish Health Repository)

Mitchell, Kevin

2011-11-11

Abstract The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans.

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

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Kiss, Ana Ci; Lima, Paula Ho; Sinzato, Yuri K; Takaku, Mariana; Takeno, Marisa A; Rudge, Marilza Vc; Damasceno, Débora C

2009-10-19

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. 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. 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. Experimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women

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

Directory of Open Access Journals (Sweden)

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

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

Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

Science.gov (United States)

Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

2017-04-01

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ɛ-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.

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Gutowski, Michal B; Wilson, Leslie; Van Gelder, Russell N; Pepple, Kathryn L

2017-03-01

We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

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

Science.gov (United States)

Sonnenfeld, Gerald

2005-01-01

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

Evaluation of agents to detect inflammatory foci using an experimental animal model

International Nuclear Information System (INIS)

Shimpi, H.H.; Noronha, O.P.D.; Samuel, A.M.

1997-01-01

We have evaluated the propensities of four agents- two metal complexes and two protein species, viz. 67 Ga-citrate, 99m Tc-citrate, 99m Tc-human immunoglobulin ( 99m Tc-HIG); and 99m Tc-human serum albumin ( 99m Tc-HSA), for localization of (turpentine- induced) inflammatory lesions in a rat and rabbit animal model systems. All these radiopharmaceuticals showed fairly good uptake in inflammatory lesions. 99m Tc-HIG, 99m Tc-HSA and 67 Ga-citrate showed slower blood clearance and higher liver uptakes. On the other hand 99m Tc-citrate demonstrated faster blood clearance and negligible liver and gut accumulation. The respective inflamed/normal muscle (IM/NM) ratios obtained with these agents in this animal model were in the following order: 99m Tc-HIG> 99m Tc-HSA> 67 Ga-citrate> 99m Tc-citrate at 5 h post injection. Although the IM/NM was relatively low in the case of 99m Tc-citrate as compared with other radiopharmaceuticals the inflammation could be detected within 1-3 h. post injection because of the higher activities that could be injected with this radiopharmaceutical. Since 99m Tc-citrate is predominantly excreted via renal pathway it is rapidly cleared from blood and shows fairly good accumulation in infection/inflammatory lesions at early time periods along with low uptakes in liver and adjacent organs. This agent can therefore be beneficially used to detect the abdominal abscess(es)/inflammation(s) within 1-3 h post injection. Because of its favourable characteristics, physical, biological, clinical, and even cost-effectiveness, it is suggested that 99m Tc-citrate could be tried out as an agent for detection of inflammation including abdominal and vertebral abscess(es). (author)

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.

Animal Models of Calcific Aortic Valve Disease

Directory of Open Access Journals (Sweden)

Krista L. Sider

2011-01-01

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

An experimental model of mycobacterial infection under corneal flaps

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C.B.D. Adan

2004-07-01

Full Text Available In order to develop a new experimental animal model of infection with Mycobacterium chelonae in keratomileusis, we conducted a double-blind prospective study on 24 adult male New Zealand rabbits. One eye of each rabbit was submitted to automatic lamellar keratotomy with the automatic corneal shaper under general anesthesia. Eyes were immunosuppressed by a single local injection of methyl prednisolone. Twelve animals were inoculated into the keratomileusis interface with 1 µl of 10(6 heat-inactivated bacteria (heat-inactivated inoculum controls and 12 with 1 µl of 10(6 live bacteria. Trimethoprim drops (0.1%, w/v were used as prophylaxis for the surgical procedure every 4 h (50 µl, qid. Animals were examined by 2 observers under a slit lamp on the 1st, 3rd, 5th, 7th, 11th, 16th, and 23rd postoperative days. Slit lamp photographs were taken to document clinical signs. Animals were sacrificed when corneal disease was detected and corneal samples were taken for microbiological analysis. Eleven of 12 experimental rabbits developed corneal disease, and M. chelonae could be isolated from nine rabbits. Eleven of the 12 controls receiving a heat-inactivated inoculum did not develop corneal disease. M. chelonae was not isolated from any of the control rabbits receiving a heat-inactivated inoculum, or from the healthy cornea of control rabbits. Corneal infection by M. chelonae was successfully induced in rabbits submitted to keratomileusis. To our knowledge, this is the first animal model of M. chelonae infection following corneal flaps for refractive surgery to be described in the literature and can be used for the analysis of therapeutic responses.

Animal models of attention-deficit hyperactivity disorder

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Sagvolden Terje

2005-07-01

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

Animal models for investigating chronic pancreatitis

Science.gov (United States)

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

[Christian responsibility and experimental medicine. Experiments with and on humans, experiments on animals].

Science.gov (United States)

Grosse, Heinrich W

2002-01-01

The Jewish-Christian convictions that man was created as the image of God founded the "ethics of unavailability" which contrast with the utilitarian "ethics of interests." As man s nature is imperfect according to biblical understanding, those responsible in the field of experimental medicine should counteract all tendencies in society which promote an utopian definition of health and an eugenic mentality (idea of the "perfection of mankind"). Consequently, scientists must reflect their own image of man and the effects of their actions on this image. The goals of experimental medicine must also be examined under the aspect of fairness: do they only benefit a minority in the rich industrial nations? As in research on humans, the ethical evaluation of animal experiments must consider the question of the underlying image of humanity and the responsibility of mankind connected to it. Because of changes in society's values, the validity of traditional anthropocentrism is increasingly questioned. However, this does not affect the view of the special position of man as the bearer of responsibility. Even though there are different biblical statements on the relationship between man and animal, the Christian maxim to minimise violence towards animals can be derived from them. In the case of animal experiments this means: experiments which cause the animals severe suffering must be avoided by waiving the potential gain of knowledge from them. In general: in an ethical discussion on medical experiments using humans or animals, the public must be informed completely and involved effectively. A moratorium must be possible before plans become facts. Thinking about ethical problems in the area of experimental medicine should not be separated from the far-reaching questions about changes in our lifestyle and consumer behaviour.

[Experimental model of severe local radiation injuries of the skin after X-rays].

Science.gov (United States)

Kotenko, K V; Moroz, B B; Nasonova, T A; Dobrynina, O A; LIpengolz, A A; Gimadova, T I; Deshevoy, Yu B; Lebedev, V G; Lyrschikova, A V; Eremin, I I

2013-01-01

The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

Checklist of vertebrate animals of the Cascade Head Experimental Forest.

Science.gov (United States)

Chris Maser; Jerry F. Franklin

1974-01-01

Three months, April and August 1971 and August 1972, were spent studying the vertebrate fauna of Cascade Head Experimental Forest. The resulting annotated checklist includes 9 amphibians, 2 reptiles, 35 birds, and 40 mammals. A standardized animal habitat classification is presented in an effort to correlate the vertebrates in some meaningful way to their environment...

[Origin of animal experimentation legislation in the 19th century].

Science.gov (United States)

Pocard, M

1999-01-01

The first legislation in the world, designed to protect animals used in research, was passed in England in 1876, and is still in force today. It is one of the strictest in Europe. At the same period, France had no such law, and was the country conducting the greatest amount of animal experimentation. Comparing, these two countries, in the middle of the 19th century, can account for this difference. The most important difference seems to be related to the theological question: are animals endowed with a soul? Saint Augustine, claimed, in the 4th century, perhaps because of an experiment with the centipede, that animals do not have a soul. In the 17th century, René Descartes, using a different philosophical system, reached a similar conclusion, in France. On the other hand, under the influence of Charles Darwin, England rejected the Roman Catholic conclusion, about the soul of animals. The industrial revolution, occurring earlier in England than in France, also changed the society, developing urban areas, where people were cut off from rural life and changing human relationships with animals. The industrial revolution enabled the development of the press, giving impetus to public opinion. These facts, combined with a caution of science, which was more developed in England than in France, brought about the first important "anti-doctor" campaign.

Grading Gradients: Evaluating Evidence for Time-dependent Memory Reorganization in Experimental Animals

Directory of Open Access Journals (Sweden)

Katherine G. Akers

2009-01-01

Full Text Available In humans, hippocampal damage typically produces temporally graded retrograde amnesia, with relative sparing of remote memories compared to recent memories. This observation led to the idea that as memories age, they are reorganized in a time-dependent manner. Here, we evaluate evidence for time-dependent memory reorganization in animal models. We conclude that, although hippocampal lesions may not always produce temporal gradients under all conditions, studies using alternate experimental approaches consistently support the idea that memories reorganize over time—becoming less dependent on the hippocampus and more dependent on a cortical network. We further speculate on the processes that drive memory reorganization such as sleep, memory reactivation, synaptic plasticity, and neurogenesis.

Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

DEFF Research Database (Denmark)

Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

2018-01-01

activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...

Experimental models of autoimmune inflammatory ocular diseases

Directory of Open Access Journals (Sweden)

Fabio Gasparin

2012-04-01

Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

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.

Animal models in genomic research: Techniques, applications, and roles for nurses.

Science.gov (United States)

Osier, Nicole D; Pham, Lan; Savarese, Amanda; Sayles, Kendra; Alexander, Sheila A

2016-11-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

Following the genes: a framework for animal modeling of psychiatric disorders

Directory of Open Access Journals (Sweden)

Sawa Akira

2011-11-01

Full Text Available Abstract The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans.

Modelling the interactions between animal venom peptides and membrane proteins.

Science.gov (United States)

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

2017-12-01

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

Modelling group dynamic animal movement

DEFF Research Database (Denmark)

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

2014-01-01

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

Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

Science.gov (United States)

Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

2010-03-01

Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

Experimental task-based optimization of a four-camera variable-pinhole small-animal SPECT system

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Hesterman, Jacob Y.; Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.

2005-04-01

We have previously utilized lumpy object models and simulated imaging systems in conjunction with the ideal observer to compute figures of merit for hardware optimization. In this paper, we describe the development of methods and phantoms necessary to validate or experimentally carry out these optimizations. Our study was conducted on a four-camera small-animal SPECT system that employs interchangeable pinhole plates to operate under a variety of pinhole configurations and magnifications (representing optimizable system parameters). We developed a small-animal phantom capable of producing random backgrounds for each image sequence. The task chosen for the study was the detection of a 2mm diameter sphere within the phantom-generated random background. A total of 138 projection images were used, half of which included the signal. As our observer, we employed the channelized Hotelling observer (CHO) with Laguerre-Gauss channels. The signal-to-noise (SNR) of this observer was used to compare different system configurations. Results indicate agreement between experimental and simulated data with higher detectability rates found for multiple-camera, multiple-pinhole, and high-magnification systems, although it was found that mixtures of magnifications often outperform systems employing a single magnification. This work will serve as a basis for future studies pertaining to system hardware optimization.

Small Animal Models for Evaluating Filovirus Countermeasures.

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Banadyga, Logan; Wong, Gary; Qiu, Xiangguo

2018-05-11

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

Survey of basic medical researchers on the awareness of animal experimental designs and reporting standards in China.

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Bin Ma

Full Text Available To investigate the awareness and use of the Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE risk-of-bias tool, the Animal Research: Reporting of In Vivo Experiments (ARRIVE reporting guidelines, and Gold Standard Publication Checklist (GSPC in China in basic medical researchers of animal experimental studies.A national questionnaire-based survey targeting basic medical researchers was carried in China to investigate the basic information and awareness of SYRCLE's risk of bias tool, ARRIVE guidelines, GSPC, and animal experimental bias risk control factors. The EpiData3.1 software was used for data entry, and Microsoft Excel 2013 was used for statistical analysis in this study. The number of cases (n and percentage (% of classified information were statistically described, and the comparison between groups (i.e., current students vs. research staff was performed using chi-square test.A total of 298 questionnaires were distributed, and 272 responses were received, which included 266 valid questionnaires (from 118 current students and 148 research staff. Among the 266 survey participants, only 15.8% was aware of the SYRCLE's risk of bias tool, with significant difference between the two groups (P = 0.003, and the awareness rates of ARRIVE guidelines and GSPC were only 9.4% and 9.0%, respectively; 58.6% survey participants believed that the reports of animal experimental studies in Chinese literature were inadequate, with significant difference between the two groups (P = 0.004. In addition, only approximately 1/3 of the survey participants had read systematic reviews and meta-analysis reports of animal experimental studies; only 16/266 (6.0% had carried out/participated in and 11/266 (4.1% had published systematic reviews/meta-analysis of animal experimental studies.The awareness and use rates of SYRCLE's risk-of-bias tool, the ARRIVE guidelines, and the GSPC were low among Chinese basic medical researchers. Therefore

Compliance of the legal treatment of experimental animals in Serbian legislation with the legislation of the European Union

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Vidić-Trninić Jelena

2013-01-01

Full Text Available The author focuses on compliance of the legal treatment of experimental animals in Serbian law with the provisions of the European legislation. Analysing, on one hand, the treatment that experimental animals have under the law of European Union, and on the other hand, the treatment that they have in the law of Serbia, in accordance with the relevant acts and subordinate legislation acts, this article seeks to answer the question whether the degree of legal protection of experimental animals in domestic law is satisfactory, as well as whether and to what extent the relevant national legislation complies with the European standards. At the same time, the article attempts to point out the appropriate measures necessary to be taken in the future in order to achieve as high quality and comprehensive protection of experimental animals as possible in Serbian law.

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

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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.

Osteoarthritis: new insights in animal models.

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

2012-01-01

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

Animal models for microbicide safety and efficacy testing.

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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.

Steroid-associated osteonecrosis animal model in rats

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Li-Zhen Zheng

2018-04-01

lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction. Conclusion: The present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON. The translational potential of this article: The present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON. Keywords: Animal model, Corticosteroid, Osteonecrosis

Animal Models of Chemotherapy-induced Mucositis

DEFF Research Database (Denmark)

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

2018-01-01

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

Brain glucose metabolism in an animal model of depression.

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

2015-06-04

all experimental conditions, i.e., prenatal stress, acute stress, and glucose administration. Our data indicate that glycolysis is increased and the Krebs cycle is decreased in the brain of a prenatal stress animal model of depression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A new dietary model to study colorectal carcinogenesis: experimental design, food preparation, and experimental findings.

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Rozen, P; Liberman, V; Lubin, F; Angel, S; Owen, R; Trostler, N; Shkolnik, T; Kritchevsky, D

1996-01-01

Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

A Knockout Experiment: Disciplinary Divides and Experimental Skill in Animal Behaviour Genetics.

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Nelson, Nicole C

2015-07-01

In the early 1990s, a set of new techniques for manipulating mouse DNA allowed researchers to 'knock out' specific genes and observe the effects of removing them on a live mouse. In animal behaviour genetics, questions about how to deploy these techniques to study the molecular basis of behaviour became quite controversial, with a number of key methodological issues dissecting the interdisciplinary research field along disciplinary lines. This paper examines debates that took place during the 1990s between a predominately North American group of molecular biologists and animal behaviourists around how to design, conduct, and interpret behavioural knockout experiments. Drawing from and extending Harry Collins's work on how research communities negotiate what counts as a 'well-done experiment,' I argue that the positions practitioners took on questions of experimental skill reflected not only the experimental traditions they were trained in but also their differing ontological and epistemological commitments. Different assumptions about the nature of gene action, eg., were tied to different positions in the knockout mouse debates on how to implement experimental controls. I conclude by showing that examining representations of skill in the context of a community's knowledge commitments sheds light on some of the contradictory ways in which contemporary animal behaviour geneticists talk about their own laboratory work as a highly skilled endeavour that also could be mechanised, as easy to perform and yet difficult to perform well.

Experimentação animal: ética e legislação brasileira Animal experimentation: ethics and the Brazilian legislation

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Angélica Heringer de Rezende

2008-04-01

Full Text Available Este artigo trata da experimentação animal sob os pontos de vista da ética e da política, fazendo uma abordagem histórica do tema no cenário legislativo brasileiro. Os animais de laboratório desempenharam um papel decisivo para o desenvolvimento da ciência e continuam tendo um papel essencial na pesquisa biomédica, no entanto, sua utilização sempre despertou manifestação de diferentes naturezas. Apesar de as primeiras incursões na pesquisa experimental terem sido iniciadas há, pelo menos, quatro séculos, é incipiente o estabelecimento de normas que regulamentem a utilização de animais na América Latina. No Brasil, embora não haja uma lei específica em relação a essa utilização, algumas iniciativas já foram tomadas. As discussões sobre este tema continuam ocorrendo, contudo, a demora para definir uma lei que regulamente o uso de animais em pesquisa tem dificultado a padronização de procedimentos necessários à sistematização dos conhecimentos desenvolvidos no País.This article covers animal experimentation under the viewpoint of ethics and politics, and does a historical review of the theme in the Brazilian legislative scenario. Laboratory animals play a decisive role in the development of science and continue to have an essential role in biomedical research. However, their use always provoked manifestations of different natures. Even though the first incursions in experimental research began at least four centuries ago, the establishment of norms that regulate the use of animals in Latin America is incipient. In Brazil, although a specific law regarding this use does not exist, some initiatives have already been taken. The discussions on this theme continue to happen, however the delay to define a law that regulates the use of animals in research has hindered the standardization of procedures that are necessary to the systematization of the knowledge produced in the country.

Modelos animais de aneurisma de aorta Animal models of aortic aneurysm

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Rodrigo Argenta

2009-06-01

Full Text Available Os modelos experimentais em animais vêm sendo utilizados em cirurgia vascular há décadas. O desenvolvimento de novas técnicas para tratamento endovascular dos aneurismas requer a criação de bons modelos experimentais para testar esses dispositivos e estudar seu impacto sobre a progressão da doença. Este artigo tem por objetivo revisar os modelos de aneurisma arterial descritos atualmente. Entre os diversos modelos descritos, nenhum reúne todas as características de um modelo ideal de aneurisma. Os modelos em animais de grande porte são adequados para treino, estudo de alterações em parâmetros fisiológicos durante e após a liberação dos dispositivos e integração do mesmo à parede do vaso. Algumas desvantagens significantes incluem dificuldade do manejo, alto custo, difícil manutenção e regulamentações legais, dificultando a disponibilidade de diversas espécies animais. Modelos em animais menores, como os coelhos e camundongos, embora sejam menos caros e de fácil obtenção, não são adequados para estudos de técnicas endovasculares pelas pequenas dimensões de seus vasos. Nenhum modelo descrito até o momento consegue reproduzir todas as características dos aneurismas observados em humanos. Modelos disponíveis são descritos nesta revisão, e suas vantagens e desvantagens são discutidas.Experimental animal models have been used in vascular surgery for decades. The development of new interventional techniques in the endovascular treatment of aneurysms requires the creation of good experimental models to test these devices and study their impact on disease progression. The aim of this article was to review arterial aneurysm models currently available. Several distinct models have been described but none of them satisfies all the requirements of an ideal aneurysm model. Large animal models are appropriate for training, study of alterations in physiological parameters during and after device delivery, and integration

Impact of animal waste application on runoff water quality in field experimental plots.

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Hill, Dagne D; Owens, William E; Tchoounwou, Paul B

2005-08-01

Animal waste from dairy and poultry operations is an economical and commonly used fertilizer in the state of Louisiana. The application of animal waste to pasture lands not only is a source of fertilizer, but also allows for a convenient method of waste disposal. The disposal of animal wastes on land is a potential nonpoint source of water degradation. Water degradation and human health is a major concern when considering the disposal of large quantities of animal waste. The objective of this research was to determine the effect of animal waste application on biological (fecal coliform, Enterobacter spp. and Escherichia coli) and physical/chemical (temperature, pH, nitrate nitrogen, ammonia nitrogen, phosphate, copper, zinc, and sulfate) characteristics of runoff water in experimental plots. The effects of the application of animal waste have been evaluated by utilizing experimental plots and simulated rainfall events. Samples of runoff water were collected and analyzed for fecal coliforms. Fecal coliforms isolated from these samples were identified to the species level. Chemical analysis was performed following standard test protocols. An analysis of temperature, ammonia nitrogen, nitrate nitrogen, iron, copper, phosphate, potassium, sulfate, zinc and bacterial levels was performed following standard test protocols as presented in Standard Methods for the Examination of Water and Wastewater [1]. In the experimental plots, less time was required in the tilled broiler litter plots for the measured chemicals to decrease below the initial pre-treatment levels. A decrease of over 50% was noted between the first and second rainfall events for sulfate levels. This decrease was seen after only four simulated rainfall events in tilled broiler litter plots whereas broiler litter plots required eight simulated rainfall events to show this same type of reduction. A reverse trend was seen in the broiler litter plots and the tilled broiler plots for potassium. Bacteria numbers

Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

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Capelozzi, Marco A; Leick-Maldonado, Edna A; Parra, Edwin R; Martins, Mílton A; Tibério, Iolanda F L C; Capelozzi, Vera L

2007-05-14

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

Animal models for dengue vaccine development and testing.

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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.

The influence of feeding GMO-peas on growth of animal models

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Petr Mares

2014-02-01

Full Text Available Introduction of genetically modified (GM food or feed into the commercial sale represents a very complicated process. One of the most important steps in approval process is the evaluation of all risks on the health status of people and animal models. Within our project the genetically modified peas was breeded that showed significant resistance against Pea seed-borne mosaic virus and Pea enation mosaic virus. Preclinical studies have been conducted to found out the effect of GMO peas on animals - rats of outbreeding line Wistar. In a total, 24 male, specific pathogen free Wistar rats were used in the experiment. At the beginning of the experiment, the animals were 28 days old. The three experimental groups with 8 individuals were created. The first group of rats was fed with GMO peas, the second group of rats consumed mix of pea cultivar Raman and the third group was control without pea addition (wheat and soya were used instead of pea. In the present study we focused our attention on health, growth and utility features of rats fed with GM pea. All characteristic were observed during the experiment lasting 35 days. Consumed feed was weighted daily and the weight of the animals was measured every seven days. The average values were compared within the groups. The aim of the experiment was to verify if resistant lines of pea influence the weight growth of animal models. The results of our experiment showed that even a high concentration (30% of GM pea did not influence growth rate of rats to compare with both rats fed with pea of Raman cultivar and control group. We did not observe any health problems of animal models during the experiment.

Animal models of pancreatic cancer for drug research.

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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.

Latest animal models for anti-HIV drug discovery.

Science.gov (United States)

Sliva, Katja

2015-02-01

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

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

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

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Mulak, Agata; Taché, Yvette

2011-01-01

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

Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

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Iveta Bernatova

2014-01-01

Full Text Available Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP. The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (prehypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

Testing Experimental Compounds against Leishmaniansis in Laboratory Animal Model Systems

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1984-09-01

consulted in five human and two canine cases of suspected leishmaniasis. Two of the 5 human cases were isoenzyme typed as L. b. braziliensis ( Peru ...animal. The latter may be of use in controlling some of the complications of diabetes . %’Wr WF ’ 56 PU BLICAT I ONS_ Griffith, O.W., "Mechanism of

The necessity of animal models in pain research.

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

2010-10-01

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

Stem cell therapy for joint problems using the horse as a clinically relevant animal model

DEFF Research Database (Denmark)

Koch, Thomas Gadegaard; Betts, Dean H.

2007-01-01

of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

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.

Pathogenesis of Mycobacterium bovis Infection: the Badger Model As a Paradigm for Understanding Tuberculosis in Animals

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Eamonn Gormley

2018-01-01

Full Text Available Tuberculosis in animals is caused principally by infection with Mycobacterium bovis and the potential for transmission of infection to humans is often the fundamental driver for surveillance of disease in livestock and wild animals. However, with such a vast array of species susceptible to infection, it is often extremely difficult to gain a detailed understanding of the pathogenesis of infection––a key component of the epidemiology in all affected species. This is important because the development of disease control strategies in animals is determined chiefly by an understanding of the epidemiology of the disease. The most revealing data from which to formulate theories on pathogenesis are that observed in susceptible hosts infected by natural transmission. These data are gathered from detailed studies of the distribution of gross and histological lesions, and the presence and distribution of infection as determined by highly sensitive bacteriology procedures. The information can also be used to establish the baseline for evaluating experimental model systems. The European badger (Meles meles is one of a very small number of wild animal hosts where detailed knowledge of the pathogenesis of M. bovis infection has been generated from observations in natural-infected animals. By drawing parallels from other animal species, an experimental badger infection model has also been established where infection of the lower respiratory tract mimics infection and the disease observed in natural-infected badgers. This has facilitated the development of diagnostic tests and testing of vaccines that have the potential to control the disease in badgers. In this review, we highlight the fundamental principles of how detailed knowledge of pathogenesis can be used to evaluate specific intervention strategies, and how the badger model may be a paradigm for understanding pathogenesis of tuberculosis in any affected wild animal species.

Effects of experimental radiotherapy and hyperthermia on tumors and normal tissues in small animals

International Nuclear Information System (INIS)

Wondergem, J.

1985-01-01

Experiments on responses of tumors, implanted subcutaneously in the leg, to irradiation alone or combined with heat are reported. The influence of factors modifying the fraction of hypoxic cells (e.g. anesthesia of the animal and tumor volume) is also discussed. The radiosensitivity of developing lung tumors was examined for spontaneous as well as for artificial lung metastases. Both experimental tumor models were compared with regard to their value in experimental radiotherapy. Data obtained on the response of artificial metastases and lung tissue to combined treatment with irradiation and several drugs are presented. Data on damage of the mouse foot, as a result of heat and/or irradiation treatments are presented. In particular the influence of thermotolerance on thermal enhancement of the radiation induced skin reaction was studied. Tolerance of the skin of previously irradiated mice to retreatment with irradiation, to hyperthermia alone and combined with X-rays was assessed. (Auth.)

Animation of 3D Model of Human Head

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V. Michalcin

2007-04-01

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

Modeling collective animal behavior with a cognitive perspective: a methodological framework.

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Sebastian Weitz

Full Text Available The last decades have seen an increasing interest in modeling collective animal behavior. Some studies try to reproduce as accurately as possible the collective dynamics and patterns observed in several animal groups with biologically plausible, individual behavioral rules. The objective is then essentially to demonstrate that the observed collective features may be the result of self-organizing processes involving quite simple individual behaviors. Other studies concentrate on the objective of establishing or enriching links between collective behavior researches and cognitive or physiological ones, which then requires that each individual rule be carefully validated. Here we discuss the methodological consequences of this additional requirement. Using the example of corpse clustering in ants, we first illustrate that it may be impossible to discriminate among alternative individual rules by considering only observational data collected at the group level. Six individual behavioral models are described: They are clearly distinct in terms of individual behaviors, they all reproduce satisfactorily the collective dynamics and distribution patterns observed in experiments, and we show theoretically that it is strictly impossible to discriminate two of these models even in the limit of an infinite amount of data whatever the accuracy level. A set of methodological steps are then listed and discussed as practical ways to partially overcome this problem. They involve complementary experimental protocols specifically designed to address the behavioral rules successively, conserving group-level data for the overall model validation. In this context, we highlight the importance of maintaining a sharp distinction between model enunciation, with explicit references to validated biological concepts, and formal translation of these concepts in terms of quantitative state variables and fittable functional dependences. Illustrative examples are provided of the

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

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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…

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

Lung cancer risk models from experimental animals

International Nuclear Information System (INIS)

Gilbert, E.S.

1988-03-01

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

Review: To be or not to be an identifiable model. Is this a relevant question in animal science modelling?

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Muñoz-Tamayo, R; Puillet, L; Daniel, J B; Sauvant, D; Martin, O; Taghipoor, M; Blavy, P

2018-04-01

What is a good (useful) mathematical model in animal science? For models constructed for prediction purposes, the question of model adequacy (usefulness) has been traditionally tackled by statistical analysis applied to observed experimental data relative to model-predicted variables. However, little attention has been paid to analytic tools that exploit the mathematical properties of the model equations. For example, in the context of model calibration, before attempting a numerical estimation of the model parameters, we might want to know if we have any chance of success in estimating a unique best value of the model parameters from available measurements. This question of uniqueness is referred to as structural identifiability; a mathematical property that is defined on the sole basis of the model structure within a hypothetical ideal experiment determined by a setting of model inputs (stimuli) and observable variables (measurements). Structural identifiability analysis applied to dynamic models described by ordinary differential equations (ODEs) is a common practice in control engineering and system identification. This analysis demands mathematical technicalities that are beyond the academic background of animal science, which might explain the lack of pervasiveness of identifiability analysis in animal science modelling. To fill this gap, in this paper we address the analysis of structural identifiability from a practitioner perspective by capitalizing on the use of dedicated software tools. Our objectives are (i) to provide a comprehensive explanation of the structural identifiability notion for the community of animal science modelling, (ii) to assess the relevance of identifiability analysis in animal science modelling and (iii) to motivate the community to use identifiability analysis in the modelling practice (when the identifiability question is relevant). We focus our study on ODE models. By using illustrative examples that include published

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....

Impact of Animal Waste Application on Runoff Water Quality in Field Experimental Plots

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Paul B. Tchounwou

2005-08-01

Full Text Available Animal waste from dairy and poultry operations is an economical and commonly used fertilizer in the state of Louisiana. The application of animal waste to pasture lands not only is a source of fertilizer, but also allows for a convenient method of waste disposal. The disposal of animal wastes on land is a potential nonpoint source of water degradation. Water degradation and human health is a major concern when considering the disposal of large quantities of animal waste. The objective of this research was to determine the effect of animal waste application on biological (fecal coliform, Enterobacter spp. and Escherichia coli and physical/chemical (temperature, pH, nitrate nitrogen, ammonia nitrogen, phosphate, copper, zinc, and sulfate characteristics of runoff water in experimental plots. The effects of the application of animal waste have been evaluated by utilizing experimental plots and simulated rainfall events. Samples of runoff water were collected and analyzed for fecal coliforms. Fecal coliforms isolated from these samples were identified to the species level. Chemical analysis was performed following standard test protocols. An analysis of temperature, ammonia nitrogen, nitrate nitrogen, iron, copper, phosphate, potassium, sulfate, zinc and bacterial levels was performed following standard test protocols as presented in Standard Methods for the Examination of Water and Wastewater [1]. In the experimental plots, less time was required in the tilled broiler litter plots for the measured chemicals to decrease below the initial pre-treatment levels. A decrease of over 50% was noted between the first and second rainfall events for sulfate levels. This decrease was seen after only four simulated rainfall events in tilled broiler litter plots whereas broiler litter plots required eight simulated rainfall events to show this same type of reduction. A reverse trend was seen in the broiler litter plots and the tilled broiler plots for potassium

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.

Animal experimentation in Spacelab - Present and future U.S. plans

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Berry, W. E.; Dant, C. C.

1983-01-01

Current development of life-sciences hardware and experiments for the fourth Spacelab mission in the Life Sciences Flight Experiments Program at NASA Ames is reviewed. The research-animal holding facility, the general-purpose work station, and the life sciences laboratory equipment are characterized, and the 14 Ames projects accepted for the mission are listed and discussed. Several hardware systems and experimental procedures will be verified on the Spacelab-3 mission scheduled for late 1984.

Human-animal relationships: from daily life to animal-assisted therapies

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Marine Grandgeorge

2011-12-01

Full Text Available Humans have a long history of relationship with domestic animals and nowadays pets often act as "social substitutes" through bonding. There is some evidence that pet presence at home may induce well being in people and the development of social skills in children. Animal assisted therapies aim at developing these skills in patients on the basis of human animal interactions. Experimental data obtained on animal models suggest that this is indeed a promising line. There is however a lack of clear scientific data that would help defines what the most appropriate procedures or species may be. Improvements are observed, but again sound scientific data are mostly missing. Attention must be given to the welfare of the animals being used.

Elements of episodic-like memory in animal models.

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Crystal, Jonathon D

2009-03-01

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

Statistics of Scientific Procedures on Living Animals 2014: A new format, and hopefully a new era of diminishing animal experimentation?

Science.gov (United States)

Hudson-Shore, Michelle

2016-03-01

The Annual Statistics of Scientific Procedures on Living Animals Great Britain 2014 reports a welcome decline in animal experimentation in the UK. However, caution has to be exercised when interpreting these most recent figures, due to the significant changes made to satisfy the requirements of Directive 2010/63/EU as to what information is reported and how it is reported. Comparisons to the figures and trends reported in previous years is difficult, so this paper focuses on the specifics of the current report, providing information on overall animal use and highlighting specific issues associated with genetically-altered animals, fish and primates. There is a detailed discussion of the extent of the changes, commenting on the benefits and disadvantages of the new format, in areas such as severity of procedures, legislation and techniques of special interest. It also considers the consequences of the changes on the effective monitoring of laboratory animal use, the openness and transparency regarding the impacts of animal use, and the implementation of Three Rs initiatives. In addition, suggestions for further improvements to the new format are made to the Home Office. 2016 FRAME.

Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia.

Science.gov (United States)

Burrows, Emma L; Hannan, Anthony J

2016-04-01

Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental In Vivo Models of Candidiasis

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Esther Segal

2018-02-01

Full Text Available Candidiasis is a multifaceted fungal disease including mucosal-cutaneous, visceral, and disseminated infections caused by yeast species of the genus Candida. Candida infections are among the most common human mycoses. Candida species are the third to fourth most common isolates from bloodstream infections in neutropenic or immunocompromised hospitalized patients. The mucosal-cutaneous forms—particularly vaginal infections—have a high prevalence. Vaginitis caused by Candida species is the second most common vaginal infection. Hence, candidiasis is a major subject for research, including experimental in vivo models to study pathogenesis, prevention, or therapy of the disease. The following review article will focus on various experimental in vivo models in different laboratory animals, such as mammals (mice, rats, rabbits, the fruit fly–Drosophila melanogaster, the larvae of the moth Galleria mellonella, or the free-living nematode Caenorhabditis elegans. The review will describe the induction of the different clinical forms of candidiasis in the various models and the validity of such models in mimicking the human clinical situations. The use of such models for the assessment of antifungal drugs, evaluation of potential vaccines to protect before candidiasis, exploration of Candida virulence factors, and comparison of pathogenicity of different Candida species will be included in the review. All of the above will be reported as based on published studies of numerous investigators as well as on the research of the author and his group.

DOES AEROBIC EXERCISE TRAINING PROMOTE CHANGES IN STRUCTURAL AND BIOMECHANICAL PROPERTIES OF THE TENDONS IN EXPERIMENTAL ANIMALS? A SYSTEMATIC REVIEW

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Márcio A. Bezerra

2012-11-01

Full Text Available To develop a systematic review to evaluate, through the best scientific evidence available, the effectiveness of aerobic exercise in improving the biomechanical characteristics of tendons in experimental animals. Two independent assessors conducted a systematic search in the databases Medline/PUBMED and Lilacs/BIREME, using the following descriptors of Mesh in animal models. The ultimate load of traction and the elastic modulus tendon were used as primary outcomes and transverse section area, ultimate stress and tendon strain as secondary outcomes. The assessment of risk of bias in the studies was carried out using the following methodological components: light/dark cycle, temperature, nutrition, housing, research undertaken in conjunction with an ethics committee, randomization, adaptation of the animals to the training and preparation for the mechanical test. Eight studies, comprising 384 animals, were selected; it was not possible to combine them into one meta-analysis due to the heterogeneity of the samples. There was a trend to increasing ultimate load without changes in the other outcomes studied. Only one study met more than 80% of the quality criteria. Physical training performed in a structured way with imposition of overloads seems to be able to promote changes in tendon structure of experimental models by increasing the ultimate load supported. However, the results of the influence of exercise on the elastic modulus parameters, strain, transverse section area and ultimate stress, remain controversial and inconclusive. Such a conclusion must be evaluated with reservation as there was low methodological control in the studies included in this review.

Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

International Nuclear Information System (INIS)

Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

2017-01-01

Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

Animal models for Gaucher disease research

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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.

Animal models for Gaucher disease research.

Science.gov (United States)

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

2011-11-01

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

Final model of multicriterionevaluation of animal welfare

DEFF Research Database (Denmark)

Bonde, Marianne; Botreau, R; Bracke, MBM

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

Evaluation of cross-protection by immunization with an experimental trivalent companion animal periodontitis vaccine in the mouse periodontitis model.

Science.gov (United States)

Hardham, John; Sfintescu, Cornelia; Evans, Richard T

2008-03-01

Companion animal periodontal disease is one of the most prevalent diseases seen by veterinarians. The goal of this study was to evaluate the vaccine performance of a trivalent canine periodontitis vaccine in the mouse oral challenge model of periodontitis. Mice vaccinated subcutaneously with an inactivated, whole-cell vaccine preparation of Porphyromonas denticanis, Porphyromonas gulae, and Porphyromonas salivosa displayed significantly reduced alveolar bone loss in response to heterologous and cross-species challenges as compared to sham vaccinated animals. Based on the results of these studies, a periodontitis vaccine may be a useful tool in preventing the initiation and progression of periodontitis caused by the most commonly isolated pigmenting anaerobic bacteria in animals.

Preclinical experimental models of drug metabolism and disposition in drug discovery and development

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Donglu Zhang

2012-12-01

Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.

Alternatives to animal experimentation in basic research.

Science.gov (United States)

Gruber, Franz P; Hartung, Thomas

2004-01-01

methods, even if published in the scientific literature, are little standardised and reproducible. The suggestion is put forward that publicly accessible databases should make available more detailed descriptions of methodologies. Due to limitations in space, many scientific journals cannot publish detailed methodological descriptions. However, nowadays a supplementary central deposit of methods could easily be linked to the respective article. In numerous cases though, there is simply a lack of will to change procedures to methods without animal tests or to pose questions differently in order to avoid the use of animals or to reduce their number or, at least, to reduce stress. In other cases, researchers are simply not aware of the limitations of the animal experiment as such. A thorough review of the validity of critical animal experiments should be carried out and made available publicly. For example, many animal experiments are dramatically "under-powered", i.e. carried out with groups that are too small to allow conclusions to be drawn from the outcome. This stands in marked contrast to in vitro experiments where replicate experiments usually represent no major problem. Since in vitro models are generally more prone to artefacts due to the numerous variables, e.g. of cell culture, the key requirement for their application is their validation and quality control. Guided by the experience from validation studies for alternative methods in toxicology, concepts of a Good Cell Culture Practice (GCCP) are currently being developed which aim to define minimum quality standards for in vitro techniques. This initiative aiming to increase quality must be complemented by a concept to systematically assess the relevance of the tests in order to finally achieve an evidence-based biomedical research. A change in this direction is only possible if those public funds, which were previously assigned predominantly to alternatives to the animal tests required by law, are now channelled

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

Drug induced acute kidney injury: an experimental animal study

International Nuclear Information System (INIS)

Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

2017-01-01

Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

Studies on the effects of ionizing radiation on the normal and diseased liver in experimental animals

International Nuclear Information System (INIS)

Mahmoud, S.A.

1981-01-01

The experiments carried out in the present study primarily concerned with the effects of ionizing radiations on the normal and diseased liver in experimental animals (mice). Different radiation intensities and different exposure schemes were used to irradiate both healthy and schistosoma mansoni infected animals. A group of uninfected and unirradiated animals were used as controls. Follow up studies were performed every 6 weeks for 30 weeks. These included histopathological studies of the liver damage at every observation periods for all animal groups

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

Experimental Object-Oriented Modelling

DEFF Research Database (Denmark)

Hansen, Klaus Marius

through, e.g., technical prototyping and active user involvement. We introduce and examine “experimental object-oriented modelling” as the intersection of these practices. The contributions of this thesis are expected to be within three perspectives on models and modelling in experimental system...... development: Grounding We develop an empirically based conceptualization of modelling and use of models in system development projects characterized by a high degree of uncertainty in requirements and point to implications for tools and techniques for modelling in such a setting. Techniques We introduce......This thesis examines object-oriented modelling in experimental system development. Object-oriented modelling aims at representing concepts and phenomena of a problem domain in terms of classes and objects. Experimental system development seeks active experimentation in a system development project...

Plasma rico em plaquetas de coelhos: introdução a um modelo animal experimental Platelet-rich plasma in rabbits: introduction of one experimental animal model

Directory of Open Access Journals (Sweden)

Marco Antonio de Oliveira-Filho

2008-12-01

Full Text Available RACIONAL: Muitas dúvidas ainda permanecem no que se refere às ações dos fatores de crescimento e do plasma rico em plaquetas sobre o mecanismo de reparação tissular. Há necessidade de serem esclarecidos pontos controversos ainda existentes. OBJETIVO: Obter o plasma rico em plaquetas em coelhos através de um método simplificado e ao mesmo tempo adequado, introduzindo um modelo experimental que possa ser utilizado em estudos posteriores. MÉTODOS: Foram utilizados 25 coelhas da raça Nova Zelândia e sem doenças prévias. Quinze mL de sangue de cada animal foi coletado, sendo 10 mL submetidos à dupla centrifugação. Para comprovar a efetividade do método proposto realizou-se contagem mecânica do sangue, bem como do produto final. RESULTADO: Obteve-se uma concentração média de plaquetas no plasma rico em plaquetas 687% maior que a contagem inicial observada no sangue venoso periférico. Para as variáveis: contagem inicial de plaquetas, contagem de plaquetas no plasma rico em plaquetas e enriquecimento, foram obtidos os limites de 95% de confiança para suas médias, sendo que, no que se refere ao percentual de enriquecimento, existe 95% de chance de que o intervalo de (530-844 contenha a média real de enriquecimento de plaquetas. CONCLUSÃO: O método simplificado utilizado permite a obtenção de plasma rico em plaquetas adequado permitindo seu uso em estudos dos fatores de crescimento nos mecanismos de reparação tecidual.BACKGROUND: Multiple uncertainties still exist about the action of the growth factors and the platelet-rich plasma on the mechanism of repair. AIM: To obtain the platelet-rich plasma in rabbits through a simplified and suitable method, creating an experimental model. METHODS: Twenty-five female New Zealand rabbits without previous diseases were used. Fifteen mL of blood of each rabbit was collected and 10 mL of the collected blood were twice centrifugated. To check the effectiveness of the proposed method

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

Animal experimentations: Part I: General considerations

Directory of Open Access Journals (Sweden)

T K Pal

2015-01-01

Full Text Available All materials, in the form of drugs or devices, which are intended for human use are required to be tested first in suitable animals. Many biological understandings are established on various modes of cruelties on animals. This observational notes guide us to accept or modify or even reject materials for ultimate human use. The science of experiments on animals gives us the remedial solutions to many of our human sufferings. This unique and important discipline is in need of proper understanding for selection of suitable number of animals and its proper care in captivity, and further refinements of code of conducts and ethical issues.

Animal models of drug addiction.

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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.

Osteoarthritis: New Insights in Animal Models

OpenAIRE

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

2012-01-01

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

Experimental Models Used in Fat Grafting Research for Volume Augmentation in Soft Tissue Reconstruction

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Jorge Lujan-Hernandez

2017-09-01

Full Text Available As the popularity of fat grafting research increases, animal models are being used as the source of pre-clinical experimental information for discovery and to enhance techniques. To date, animal models used in this research have not been compared to provide a standardized model. We analyzed publications from 1968–2015 to compare published accounts of animal models in fat grafting research. Data collected included: species used, graft characteristics (donor tissue, recipient area, amount injected, injection technique, time of sacrifice and quantification methods. Mice were most commonly used (56% of studies, with the “athymic nude” strain utilized most frequently (44%. Autologous fat was the most common source of grafted tissue (52%. Subcutaneous dorsum was the most common recipient site (51%. On average, 0.80±0.60 mL of fat was grafted. A single bolus technique was used in 57% of studies. Fat volume assessment was typically completed at the end of the study, occurring at less than 1 week to one year. Graft volume was quantified by weight (63%, usually in conjunction with another analysis. The results demonstrate the current heterogeneity of animal models in this research. We propose that the research community reach a consensus to allow better comparison of techniques and results. One example is the model used in our laboratory and others; this model is described in detail. Eventually, larger animal models may better translate to the human condition but, given increased financial costs and animal facility capability, should be explored when data obtained from small animal studies is exhausted or inconclusive.

The Magnus-Rademaker Scientific Film Collection: Ethical Issues on Animal Experimentation (1908-1940).

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Koehler, Peter J; Lameris, Bregt

2016-01-01

The Magnus-Rademaker scientific film collection (1908-1940) deals with the physiology of body posture by the equilibrium of reflex musculature contractions for which experimental studies were carried out with animals (e.g., labyrinthectomies, cerebellectomies, and brain stem sections) as well as observations done on patients. The films were made for demonstrations at congresses as well as educational objectives and film stills were published in their books. The purpose of the present study is to position these films and their makers within the contemporary discourse on ethical issues and animal rights in the Netherlands and the earlier international debates. Following an introduction on animal rights and antivivisection movements, we describe what Magnus and Rademaker thought about these issues. Their publications did not provide much information in this respect, probably reflecting their adherence to implicit ethical codes that did not need explicit mentioning in publications. Newspaper articles, however, revealed interesting information. Unnecessary suffering of an animal never found mercy in Magnus' opinion. The use of cinematography was expanded to the reduction of animal experimentation in student education, at least in the case of Rademaker, who in the 1930s was involved in a governmental committee for the regulation of vivisection and cooperated with the antivivisection movement. This resulted not only in a propaganda film for the movement but also in films that demonstrate physiological experiments for students with the purpose to avert repetition and to improve the teaching of experiments. We were able to identify the pertinent films in the Magnus-Rademaker film collection. The production of vivisection films with this purpose appears to have been common, as is shown in news messages in European medical journals of the period.

Huntington disease: Experimental models and therapeutic perspectives

International Nuclear Information System (INIS)

Serrano Sanchez, Teresa; Blanco Lezcano, Lisette; Garcia Minet, Rocio; Alberti Amador, Esteban; Diaz Armesto, Ivan and others

2011-01-01

Huntington's disease (HD) is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment to the disease which having lapsed 15 or 20 years advances inexorably, in a slow form, toward the total inability or death. This paper reviews the clinical and morphological characteristics of Huntington's disease as well as the experimental models more commonly used to study this disease, having as source the articles indexed in Medline data base, published in the last 20 years. Advantages and disadvantages of all experimental models to reproduce the disease as well as the perspectives to therapeutic assay have been also considered. the consent of outline reported about the toxic models, those induced by neurotoxins such as quinolinic acid, appears to be the most appropriate to reproduce the neuropathologic characteristic of the disease, an genetic models contributing with more evidence to the knowledge of the disease etiology. Numerous treatments ameliorate clinical manifestations, but none of them has been able to stop or diminish the affectations derived from neuronal loss. At present time it is possible to reproduce, at least partially, the characteristics of the disease in experimentation animals that allow therapy evaluation in HD. from the treatment view point, the more promissory seems to be transplantation of no neuronal cells, taking into account ethical issues and factibility. On the other hand the new technology of interference RNA emerges as a potential therapeutic tool for treatment in HD, and to respond basic questions on the development of the disease.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

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Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

2010-06-01

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

Polycystic ovarian disease: animal models.

Science.gov (United States)

Mahajan, D K

1988-12-01

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

Controlled reperfusion decreased reperfusion induced oxidative stress and evoked inflammatory response in experimental aortic-clamping animal model.

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Jancsó, G; Arató, E; Hardi, P; Nagy, T; Pintér, Ö; Fazekas, G; Gasz, B; Takacs, I; Menyhei, G; Kollar, L; Sínay, L

2016-09-12

Revascularization after long term aortic ischaemia in vascular surgery induces reperfusion injury accompanied with oxidative stress and inflammatory responses. The hypothesis of this study was that the aortic occlusion followed by controlled reperfusion (CR) can reduce the ischaemia-reperfusion injury, the systemic and local inflammatory response induced by oxidative stress.Animal model was used. animals underwent a 4-hour infrarenal aortic occlusion followed by continuous reperfusion. Treated group: animals were treated with CR: after a 4-hour infrarenal aortic occlusion we made CR for 30 minutes with the crystalloid reperfusion solution (blood: crystalloid solution ratio 1:1) on pressure 60 Hgmm. Blood samples were collected different times. The developing oxidative stress was detected by the plasma levels of malondialdehyde, reduced glutathion, thiol groups and superoxide dismutase. The inflammatory response was measured by phorbol myristate acetate-induced leukocyte reactive oxygen species production and detection of change in myeloperoxidase levels. The animals were anaesthetized one week after terminating ligation and biopsy was taken from quadriceps muscle and large parenchymal organs.CR significantly reduced the postischaemic oxydative stress and inflammatory responses in early reperfusion period. Pathophysiological results: The rate of affected muscle fibers by degeneration was significantly higher in the untreated animal group. The infiltration of leukocytes in muscle and parenchymal tissues was significantly lower in the treatedgroup.CR can improve outcome after acute lower-limb ischaemia. The results confirm that CR might be also a potential therapeutic approach in vascular surgery against reperfusion injury in acute limb ischaemia. Supported by OTKA K108596.

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

Science.gov (United States)

Herati, Ramin Sedaghat; Wherry, E John

2018-04-02

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

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.

Bone augmentation for cancellous bone- development of a new animal model

Science.gov (United States)

2013-01-01

. The harvesting and evaluative methods assured a standardized analysis of all samples. Conclusions This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty. PMID:23819858

Classic and New Animal Models of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Javier Blesa

2012-01-01

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

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.

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

Directory of Open Access Journals (Sweden)

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.

[A NEW APPROACH FOR FOOD PREFERENCE TESTING IN ANIMAL EXPERIMENTATION].

Science.gov (United States)

Albertin, S V

2015-10-01

An article describes the original method allowing to study a mechanism of food preference related to the sensory properties of foods in animals. The method gives a good possibility to select the role of visual and orosensory signaling in food preference as well as to model the processes of physiological and pathological food and drug dependence in animal experiments. The role of discrete food presentation in the formation of the current motivations and food preferences was discussed.

Animal models in plastic and reconstructive surgery simulation-a review.

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Loh, Charles Yuen Yung; Wang, Aline Yen Ling; Tiong, Vincent Tze Yang; Athanassopoulos, Thanassi; Loh, Meiling; Lim, Philip; Kao, Huang-Kai

2018-01-01

The use of live and cadaveric animal models in surgical training is well established as a means of teaching and improving surgical skill in a controlled setting. We aim to review, evaluate, and summarize the models published in the literature that are applicable to Plastic Surgery training. A PubMed search for keywords relating to animal models in Plastic Surgery and the associated procedures was conducted. Animal models that had cross over between specialties such as microsurgery with Neurosurgery and pinnaplasty with ear, nose, and throat surgery were included as they were deemed to be relevant to our training curriculum. A level of evidence and recommendation assessment was then given to each surgical model. Our review found animal models applicable to plastic surgery training in four major categories namely-microsurgery training, flap raising, facial surgery, and hand surgery. Twenty-four separate articles described various methods of practicing microsurgical techniques on different types of animals. Fourteen different articles each described various methods of conducting flap-based procedures which consisted of either local or perforator flap dissection. Eight articles described different models for practicing hand surgery techniques. Finally, eight articles described animal models that were used for head and neck procedures. A comprehensive summary of animal models related to plastic surgery training has been compiled. Cadaveric animal models provide a readily available introduction to many procedures and ought to be used instead of live models when feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Synthetic torpor: A method for safely and practically transporting experimental animals aboard spaceflight missions to deep space

Science.gov (United States)

Griko, Yuri; Regan, Matthew D.

2018-02-01

Animal research aboard the Space Shuttle and International Space Station has provided vital information on the physiological, cellular, and molecular effects of spaceflight. The relevance of this information to human spaceflight is enhanced when it is coupled with information gleaned from human-based research. As NASA and other space agencies initiate plans for human exploration missions beyond low Earth orbit (LEO), incorporating animal research into these missions is vitally important to understanding the biological impacts of deep space. However, new technologies will be required to integrate experimental animals into spacecraft design and transport them beyond LEO in a safe and practical way. In this communication, we propose the use of metabolic control technologies to reversibly depress the metabolic rates of experimental animals while in transit aboard the spacecraft. Compared to holding experimental animals in active metabolic states, the advantages of artificially inducing regulated, depressed metabolic states (called synthetic torpor) include significantly reduced mass, volume, and power requirements within the spacecraft owing to reduced life support requirements, and mitigated radiation- and microgravity-induced negative health effects on the animals owing to intrinsic physiological properties of torpor. In addition to directly benefitting animal research, synthetic torpor-inducing systems will also serve as test beds for systems that may eventually hold human crewmembers in similar metabolic states on long-duration missions. The technologies for inducing synthetic torpor, which we discuss, are at relatively early stages of development, but there is ample evidence to show that this is a viable idea and one with very real benefits to spaceflight programs. The increasingly ambitious goals of world's many spaceflight programs will be most quickly and safely achieved with the help of animal research systems transported beyond LEO; synthetic torpor may

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

Science.gov (United States)

Bosmans, Joanna W A M; Moossdorff, Martine; Al-Taher, Mahdi; van Beek, Lotte; Derikx, Joep P M; Bouvy, Nicole D

2016-05-01

This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

Of mice and men: how animal models advance our understanding of T-cell function in RA.

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Kobezda, Tamás; Ghassemi-Nejad, Sheida; Mikecz, Katalin; Glant, Tibor T; Szekanecz, Zoltán

2014-03-01

The involvement of autoreactive T cells in the pathogenesis of rheumatoid arthritis (RA) as well as in autoimmune animal models of arthritis has been well established; however, unanswered questions, such as the role of joint-homing T cells, remain. Animal models of arthritis are superb experimental tools in demonstrating how T cells trigger joint inflammation, and thus can help to further our knowledge of disease mechanisms and potential therapies. In this Review, we discuss the similarities and differences in T-cell subsets and functions between RA and mouse arthritis models. For example, various T-cell subsets are involved in both human and mouse arthritis, but differences might exist in the cytokine regulation and plasticity of these cells. With regard to joint-homing T cells, an abundance of synovial T cells is present in humans compared with mice. On the other hand, local expansion of type 17 T-helper (TH17) cells is observed in some animal models, but not in RA. Finally, whereas T-cell depletion therapy essentially failed in RA, antibody targeting of T cells can work, at least preventatively, in most arthritis models. Clearly, additional human and animal studies are needed to fill the gap in our understanding of the specific contribution of T-cell subsets to arthritis in mice and men.

A fiducial skull marker for precise MRI-based stereotaxic surgery in large animal models.

Science.gov (United States)

Glud, Andreas Nørgaard; Bech, Johannes; Tvilling, Laura; Zaer, Hamed; Orlowski, Dariusz; Fitting, Lise Moberg; Ziedler, Dora; Geneser, Michael; Sangill, Ryan; Alstrup, Aage Kristian Olsen; Bjarkam, Carsten Reidies; Sørensen, Jens Christian Hedemann

2017-06-15

Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical and subcortical anatomical differences. 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-sulfate solution or MRI-visible paste from a commercially available cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. The use of skull bone based fiducial markers gives high precision for both targeting and evaluation of stereotaxic systems. There are no metal artifacts and the fiducial is easily removed after surgery. The fiducial marker can be used as a very precise reference point, either for direct targeting or in evaluation of other stereotaxic systems. Copyright © 2017 Elsevier B.V. All rights reserved.

The wild animal as a research animal

NARCIS (Netherlands)

Swart, JAA

2004-01-01

Most discussions on animal experimentation refer to domesticated animals and regulations are tailored to this class of animals. However, wild animals are also used for research, e. g., in biological field research that is often directed to fundamental ecological-evolutionary questions or to

Ethics and animal experimentation: what is debated?

Directory of Open Access Journals (Sweden)

Paixão Rita Leal

1999-01-01

Full Text Available The purpose of this article is to raise some points for an understanding of the contemporary debate over the ethics of using animals in scientific experiments. We present the various positions from scientific and moral perspectives establishing different ways of viewing animals, as well as several concepts like 'animal ethics', 'animal rights', and 'animal welfare'. The paper thus aims to analyze the importance and growth of this debate, while proposing to expand the academic approach to this theme in the field of health.

Ethics and animal experimentation: what is debated?

Directory of Open Access Journals (Sweden)

Rita Leal Paixão

Full Text Available The purpose of this article is to raise some points for an understanding of the contemporary debate over the ethics of using animals in scientific experiments. We present the various positions from scientific and moral perspectives establishing different ways of viewing animals, as well as several concepts like 'animal ethics', 'animal rights', and 'animal welfare'. The paper thus aims to analyze the importance and growth of this debate, while proposing to expand the academic approach to this theme in the field of health.

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

Directory of Open Access Journals (Sweden)

Spencer J. Ingley

2015-12-01

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

Ideal Experimental Rat Models for Liver Diseases.

Science.gov (United States)

Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

2011-05-01

There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

A New Tube Gastrostomy Model in Animal Experiments

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Atakan Sezer

2013-01-01

statistically significantly. Discussion: Here in we presented a novel and simple tube gastrostomy model in an experimental rat model in which rats had unrestrained movements. We believe that this new constructed tube gastrostomy model may be an alternative route for the experimental models in which orogastric route is unavailable to use.

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

Science.gov (United States)

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

Laboratory animal models for esophageal cancer

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Dhanya Venugopalan Nair

2016-11-01

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

Animal Models of Allergic Diseases

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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.

Animal Models of Diabetic Retinopathy: Summary and Comparison

Science.gov (United States)

Lo, Amy C. Y.

2013-01-01

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

Evaluation of protective effect of Aegle marmelos Corr. in an animal model of chronic fatigue syndrome.

Science.gov (United States)

Lalremruta, Vanphawng; Prasanna, Gurunath S

2012-05-01

To evaluate ethanolic extract of leaves of Aegle marmelos in an experimental animal model of chronic fatigue syndrome for potential therapeutic benefit. Age/weight-matched female Wistar albino rats were grouped into five groups. (Group I- V) (n = 8). Group I served as naïve control and II served as stress control. Except for group I animals, other group animals were subjected to forced swimming every day for 15 minutes to induce a state of chronic fatigue and simultaneously treated with ethanolic extract of Aegle marmelos (EEAM) 150 and 250 mg/kg b.w. and Imipramine (20 mg.kg b.w.), respectively. Duration of immobility, anxiety level and locomotor activity were assessed on day 1, 7, 14 and 21 followed by biochemical estimation of oxidative biomarkers at the end of the study. Treatment with EEAM (150 and 250 mg/kg b.w.) resulted in a statistically significant and dose dependent reduction (P immobility, reduction in anxiety and increase in locomotor activity. Dose dependent and significant reduction in LPO level and increase in CAT and SOD was observed in extract treated animals. The results are suggestive of potential protective effect of A. marmelos against experimentally induced CFS.

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.

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.

Experimental and mathematical modeling methods for the investigation of toxicological interactions

International Nuclear Information System (INIS)

El-Masri, Hisham A.

2007-01-01

While procedures have been developed and used for many years to assess risk and determine acceptable exposure levels to individual chemicals, most cases of environmental contamination can result in concurrent or sequential exposure to more than one chemical. Toxicological predictions of such combinations must be based on an understanding of the mechanisms of action and interaction of the components of the mixtures. Statistical and experimental methods test the existence of toxicological interactions in a mixture. However, these methods are limited to experimental data ranges for which they are derived, in addition to limitations caused by response differences from experimental animals to humans. Empirical methods such as isobolograms, median-effect principle and response surface methodology (RSM) are based on statistical experimental design and regression of data. For that reason, the predicted response surfaces can be used for extrapolation across dose regions where interaction mechanisms are not anticipated to change. In general, using these methods for predictions can be problematic without including biologically based mechanistic descriptions that can account for dose and species differences. Mechanistically based models, such as physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models, include explicit descriptions of interaction mechanisms which are related to target tissues levels. These models include dose-dependent mechanistic hypotheses of toxicological interactions which can be tested by model-directed experimental design and used to identify dose regions where interactions are not significant

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

Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

Energy Technology Data Exchange (ETDEWEB)

Vamathevan, Jessica J., E-mail: jessica.j.vamathevan@gsk.com [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)

2013-07-15

Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.

Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

International Nuclear Information System (INIS)

Vamathevan, Jessica J.; Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M.; Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli; Kenny, Steve; Brown, James R.; Huxley-Jones, Julie; Lyon, Jon; Haselden, John; Min, Jiumeng; Sanseau, Philippe

2013-01-01

Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns

Influence of different methods of internal bone fixation on characteristics of bone callus in experimental animals

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Gajdobranski Đorđe

2014-01-01

Full Text Available Introduction. Correct choice of osteosynthesis method is a very important factor in providing the optimal conditions for appropriate healing of the fracture. There are still disagreements about the method of stabilization of some long bone fractures. Critically observed, no method of fracture fixation is ideal. Each osteosynthesis method has both advantages and weaknesses. Objective. The objective of this study was to compare the results of the experimental application of three different internal fixation methods: plate fixation, intramedullary nail fixation and self-dynamisable internal fixator (SIF. Methods. A series of 30 animals were used (Lepus cuniculus as experimental animals, divided into three groups of ten animals each. Femoral diaphysis of each animal was osteotomized and fixed with one of three implants. Ten weeks later all animals were sacrificed and each specimen underwent histological and biomechanical testing. Results. Histology showed that the healing process with SIF was more complete and bone callus was more mature in comparison to other two methods. During biomechanical investigation (computerized bending stress test, it was documented with high statistical significance that using SIF led to stronger healing ten weeks after the operation. Conclusion. According to the results obtained in this study, it can be concluded that SIF is a suitable method for fracture treatment.

MicroRNA regulation of TLRs in a post-influenza animal model

DEFF Research Database (Denmark)

Brogaard, Louise; Heegaard, Peter M. H.; Larsen, Lars Erik

in the post-IAV infected individual. Using the pig as an animal model, we have identified microRNAs (miRNAs) that are differentially expressed in lung tissue two weeks after challenge compared to uninfected controls, i.e. well after the infection has cleared. The role for differential expression of mi......RNA at this late time point remains unclear. We therefore seek to examine the potential involvement of miRNAs in the translational regulation of TLRs and associated proteins, thus contributing to the lowered responsiveness to bacterial TLR ligands at this late time point, making the individual vulnerable...... to secondary infections. Methods and outcome Pigs were experimentally challenged with a Danish reassortant IAV strain (A/sw/Denmark/12687/03(H1N2)). Lung tissue was harvested 14 days after challenge, as well as from uninfected control animals. Using RNAseq and high-throughput RT-qPCR, we quantified...

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.

Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models

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Apparecido N. Daniel

Full Text Available Eugenia caryophyllata, popular name "clove", is grown naturally in Indonesia and cultivated in many parts of the world, including Brazil. Clove is used in cooking, food processing, pharmacy; perfumery, cosmetics and the clove oil (eugenol have been used in folk medicine for manifold conditions include use in dental care, as an antiseptic and analgesic. The objective of this study was evaluated the anti-inflammatory and antinociceptive activity of eugenol used for dentistry purposes following oral administration in animal models in vivo. The anti-inflammatory activity of eugenol was evaluated by inflammatory exudates volume and leukocytes migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. The antinociceptive activity was evaluated using the acetic acid-induced writhing and hot-plate tests in mice. Eugenol (200 and 400 mg/kg reduced the volume of pleural exudates without changing the total blood leukocyte counts. At dose of 200 mg/kg, eugenol significantly inhibited carrageenan-induced edema, 2-4 h after injection of the flogistic agent. In the hot-plate test, eugenol administration (100 mg/kg showed unremarkable activity against the time-to-discomfort reaction, recorded as response latency, which is blocked by meperidine. Eugenol at doses of 50, 75 and 100 mg/kg had a significant antinociceptive effect in the test of acetic-acid-induced abdominal writhing, compared to the control animals. The data suggest that eugenol possesses anti-inflammatory and peripheral antinociceptive activities.

Th17 in Animal Models of Rheumatoid Arthritis

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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.

Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome

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Olufunsho Awodele

2015-04-01

Full Text Available Background: National Agency for Food and Drugs Administration and Control (NAFDAC, which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg of gentamicin on kidney using animal models. Methods: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. Results: Significant increase (p ≤ 0.001 in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001 elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. Conclusion: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.

Animal Cancer Models of Skeletal Metastasis

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Catherine Hibberd

2013-01-01

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

The relevance of animal experimental results for the assessment of radiation genetic risks in man

International Nuclear Information System (INIS)

Stephan, G.

1981-01-01

No suitable data are available from man for the quantitative assessment of genetic radiation risk. Therefore, the results from experiments on animals must be utilized. Two hypotheses are presented here in drawing analogical conclusions from one species to another. Although the extrapolation of results from animal experiments remains an open question, the use of experimental results from mice seems to be justified for an assessment of the genetic radiation risk in man. (orig.) [de

Animal in vivo models of EBV-associated lymphoproliferative diseases: special references to rabbit models.

Science.gov (United States)

Hayashi, K; Teramoto, N; Akagi, T

2002-10-01

Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on our two newly-developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82-89%) during 2-5 months. EBV-DNA was detected in peripheral blood by PCR from 2 days after oral inoculation, while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, during 22-105 days. Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens.

Lanchester's attrition models and fights among social animals

OpenAIRE

Eldridge S. Adams; Michael Mesterton-Gibbons

2003-01-01

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

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

Animal models of obesity and diabetes mellitus

DEFF Research Database (Denmark)

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

2018-01-01

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

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract

OpenAIRE

Bosmans, Joanna W. A. M.; Moossdorff, Martine; Al-Taher, Mahdi; van Beek, Lotte; Derikx, Joep P. M.; Bouvy, Nicole D.

2016-01-01

Purpose This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. Methods PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower...

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.

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.