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Sleep apnea in mice: a useful animal model for study of SIDS?
Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest
Akira Nakamura; Tomoyuki Kuwaki
Sleep apnea in mice: a useful animal model for study of SIDS?
Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest
Akira Nakamura; Tomoyuki Kuwaki
Standardization of the outbred BALB/c mice as a suitable animal model for Besnoitia caprae studies.
The Apicomplexan parasite Besnoitia caprae infects wild and domestic goats. Knowledge on Besnoitia caprae specially an optimized animal model is sparse. Experimental infections with tachyzoites of BC-Pars obtained from BALB/c mice were conducted in outbred mice to determine the infectivity and LD50 of Besnoitia caprae. Six groups of five mice were intraperitoneally infected with 12.5?×?10(3), 25?×?10(3), 5?×?10(4), 1?×?10(5) and 2?×?10(5) tachyzoites and a control inoculum of DMEM, respectively. Although morbidity and mortality were observed in all groups, two mice in the 12.5?×?10(3) group showed alopecia and skin lesions on 60 days post-infection (DPI). Histopathological and molecular examination of skins confirmed B. caprae infection. The LD50 was calculated as 25?×?10(3.2) tachyzoites per mouse. The results indicate that outbred BALB/c mice can be used as a suitable model of besnoitiosis and to screen candidate treatments and to test the efficacy of vaccines for besnoitiosis. PMID:21744111
Namazi, Fatemeh; Namavari, Mohamad Mehdi; Rahimi, Ebrahim; Lotfi, Mohsen; Tahamtan, Yahya
The role of hair in swimming of laboratory mice: implications for behavioural studies in animals with abnormal hair
Summary Animal swimming tests, such as the forced swim test, are extensively used in biomedical research to study rodent behaviour. Hair and skin exposed to water may be an important factor affecting the performance in this test. Since various hair and skin abnormalities are not uncommon in genetically modified or drug-treated laboratory animals, this test may be inappropriate for these
A V Kalueff; P Tuohimaa
Are NCAM deficient mice an animal model for schizophrenia?
Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we studied social interaction and attention of NCAM null mutant (NCAM?/?) mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM?/? mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three—compartment—box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM?/? mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.
Albrecht, Anne; Stork, Oliver
Mice examined in Animal Laboratory of Lunar Receiving Laboratory
NASA Technical Reports Server (NTRS)
Landrum Young (seated), Brown and Root-Northrup, and Russell Stullken, Manned Spacecraft Center, examine mice in the Animal laboratory of the Lunar Receiving Laboratory which have been inoculated with lunar sample material. wish for peace for all mankind. astronauts will be released from quarantine on August 11, 1969. Donald K. Slayton (right), MSC Director of Flight Crew Operations; and Lloyd Reeder, training coordinator.
Big mice die young but large animals live longer
It has been known for millennia that large animals live longer, inspiring numerous theories of aging. For example, elephants and humans live longer than mice, which in turn live longer than worms and flies. The correlation is not perfect, with many explainable exceptions, but it is still obvious. In contrast, within each species (e.g., mice and some other mammals) small body size is associated with longevity and slow aging. The concept that aging (and age-related diseases) is an aimless continuation of developmental growth, a hyperfunction driven by the same nutrient-sensing and growth-promoting pathways such as MTOR, may explain this longstanding paradox.
Blagosklonny, Mikhail V.
VI. Animal Transmission Studies
The Cyprus strain of bluetongue virus was successfully transmitted through six passages and the Station strain through one passage in calves. Although the animals developed no visible evidence of infection, viremia as shown by both passage and fluorescent antibody examination of infected foetal bovine kidney culture, and by serological conversion was nevertheless demonstrated. No enhancement of virulence for calves or sheep was shown following bovine passage. A ewe inoculated in late pregnancy with blood drawn from a calf 59 days after its infection, gave birth to a lamb from whose blood the virus was isolated. Significant complement-fixation titres persisted for at least 200 days.
Gray, D. P.; Willis, N. G.; Girard, A.; Ruckerbauer, G. M.; Boulanger, P.; Bannister, G. L.
Toward an Animal Model for Antisocial Behavior: Parallels Between Mice and Humans
The goal of this article is to examine whether mouse lines genetically selected for short and long attack latencies are good animal models for antisocial behavior in humans. To this end, we compared male Short and Long Attack Latency mice (SAL and LAL, respectively) with the extremes of the Dunedin Multidisciplinary Health and Development Study (men who persistently displayed antisocial
Frans Sluyter; Louise Arseneault; Terrie E. Moffitt; Alexa H. Veenema; Sietse de Boer; Jaap M. Koolhaas
Radon Inhalation Studies in Animals.
National Technical Information Service (NTIS)
This report highlights the more recent animal data from the two US studies (UR and PNL) and the French (COGEMA) study. A major report, which particularly addressed the early, acute, radon-toxicity studies, concluded (as did an earlier Federal Radiation Co...
F. T. Cross
SCID Mice Transplanted With Human Cells as Small Animal Models in AIDS Research
The progress in AIDS research has been hampered by the lack of a small and practical animal model susceptible to HIV infection,\\u000a suitable for a rapid testing of antiviral compounds and vaccines. Over the past 20 years, different attempts have been made\\u000a to develop various models for AIDS in mice. An ensemble of studies carried out in several laboratories during
Caterina Lapenta; Stefano M. Santini; Massimo Spada; Filippo Belardelli
NASA Technical Reports Server (NTRS)
The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.
Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.
NASA Technical Reports Server (NTRS)
The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.
Schatte, C.; Grindeland, R.; Callahan, P.; Funk, G.; Lencki, W.; Berry, W.
Mice with liver composed of human hepatocytes as an animal model for drug testing.
Conventionally, rodents, mostly mice and rats, have been utilized as animal models for studying drug metabolism and toxicity of new medicines. However, there have been two major problems inherent to these models. One is that there are species differences in major enzymes responsible for drug metabolisms and detoxification such as cytochrome P450 between rodents and humans, and the other is that human hepatitis viruses do not infect rodent livers, which hampers studies for anti-hepatitis virus drugs using these models. As an approach to overcome these intrinsic shortages, we devised a method to generate mice whose livers are mostly ( > 80%) repopulated with healthy human hepatocytes 7 years ago. Since then, these mice called simply chimeric mice or liver-humanized mice have been widely utilized among researchers in the areas for new drug developments, which, as a result, have proved that the chimeric mouse is a practical solution to solve the above two issues. The hitherto accumulated studies demonstrating the similarities of the chimeric mouse liver to the human crude liver are summarized and reviewed in the present article. In addition, there have been also studies that show us the presence of dissimilarities between them, such as human hepatocytes' manifestation of hyperplasia in mouse liver and their steatotic alterations when the mice are maintained for > 50 days post-transplantation. These dissimilarities between them are also reviewed in details, considering that the information of the similarities and the dissimilarities is quite useful to researchers who utilize chimeric mice as a drug discovery tool for correctly evaluating the obtained results. PMID:22023259
Yoshizato, Katsutoshi; Tateno, Chise; Utoh, Rie
Animal imaging studies of potential brain damage
NASA Astrophysics Data System (ADS)
To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.
Gatley, S. J.; Vazquez, M. E.; Rice, O.
Sjögren's syndrome: studying the disease in mice
Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by inflammation of exocrine tissues accompanied by\\u000a a significant loss of their secretory function. Clinical symptoms develop late and there are no diagnostic tests enabling\\u000a early diagnosis of SS. Thus, particularly to study these covert stages, researchers turn to studying animal models where mice\\u000a provide great freedom for genetic manipulation and
Nicolas Delaleu; Cuong Q Nguyen; Ammon B Peck; Roland Jonsson
Developmental and reproductive toxicity of inorganic arsenic: Animal studies and human concerns
Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits).
Mari S. Golub; Michael S. Macintosh; Nikki Baumrind
Human SCARB2 Transgenic Mice as an Infectious Animal Model for Enterovirus 71
Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-?, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.
Lin, Yi-Wen; Yu, Shu-Ling; Shao, Hsiao-Yun; Lin, Hsiang-Yin; Liu, Chia-Chyi; Hsiao, Kuang-Nan; Chitra, Ebenezer; Tsou, Yueh-Liang; Chang, Hsuen-Wen; Sia, Charles; Chong, Pele; Chow, Yen-Hung
Update on animal models of diabetic retinopathy: from molecular approaches to mice and higher mammals
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the major causes of blindness worldwide. The pathogenesis of DR has been investigated using several animal models of diabetes. These models have been generated by pharmacological induction, feeding a galactose diet, and spontaneously by selective inbreeding or genetic modification. Among the available animal models, rodents have been studied most extensively owing to their short generation time and the inherited hyperglycemia and/or obesity that affect certain strains. In particular, mice have proven useful for studying DR and evaluating novel therapies because of their amenability to genetic manipulation. Mouse models suitable for replicating the early, non-proliferative stages of the retinopathy have been characterized, but no animal model has yet been found to demonstrate all of the vascular and neural complications that are associated with the advanced, proliferative stages of DR that occur in humans. In this review, we summarize commonly used animal models of DR, and briefly outline the in vivo imaging techniques used for characterization of DR in these models. Through highlighting the ocular pathological findings, clinical implications, advantages and disadvantages of these models, we provide essential information for planning experimental studies of DR that will lead to new strategies for its prevention and treatment.
Robinson, Remya; Barathi, Veluchamy A.; Chaurasia, Shyam S.; Wong, Tien Y.; Kern, Timothy S.
Animal model of silent myocarditis in athymic mice.
To clarify the role of the immune system in the development of myocarditis, BALB/c-nu/nu mice (group 1), BALB/c-nu/+ mice (group 2), BALB/c-nu/nu mice injected with 5 X 10(7) spleen cells from BALB/c-nu/+ mice (group 3), and BALB/c-nu/nu mice injected with 5 X 10(7) spleen cells from BALB/c-nu/+ mice treated with rat anti-Thy-1.2 monoclonal antibody with complement (group 4) were inoculated with encephalomyocarditis virus. There were no significant differences in the incidence of myocarditis among the four groups. Virus titrations of the heart and serum neutralising antibody titres in the four groups did not show any significant differences. Fifty two per cent (26/50) of group 2 and 43% (20/46) of group 3 died on days 9-15, when congestive heart failure developed. Only 9% (5/54) of group 1 and 8% (1/12) of group 4, however, died on days 9-15. Pathological examination confirmed congestive heart failure in groups 2 and 3 but not in groups 1 and 4. Dilatation of the ventricular cavities, pleural effusion, ascites, and congestion of the lungs and liver were present in groups 2 and 3 but not in groups 1 and 4. Cellular infiltration and myocardial necrosis were severe in groups 2 and 3 but minimal in groups 1 and 4. Thus the severity of myocarditis may be regulated by T cells. So-called silent myocarditis seen in clinical settings may be similar to myocarditis in BALB/c-nu/nu mice. PMID:3024835
Kishimoto, C; Kuribayashi, K; Masuda, T; Tomioka, N; Kawai, C
Video database system for studying animal behavior
NASA Astrophysics Data System (ADS)
Classification of farm animal behaviors are based upon oral or written descriptions of the activity that an animal is engaged in. The quantification of animal behavior for research requires that an individual recognize and code the behavior of the animal under study. The classification of these behaviors can be subjective and may differ among observers. Illustrated guides to animal behavior do not convey the motion associated with most behaviors. Video based guides offer a subjective method of quantifying behaviors with real time demonstrations of the components that make up a behavior. In this paper, we propose an animal behavior video database system which can automatically extract animal motion information from the input animal activity video clip by a multi-object tracking and reasoning system. The extracted information is then analyzed and described using a set of standard animal behavior terms we are developing. The behavior description is used to automatically annotate the given video clip, and serves as the content-based index. The user of the system is able to use a keywork description of the behavior to retrieve the corresponding video object. The intended applications of the system are animal and veterinary science education, and animal behavior research. The prototype system is built for swine and will be extended to other farm animal species.
Jiang, Haitao; Dailey, Jeffery W.
Chimeric mice with a humanized liver as an animal model of troglitazone-induced liver injury.
Troglitazone (Tro) is a thiazolidinedione antidiabetic drug that was withdrawn from the market due to its association with idiosyncratic severe liver injury. Tro has never induced liver injury in experimental animals in vivo. It was assumed that the species differences between human and experimental animals in the pharmaco- or toxicokinetics of Tro might be associated with these observations. In this study, we investigated whether a chimeric mouse with a humanized liver that we previously established, whose replacement index with human hepatocytes is up to 92% can reproduce Tro-induced liver injury. When the chimeric mice were orally administered Tro for 14 or 23 days (1000mg/kg/day), serum alanine aminotransferase (ALT) was significantly increased by 2.1- and 3.6-fold, respectively. Co-administration of l-buthionine sulfoximine (10mM in drinking water), an inhibitor of glutathione (GSH) synthesis, unexpectedly prevented the Tro-dependent increase of ALT, which suggests that the GSH scavenging pathway will not be involved in Tro-induced liver injury. To elucidate the mechanism of the onset of liver injury, hepatic GSH content, the level of oxidative stress markers and phase I and phase II drug metabolizing enzymes were determined. However, these factors were not associated with Tro-induced liver injury. An immune-mediated reaction may be associated with Tro-induced liver toxicity in vivo, because the chimeric mouse is derived from an immunodeficient SCID mouse. In conclusion, we successfully reproduced Tro-induced liver injury using chimeric mice with a humanized liver, which provides a new animal model for studying idiosyncratic drug-induced liver injury. PMID:22902350
Kakuni, Masakazu; Morita, Mayu; Matsuo, Kentaro; Katoh, Yumiko; Nakajima, Miki; Tateno, Chise; Yokoi, Tsuyoshi
Arsenite cocarcinogenesis: an animal model derived from genetic toxicology studies.
Although epidemiologic evidence shows an association between inorganic arsenic in drinking water and increased risk of skin, lung, and bladder cancers, no animal model for arsenic carcinogenesis has been successful. This lack has hindered mechanistic studies of arsenic carcinogenesis. Previously, we and others found that low concentrations (< or =5 microm) of arsenite (the likely environmental carcinogen), which are not mutagenic, can enhance the mutagenicity of other agents, including ultraviolet radiation (UVR) and alkylating agents. This enhancing effect appears to result from inhibition of DNA repair by arsenite, but not via inhibition of DNA repair enzymes. Rather, low concentrations of arsenite disrupt p53 function and upregulate cyclin D1. Failure to find an animal model for arsenic carcinogenesis might be because arsenite is not a carcinogen per se but acts as an enhancing agent (cocarcinogen) with a genotoxic partner. We tested this hypothesis with solar UVR in hairless but immunocompetent Skh1 mice. Mice were given 10 mg/L sodium arsenite in drinking water (or not) and irradiated with 1.7 KJ/m(2) solar UVR 3 times weekly. As expected, no tumors appeared in any organs in control mice or in mice given arsenite alone. After 26 weeks irradiated mice given arsenite had a 2.4-fold increase in skin tumor yield compared with mice given UVR alone. The tumors were mostly squamous cell carcinomas, and those occurring in mice given UVR plus arsenite were much larger and more invasive. These results are consistent with the hypothesis that arsenic acts as a cocarcinogen with a second (genotoxic) agent by inhibiting DNA repair and/or enhancing positive growth signaling. Skin cancers in populations drinking water containing arsenic may be caused by the enhancement by arsenic compounds of carcinogenesis induced by UVR (or other environmental agents). It is possible that lung and bladder cancers associated with arsenic in drinking water may also require a carcinogenic partner.
Rossman, Toby G; Uddin, Ahmed N; Burns, Fredric J; Bosland, Maarten C
Animal models of physiologic markers of male reproduction: genetically defined infertile mice.
The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of our investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, we investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. We propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.
Chubb, C
From dummies to animations: a review of computer-animated stimuli used in animal behavior studies
Traditionally, studies that explored animal communication have been directed towards the observation of natural interactions\\u000a between individuals. Over the years, researchers have long championed the use of artificial stimuli in place of natural ones\\u000a in behavioral experiments to precisely control what the observers get to see or experience. The employment of diverse techniques\\u000a to stage animal interactions has provided an
Kevin L. Woo; Guillaume Rieucau
Genetically engineered mice as animal models for NIDDM
Genetically engineered animals carrying defined alterations in their genome can represent invaluable tools for better understanding complex polygenic diseases such as non-insulin-dependent diabetes mellitus (NIDDM) at the molecular level. The structure or expression of a number of genes potentially involved in insulin action or pancreatic ?-cell function have recently been altered in the mouse using transgenic or gene-targeting approaches. The
Rajiv L Joshi; Betty Lamothe; Danielle Bucchini; Jacques Jami
Animal behaviour, animal welfare and the scientific study of affect
Many questions about animal welfare involve the affective states of animals (pain, fear, distress) and people look to science to clarify these issues as a basis for practices, policies and standards. However, the science of the mid twentieth century tended to be silent on matters of animal affect for both philosophical and methodological reasons. Philosophically, under the influence of Positivism
David Fraser
Creation of "Humanized" Mice to Study Human Immunity
"Humanized" mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strains such as NOD-scid IL2r? null mice that lack the IL-2 receptor common gamma chain. These stocks of mice lack adaptive immune function, display multiple defects in innate immunity, and support heightened levels of human hematolymphoid engraftment. Humanized mice can support studies in many areas of immunology, including autoimmunity, transplantation, infectious diseases, and cancer. These models are particularly valuable in experimentation where there is no appropriate small animal model of the human disease, as in the case of certain viral infections. This unit details the creation of humanized mice by engraftment of immunodeficient mice with hematopoietic stem cells or peripheral blood mononuclear cells, provides methods for evaluating engraftment, and discusses considerations for choosing the appropriate model system to meet specific goals.
Pearson, Todd; Greiner, Dale L.; Shultz, Leonard D.
Animal carcinogenicity studies: 3. Alternatives to the bioassay.
Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly difficult any attempts to accurately extrapolate animal data in order to predict carcinogenic hazards to humans. Proposed modifications to the conventional bioassays have included the elimination of mice as a second species, and the use of genetically-altered or neonatal mice, decreased study durations, initiation-promotion models, the greater incorporation of toxicokinetic and toxicodynamic assessments, structure-activity relationship (computerised) systems, in vitro assays, cDNA microarrays for detecting changes in gene expression, limited human clinical trials, and epidemiological research. The potential advantages of non-animal assays when compared to bioassays include the superior human specificity of the results, substantially reduced time-frames, and greatly reduced demands on financial, personnel and animal resources. Inexplicably, however, the regulatory agencies have been frustratingly slow to adopt alternative protocols. In order to decrease the enormous cost of cancer to society, a substantial redirection of resources away from excessively slow and resource-intensive rodent bioassays, into the further development and implementation of non-animal assays, is both strongly justified and urgently required. PMID:16522149
Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan
Satellite animal tracking feasibility studies
NASA Technical Reports Server (NTRS)
A study was initiated in Tsavo National Park to determine movements and home ranges of individual elephants and their relations to overall distribution patterns and environmental factors such as rainfall. Methods used were radio tracking and observations of visually identifiable individuals. Aerial counts provided data on overall distribution. Two bulls and two cows were radio-tagged in Tsavo West and two bulls and four cows in Tsavo East, providing home range and movement data. The movements of individuals were useful in interpreting relatively major shifts in elephant distribution. Results point to the following preliminary conclusions: (1) elephants in the Tsavo area undertook long distance movements in fairly direct response to localized rainfall; (2) a subdivision of the overall population into locally distinct units may exist during the dry season but did not occur after significant rainfall; and (3) food appears to be the primary factor governing movements and distribution of elephants in the area.
Buechner, H. K.
An animal model of age-related macular degeneration in senescent Ccl2- or Ccr2-deficient mice
The study and treatment of age-related macular degeneration (AMD), a leading cause of blindness, has been hampered by a lack of animal models. Here we report that mice deficient either in monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1) or its cognate C-C chemokine receptor-2 (Ccr-2) develop cardinal features of AMD, including accumulation of lipofuscin in and drusen beneath the
Akshay Anand; Stefan Fernandez; Eiji Sakurai; Bert C Lynn; William A Kuziel; Barrett J Rollins; Balamurali K Ambati; Jayakrishna Ambati
Thermal latency studies in opiate-treated mice
Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves) tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus studies at 1-5 hours and 1-5 days to test acute and extended release preparations of buprenorphine. Results: Hargreaves testing had limited value at 1-5 hours because mice can have an obtunded response to opiate therapy. Tail-flick studies with restrained mice are not affected by the initial locomotor stimulation. Discussion: The present report describes a simple restraint system for mice. The utility of the system is demonstrated by examining the efficacy of acute and extended release buprenorphine injections in Balb/c and Swiss mice. Conclusion: Standardized tail-flick testing provides a sensitive robust method to monitor opiate activity in mice.
Schildhaus, Noam; Trink, Eliana; Polson, Chirs; DeTolla, Louis; Tyler, Betty M.; Jallo, George I.; Tok, Sino; Guarnieri, Michael
Effects of sevoflurane general anesthesia: immunological studies in mice
Based on the immunomodulatory effects of anesthesia and surgery, a study was undertaken to assess the effect of sevoflurane anesthesia on the immune system in a murine model without surgery.Adult male mice were anesthetized with 3% sevoflurane (1.2 minimal alveolar concentration, MAC) in oxygen for 40 min, whereas nontreated animals served as controls. After sevoflurane anesthesia, peripheral blood leukocyte counts,
N. R Puig; P Ferrero; M. L Bay; G Hidalgo; J Valenti; N Amerio; G Elena
Hot Air Coagulation: An Animal Study
Aerothermotherapy with a Leister® hot air coagulator was tested in a simulated operation field followed by a prospective double-blind animal pilot study to examine hemostasis and tissue reactions. Two symmetrical incisions were made on the back of 5 rabbits. One of the two wounds was randomised to aerothermotherapy. The temperature rise in the wound was registered by thermistors. No wound
C. Rude; O. V. Rasmussen; C. Rygaard; F. Haslev
SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects.
Defects of the mitochondrial genome are important causes of disease. Despite major advances in our investigation of patients, there is no effective therapy. Progress in this area is limited by the absence of any animal models in which we can evaluate treatment. To develop such a model we have injected human myoblasts into the tibialis anterior of SCID mice after inducing necrosis. After injection of normal human myoblasts, regenerating fibers expressed human beta-spectrin, confirming they were derived from fusion of human myoblasts. The stability of the muscle fibers was inferred by demonstrating the formation of motor end plates on the regenerating fibers. In addition, we show the presence of human cytochrome c oxidase subunit II, which is encoded by the mitochondrial genome, in the regenerated fibers. After injection of human myoblasts containing either the A8344G or the T8993C heteroplasmic mitochondrial DNA mutations, human beta-spectrin positive fibers were found to contain the mutation at a similar level to the injected myoblasts. These studies highlight the potential value of this model for the study of mitochondrial DNA defects.
Clark, K M; Watt, D J; Lightowlers, R N; Johnson, M A; Relvas, J B; Taanman, J W; Turnbull, D M
Mice Drawer System: a Long Duration Animal Experiment on the International Space Station
NASA Astrophysics Data System (ADS)
Mice represent one of the most important animal models for biomedical research. In the past decade mice have been used as surrogates to understand physiological adaption and its under-lying mechanisms to orbital spaceflight. A breakthrough in this field has been achieved with the launch of MDS experiment inside Shuttle Discovery (mission STS-128) on August 28, 2009 at 23:58 EST, and its re-entry to earth by Shuttle Atlantis (mission STS-129) on November 27 2009 at 9:47 EST, marking this as the first long duration animal experiment on the Interna-tional Space Station (ISS). This presentation will provide the life history and milestones starting from the project brainstorm to the post-ground activities of the recent MDS payload mission. The Italian Space Agency (ASI) initiated and coordinated this multi-disciplinary project by focusing on five areas: the development of a multi-purpose automated payload by industry; bio-compatibility tests of subsystems throughout various critical phases of the payload development by researchers, development of a ground segment to interface with NASA Payload Operations Center and three different geographically distributed Italian Operations Centers; establishment of an international tissue sharing program; specialized bio-specimen intercontinental shipment. With close collaboration with NASA, activities such as pre-flight payload acceptance, animal preparation, in-flight crew intervention and re-entry animal recovery were smoothly and swiftly accomplished.
Cotronei, Vittorio; Liu, Yi; Pignataro, Salvatore
An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity.
Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1-infected humanized mouse model generated by intra-bone marrow injection of human CD133(+) stem cells into NOD/Shi-scid/IL-2R?c null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD4(+) human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD25(-) and CD25(+) CD4 T cells with identical proviral integration sites; however, a limited number of CD25(+)-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1-specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1-infected cells. Thus, the HTLV-1-infected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates. PMID:24196073
Tezuka, Kenta; Xun, Runze; Tei, Mami; Ueno, Takaharu; Tanaka, Masakazu; Takenouchi, Norihiro; Fujisawa, Jun-ichi
Neutral aminoaciduria in cystathionine ?-synthase-deficient mice, an animal model of homocystinuria.
The kidney is one of the major loci for the expression of cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CTH). While CBS-deficient (Cbs(-/-)) mice display homocysteinemia/methioninemia and severe growth retardation, and rarely survive beyond the first 4 wk, CTH-deficient (Cth(-/-)) mice show homocysteinemia/cystathioninemia but develop with no apparent abnormality. This study examined renal amino acid reabsorption in those mice. Although both 2-wk-old Cbs(-/-) and Cth(-/-) mice had normal renal architecture, their serum/urinary amino acid profiles largely differed from wild-type mice. The most striking feature was marked accumulation of Met and cystathionine in serum/urine/kidney samples of Cbs(-/-) and Cth(-/-) mice, respectively. Levels of some neutral amino acids (Val, Leu, Ile, and Tyr) that were not elevated in Cbs(-/-) serum were highly elevated in Cbs(-/-) urine, and urinary excretion of other neutral amino acids (except Met) was much higher than expected from their serum levels, demonstrating neutral aminoaciduria in Cbs(-/-) (not Cth(-/-)) mice. Because the bulk of neutral amino acids is absorbed via a B(0)AT1 transporter and Met has the highest substrate affinity for B(0)AT1 than other neutral amino acids, hypermethioninemia may cause hyperexcretion of neutral amino acids. PMID:24761004
Akahoshi, Noriyuki; Kamata, Shotaro; Kubota, Masashi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Yamazaki, Chiho; Yoshida, Yuka; Yamada, Hidenori; Ishizaki, Yasuki; Suematsu, Makoto; Kasahara, Tadashi; Ishii, Isao
Animal studies of charged particle-induced carcinogenesis.
The distribution of energy deposition in cells and tissues by high-charge, high-energy (HZE) nuclei differs considerably from that of low linear energy transfer (LET) radiation, raising concerns that charged particle exposure may be more efficient in inducing radiogenic cancers or may induce a different spectrum of tumors. The authors have performed a review of charged particle carcinogenesis in animals with the following observations. A limited number of animal studies with carcinogenesis endpoints have been performed to evaluate the effectiveness of HZE ions. These include the induction of skin and mammary tumors in the rat and Harderian gland tumors, acute myeloid leukemia (AML), and hepatocellular carcinomas in the mouse. In general, high relative biological effectiveness (RBE) has been reported for solid tumor induction. RBE dependence on HZE radiation quality has been most extensively characterized in studies of mouse Harderian gland tumorigenesis. In this model, the RBE increases with LET and plateaus in the 193-953 keV ?m(-1) range. Unlike the results of solid tumor studies, a leukemogenesis study found 1 GeV nucleon(-1) 56Fe ions no more efficient than gamma-rays for AML induction. No novel tumor types have been observed in HZE irradiated animals as compared with those that occur spontaneously or following low-LET radiation exposures. Genetic background of the irradiated animals is critical; the tumor types induced in HZE irradiated mice depend on their strain background, and the incidence of HZE ion-induced mammary carcinogenesis in the rat is also strain dependent. PMID:23032886
Bielefeldt-Ohmann, Helle; Genik, Paula C; Fallgren, Christina M; Ullrich, Robert L; Weil, Michael M
NSDL National Science Digital Library
Animation is making a splash with the recent box office hit, Shrek 2. This Topic in Depth explores how animation works, it's history and the entertaining as well as academic applications of animation. The first website provides a basic overview of digital cinema (1). More information on animation can be found on the second website (2). Digital Media FX provides this history (3 ) of animation. The Library of Congress has also put together a nice website (4 ) with some historical artifacts that for demonstrating a "a variety of elements that go into the creative process of developing and interpreting animated motion pictures." The fourth website provides an extensive list of online resources and academic uses for animation such as Chemistry, Evolution, Genetics, and Physics. (5 ). This fifth website posts the winners of the 2004 Character Animation Technologies competition (6 ). And finally, Slashdot has a nice expose on the Mathematics of Futurama (7).
Study on DBS device for small animals.
Although deep brain stimulation (DBS) therapy has been achieved, fine tuning on the operational parameters and the equipment are needed in order to make the stimulation treatment more applicable. Thus, the purpose of this study is to design and produce a deep brain stimulation device for DBS experiments for small animals (e.g. rats). Physical size, durability, cost of device and convenience of operation are the major focuses in this study. The designed pulse generator can produce pulses with adjustable frequencies, pulse widths and amplitudes. Telemetry and remote control of the system reduced the physical size of the implant component. Battery voltage measurement and electrode impedance measurement justified the values of parameters applied for stimulation. Power consumption is low enough and test results show it is expected to work for more than three months when using typical pulse parameters. Finally, we use the device on the DBS experiment of rats. The results prove that the design of the device can fulfill the requirements for deep brain stimulation in animal experiments. PMID:22255893
Qian, Xing; Hao, Hongwei; Ma, Bozhi; Wen, Xiongwei; Li, Luming
\\u000a Ah, animation! Where would we be without the likes of Disney, Warner Bros., Walter Lanz, Hanna-Barbera, and dozens more like\\u000a them? For many people, animation is the reason to get involved with Flash as a creative outlet. This makes perfect sense, because Flash began life more than a decade ago\\u000a as an animation tool. Supplemental features like ActionScript, XML parsing,
Tom Green; David Stiller
ERIC Educational Resources Information Center
Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…
Tech Directions, 2008
Study of Dengue Virus Infection in SCID Mice Engrafted with Human K562 Cells
Here we report that severe combined immunodeficient (SCID) mice engrafted with human K562 cells (K562-SCID mice) can be used as an animal model to study dengue virus (DEN) infection. After intratumor injection into K562 cell masses of PL046, a Taiwanese DEN-2 human isolate, the K562-SCID mice showed neurological signs of paralysis and died at approximately 2 weeks postinfection. In addition
Mice Do Not Habituate to Metabolism Cage Housing-A Three Week Study of Male BALB/c Mice
The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.
Kalliokoski, Otto; Jacobsen, Kirsten R.; Darusman, Huda S.; Henriksen, Trine; Weimann, Allan; Poulsen, Henrik E.; Hau, Jann; Abelson, Klas S. P.
Animal models of anxiety disorders in rats and mice: some conceptual issues
Animal models can certainly be useful to find out more about the biological bases of anxiety disorders and develop new, more efficient pharmacological and/or behavioral treatments. However, many of the current "models of anxiety" in animals do not deal with pathology itself, but only with extreme forms of anxiety which are still in the normal, adaptive range. These models have certainly provided a lot of information on brain and behavioral mechanisms which could be involved in the etiology and physiopathology of anxiety disorders, but are usually not satisfactory when confronted directly with clinical syndromes. Further progress in this field will probably depend on the finding of endophenotypes which can be studied in both humans and animals with common methodological approaches. The emphasis should be on individual differences in vulnerability, which have to be included in animal models. Finally, progress will also depend on refining theoretical constructs from an interdisciplinary perspective, including psychiatry, psychology, behavioral sciences, genetics, and other neurosciences.
Steimer, Thierry
Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome
Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.
Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y.
A novel lung injury animal model using KL-6-measurable human MUC1-expressing mice.
KL-6, an epitope of MUC1 mucin expressed on type II pneumocytes and bronchiolar epithelia in humans, is a sensitive serum marker for interstitial pneumonia. However, an in vivo model for KL-6 has not been established because no KL-6 epitope is expressed in animals other than humans and apes. To investigate whether KL-6 is detectable in human MUC1-expressing (hMUC1-exp) mice and whether KL-6 level reflects the degree of lung injury, we examined serum and bronchoalveolar lavage fluid (BALF) levels of KL-6 and surfactant protein-D (SP-D) in either lipopolysaccharide (LPS)- or bleomycin (BLM)-induced lung injury models. KL-6 was expressed on type II pneumocytes and bronchiolar epithelial cells in naďve hMUC1-exp mice. Serum KL-6 levels in these mice were comparable to those in humans, and KL-6 levels in BALF were significantly higher than those in sera. In the LPS model, KL-6 levels in sera and BALF were slightly increased, although SP-D levels were markedly increased. During the inflammatory phase in the BLM model, KL-6 levels in sera were greatly increased, but those in BALF were decreased. Serum KL-6 levels were positively correlated with BALF albumin levels, a representative marker for increased the alveolar-capillary permeability. SP-D levels in sera and BALF were significantly increased compared to the corresponding levels in the LPS model. The increase in serum KL-6 levels appeared to be associated with the disruption of alveolar-capillary barrier after BLM-induced lung injury. This hMUC1-exp mouse can be used for assessment of KL-6 in vivo during lung injury. PMID:23410752
Sakai, Mizu; Kubota, Tetsuya; Ohnishi, Hiroshi; Yokoyama, Akihito
Animal carcinogenicity studies: 1. Poor human predictivity.
The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p < 0.0001). The IARC is a leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors. PMID:16522147
Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan
MOSFET assessment of radiation dose delivered to mice using the Small Animal Radiation Research Platform (SARRP).
The Small Animal Radiation Research Platform (SARRP) is a novel isocentric irradiation system that enables state-of-the-art image-guided radiotherapy research to be performed with animal models. This paper reports the results obtained from investigations assessing the radiation dose delivered by the SARRP to different anatomical target volumes in mice. Surgically implanted metal oxide semiconductor field effect transistors (MOSFET) dosimeters were employed for the dose assessment. The results reveal differences between the calculated and measured dose of -3.5 to 0.5%, -5.2 to -0.7%, -3.9 to 0.5%, -5.9 to 2.5%, -5.5 to 0.5%, and -4.3 to 0% for the left kidney, liver, pancreas, prostate, left lung, and brain, respectively. Overall, the findings show less than 6% difference between the delivered and calculated dose, without tissue heterogeneity corrections. These results provide a useful assessment of the need for tissue heterogeneity corrections in SARRP dose calculations for clinically relevant tumor model sites. PMID:21962005
Ngwa, Wilfred; Korideck, Houari; Chin, Lee M; Makrigiorgos, G Mike; Berbeco, Ross I
Students' Ideas about Animals: Results from a National Study.
ERIC Educational Resources Information Center
Explains a study that assesses students' ideas about animals. Evaluates textbooks and trade books according to the identifications and words they use. Discusses student responses from different grade levels on the classification of animals and identifying what is an animal. Summarizes the results of the study and makes recommendations on the…
Barman, Charles R.; Barman, Natalie S.; Cox, Mary Lou; Newhouse, Kay Berglund; Goldston, M. Jenice
A Study of Statistical Errors in MICE
NASA Astrophysics Data System (ADS)
The Muon Ionization Cooling Experiment (MICE) will measure ionization cooling from a beam of muons at the Rutherford Appleton Laboratory in the UK. The aim of MICE is to measure a fractional drop in emittance, due to ionization cooling, of order 10% for a range of emittances and momenta, to an accuracy of 1%. A greater understanding of the statistical (as well as systematic) errors on emittance measurement in MICE is paramount to meeting this goal. This paper describes a study aimed at exploiting the computing power of the Grid to determine the number of muons necessary to meet the scientific goals of MICE. In this study, tens of thousands of G4MICE Monte Carlo simulations were run to determine the scaling laws that govern the fractional change in emittance as a function of the number of muons (N) in the simulation. By varying random conditions, the standard deviation of these distributions was studied as a function of N. The results of the study indicate that, due to the effect of correlations, of order 105 muons are required to meet the goal of MICE for large emittance beams, without which 106 would be required.
Forrest, D.; Soler, F. J. P.
A Study of Statistical Errors in MICE
The Muon Ionization Cooling Experiment (MICE) will measure ionization cooling from a beam of muons at the Rutherford Appleton Laboratory in the UK. The aim of MICE is to measure a fractional drop in emittance, due to ionization cooling, of order 10% for a range of emittances and momenta, to an accuracy of 1%. A greater understanding of the statistical (as well as systematic) errors on emittance measurement in MICE is paramount to meeting this goal.This paper describes a study aimed at exploiting the computing power of the Grid to determine the number of muons necessary to meet the scientific goals of MICE. In this study, tens of thousands of G4MICE Monte Carlo simulations were run to determine the scaling laws that govern the fractional change in emittance as a function of the number of muons (N) in the simulation. By varying random conditions, the standard deviation of these distributions was studied as a function of N. The results of the study indicate that, due to the effect of correlations, of order 10{sup 5} muons are required to meet the goal of MICE for large emittance beams, without which 10{sup 6} would be required.
Forrest, D.; Soler, F. J. P. [University of Glasgow, Glasgow G12 8QQ (United Kingdom)
A study of animal companionship in a day hospice.
Attitudes to companion animals were surveyed among 50 patients and staff at a day care hospice. Dog visits were welcomed by all but two. Of the 37 patients studied, only seven had a companion animal, often their closest companion. Many more would like to keep an animal, but were prevented by age, frailty or accommodation restriction. PMID:8931070
Phear, D N
Phenomenology and the Study of Animal Behavior
Has the research on animal behavior anything to gain from phenomenology? And vice versa: has phenomenology something to learn from the different disciplines operating in this field, or is it a self-sufficing doctrine without any serious aspiration to look outside its immediate scope? After all, one might argue that it follows from the phenomenological reduction that the claims made by
Erika Ruonakoski
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.
Loria-Cervera, Elsy Nalleli; Andrade-Narvaez, Fernando Jose
Animal models for the study of leishmaniasis immunology.
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 × 10(2) and "high" 1 × 10(6)) 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. PMID:24553602
Loría-Cervera, Elsy Nalleli; Andrade-Narváez, Fernando José
Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments.
This study was to investigate a hypothesis that dietary restriction (DR) suppresses learning and memory impairments in dementia animal model SAMP8 mice. Four-week-old female SAMP8 mice were fed either ad libitum (AL) or fed restricted (40% of the food consumed by AL). Results showed that acetylcholine (ACh) levels in hippocampus at aged 12 months of age were 12% higher in DR than that of AL group. Dopamine (DA) and norepinephrine (NE) levels in cerebellum at 8 and 12 months of age were significantly higher (26~94% and 34~43%, respectively) in DR group than those in AL group. Serotonin (5-HT) levels in cerebellum at aged 12 months of age were markedly increased (~53%) in DR group. Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in cerebellum at 8 and 12 months of age were significantly increased (28~41% and 24~64%, respectively) in DR group compared with AL group. In addition, neurotransmitter-related enzymes, choline acetyltransferase (ChAT) and acetylchoinesterase (AChE) activities at 8 and 12 months of age were elevated (6~8% and 5~7%, respectively) in DR group. Monoamine oxidase-B (MAO-B) that catalyzes oxidative deamination in brain were suppressed by 7~10% in DR group. At aged 12 months of age, the generation of basal and induced reactive oxygen species (ROS) in brain significantly decreased by 20% in DR group compared with AL group. These results suggest that inhibitory effect of oxidative stress by DR may play a pivotal role in attenuating the age-related changes observed in dementia animal model SAMP8. PMID:11115807
Kim, D W; Choi, J H
A study in animal ethics in New Brunswick.
Society uses animals in ever-increasing numbers and ways, providing ethical challenges. Decisions about animal use are guided by the social consensus ethic towards animals. Because there is no clear social consensus ethic, these decisions are difficult. Society's ethic is changing and a "new ethic" towards animals is emerging. This study addressed the need to better understand society's ethics towards animals. Qualitative research methodology (focus groups) was used to study 7 different animal-interest groups. Qualitative data analysis was computer-aided. The group ethical position towards animals of its own group interest was determined for each group. The animal welfare, companion animal, and veterinary groups took Rollin's Position, a position based on both the Utilitarian and the Rights Principles; the farmer and trapper groups the Utilitarian/Land Ethic position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and preserving the integrity, stability, and beauty of the biotic community; the hunter group the Utilitarian/Judeo-Christian position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and having dominion over animals; and the naturalist group took Rollin's Position/Land Ethic. All these groups perceived medium to extreme ethical responsibility towards animals of their own group's interest that are used by others. The study showed that the predicted "new ethic" towards animals is in New Brunswick society and it is Rollin's Position.
Schneider, B J
Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals
Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.
Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L
Behavioural studies of MHC-congenic mice.
Behavioural studies of MHC-congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117-158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC-congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6-H-2bml and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6-H-2bml; and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms. PMID:10386391
Brown, R E; Schellinck, H M; Jagosh, J
A Comparative Approach To Animal Dissections (A Phylogenic Study)
NSDL National Science Digital Library
In this biology inquiry lab, students study evolutionary relationships by making observations of preserved animal specimens, developing a question, then investigating by dissecting the specimens provided.
A novel animal model for in vivo study of liver cancer metastasis
AIM: To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis. METHODS: Cell transplantation into mouse livers was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator (uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse line (uPA/SCID mice). Host mice were divided into two groups (A and B). Group A mice were transplanted with h-GCCs alone, and group B mice were transplanted with h-GCCs and h-hepatocytes together. The replacement index (RI), which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section, was estimated by measuring h-AFP and h-albumin concentrations in sera, respectively, as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections. RESULTS: The h-GCCs successfully engrafted, repopulated, and colonized the livers of mice in group A (RI = 22.0% ± 2.6%). These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures, which is a characteristics feature of gastric cancers. The serum h-AFP level reached 211.0 ± 142.2 g/mL (range, 7.1-324.2 g/mL). In group B mice, the h-GCCs and h-hepatocytes independently engrafted, repopulated the host liver, and developed colonies (RI = 12.0% ± 6.8% and 66.0% ± 12.3%, respectively). h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies. These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period. The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo. CONCLUSION: A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line. This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.
Fujiwara, Shinsuke; Fujioka, Hikaru; Tateno, Chise; Taniguchi, Ken; Ito, Masahiro; Ohishi, Hiroshi; Utoh, Rie; Ishibashi, Hiromi; Kanematsu, Takashi; Yoshizato, Katsutoshi
Vinyl chloride: inhalation teratology study in mice, rats and rabbits.
These studies evaluated the effects of inhaled vinyl chloride monomer (VCM) on mouse, rat and rabbit embryonal and fetal development. Groups of pregnant CF-1 mice, Sprague-Dawley rats and New Zealand white rabbits were exposed to 500 ppm VCM for 7 hr daily during the period of major organogenesis. Subsequently, other groups of mice were similarly exposed to 50 ppm VCM, and rats and rabbits were exposed to 2500 ppm. While maternal toxicity was observed, exposure to VCM did not cause significant embryonal or fetal toxicity and was not teratogenic in any of the three species at the concentrations tested. Simultaneous exposure of some of the pregnant animals to VCM by inhalation plus 15% ethanol in the drinking water resulted in toxic effects greater than those associated with exposure to VCM alone in the three species. The fetal effects observed were similar to those reported for these three species following administration of ethanol without VCM exposure.
John, J A; Smith, F A; Schwetz, B A
In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals
The current study was undertaken to investigate potential oncogenic functions of NanogP8, a tumor-specific retrogene homolog of Nanog (expressed in pluripotent cells), in transgenic animal models. To this end, human primary prostate tumor-derived NanogP8 was targeted to the cytokeratin 14 (K14) cellular compartment, and two lines of K14-NanogP8 mice were derived. The line 1 animals, expressing high levels of NanogP8, experienced perinatal lethality and developmental abnormalities in multiple organs, including the skin, tongue, eye, and thymus in surviving animals. On postnatal day 5 transgenic skin, for example, there was increased c-Myc expression and Ki-67+ cells accompanied by profound abnormalities in skin development such as thickened interfollicular epidermis and dermis and lack of hypodermis and sebaceous glands. The line 3 mice, expressing low levels of NanogP8, were grossly normal except cataract development by 4–6 mo of age. Surprisingly, both lines of mice do not develop spontaneous tumors related to transgene expression. Even more unexpectedly, high levels of NanogP8 expression in L1 mice actually inhibited tumor development in a two-stage chemical carcinogenesis model. Mechanistic studies revealed that constitutive NanogP8 overexpression in adult L1 mice reduced CD34+?6+ and Lrig-1+ bulge stem cells, impaired keratinocyte migration, and repressed the expression of many stem cell-associated genes, including Bmp5, Fgfr2, Jmjd1a, and Jun. Our study, for the first time, indicates that transgenically expressed human NanogP8 is biologically functional, but suggests that high levels of NanogP8 may disrupt normal developmental programs and inhibit tumor development by depleting stem cells.
Badeaux, Mark A; Jeter, Collene R; Gong, Shuai; Liu, Bigang; Suraneni, Mahipal V; Rundhaug, Joyce; Fischer, Susan M; Yang, Tao; Kusewitt, Donna; Tang, Dean G
ABSTRACT Transgenic animals are becoming,useful tools for pharmacological,studies. The use of transgenic technology raises two types of questions, "How are transgenic animals made?" and "What types of pharmacological,questions can be answered using transgenic technologies?" Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves
Li-Na Wei
Susceptibility of Mice to Vaginal Infection with Chlamydia trachomatis Mouse Pneumonitis Is Dependent on the Age of the Animal
Mice from three strains, BALB\\/c (H-2 d ), C3H (H-2 k ), and C57BL\\/6 (H-2 b ), ranging from 5 to 14 weeks of age, were inoculated intravaginally with different doses of the Chlamydia trachomatis mouse pneumonitis serovar. Vaginal swabs taken at weekly intervals showed that the percentage of animals with positive cultures and the number of inclusion-forming units recovered
? ?-Tocopherol on Liver Biochemistry of Endosulfan Intoxicated Mice: A Preliminary Study
The present study was designed to evaluate the protective role of ?-tocopherol (vit.E) against the toxic effects of chlorinated insecticide endosulfan. Forty male albino mice were used as mammalian model in this study. Animals were divided into 4 groups (ten animals each) on the basis of Vitamin-E treatment and endosulfan exposure, Vitamin treatment was started 15 days prior to 1st
Najma Arshad; Gulnaz Shabbir; Shahla Aleem; Muhammad Arshad
Mito-mice: animal models for mitochondrial DNA-based diseases
We have successfully produced 'Mito-mice' harbouring a pathogenic mtDNA mutation. We generated the mice by introducing mitochondria with a 4696 base-pair mtDNA deletion (? mtDNA4696) into mouse embryos. This deletion encompasses nucleotides 7759–12 454 and includes six tRNA genes and seven structural genes. In Mito-mice, the ? mtDNA4696 is transmitted maternally, and induces mitochondrial dysfunction in various tissues. Most of
Kazuto Nakada; Kimiko Inoue; Jun-Ichi Hayashi
Progress of genome wide association study in domestic animals
Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described.
Some Animal Models for the Study of Perinatal Asphyxia
Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered Ę?perfect' in reflecting the variety and complexity of human
Tonse N. K Raju
Study of antiseizure effects of Matricaria recutita extract in mice.
Matricaria recutita L. is a well-known medicinal plant that is suggested as being carminative, analgesic, and anticonvulsant in traditional medicine. In the present investigation the effect of hydro-methanolic percolated extract of this plant on seizure induced by picrotoxin was studied in male mice. This study was performed on animals pretreated with doses of 100, 200, and 300 mg/kg of extract or 40 mg/kg phenobarbital as the reference drug via intraperitoneal injection. After 20 min each animal received 12 mg/kg picrotoxin for induction of seizure. Latency of onset time of seizure, duration of seizure, death latency, and death rate were determined in experimental and control groups. The results showed that latency of the beginning time of seizure was increased in groups that were pretreated with different doses of extract. The most effective dose was 200 mg/kg (P < 0.05). In addition, this dose delayed the time of death in mice (P < 0.01). The extract had no effect on the death rate. The results indicate that the extract of M. recutita possesses suitable effects on seizure induced by picrotoxin, and more experiments are needed in this field. PMID:19723069
Heidari, M R; Dadollahi, Z; Mehrabani, M; Mehrabi, H; Pourzadeh-Hosseini, M; Behravan, E; Etemad, L
Scanning multiple mice in a small-animal PET scanner: Influence on image quality
To achieve high throughput in small-animal positron emission tomography (PET), it may be advantageous to scan more than one animal in the scanner's field of view (FOV) at the same time. However, due to the additional activity and increase of Poisson noise, additional attenuating mass, extra photon scattering, and radial or axial displacement of the animals, a deterioration of image
Françoise J. Siepel; Monique G. J. T. B. van Lier; Mu Chen; Jonathan A. Disselhorst; Antoi P. W. Meeuwis; Wim J. G. Oyen; Otto C. Boerman; Eric P. Visser
Gene Expression Changes in the Olfactory Bulb of Mice Induced by Exposure to Diesel Exhaust Are Dependent on Animal Rearing Environment
There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m3, 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust.
Yokota, Satoshi; Hori, Hiroshi; Umezawa, Masakazu; Kubota, Natsuko; Niki, Rikio; Yanagita, Shinya; Takeda, Ken
Aquaporin11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation
Aquaporin-11 (AQP11), a new member of the aquaporin family, is localized in the endoplasmic reticulum (ER). Aqp11\\/ mice neonatally suffer from polycystic kidneys derived from the proximal tubule. Its onset is proceeded by the vacuolization of ER. However, the mechanism for the formation of vacuoles and cysts remains to be clarified. Here, we show that Aqp11\\/ mice and polycystic kidney
Shinji Okada; Takumi Misaka; Yasuko Tanaka; Ichiro Matsumoto; Kenichi Ishibashi; Sei Sasaki; Keiko Abe
Methods for studying habitual behavior in mice.
Habit formation refers to the process by which goal-directed behavior becomes automatized and less sensitive to changes in the value of the goal. It has clear relevance for our understanding of skill learning and addiction. Recent studies have begun to reveal the neural substrates underlying this process. This unit summarizes what is known about the experimental methods used, and provides a protocol for generating and assessing habit formation in mice. PMID:22752897
Rossi, Mark A; Yin, Henry H
Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice.
In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL-C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in HDL size observed by nondenaturing gradient gel electrophoresis. Turnover studies with doubly labeled HDL showed that dietary fat both increase the transport rate (TR) and decreased the fractional catabolic rate of HDL cholesterol ester (CE) and apo A-I, with the largest effect on HDL CE TR. The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway, perhaps as an adaptation to the metabolic load of a high fat diet. The increase in apo A-I TR by dietary fat was confirmed by experiments showing increased apo A-I secretion from primary hepatocytes isolated from animals on the high fat diet. The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation. The dietary fat-induced decrease in HDL CE and apo A-I fractional catabolic rate may have been caused by the increase in HDL particle size, as was suggested by our previous studies in humans. In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet. Images
Hayek, T; Ito, Y; Azrolan, N; Verdery, R B; Aalto-Setala, K; Walsh, A; Breslow, J L
Psychology of Animal Cognition: Piagetian Studies
During the last 15 years, Piaget's theory and methods have been used to investigate the cognitive capacities and development of nonhuman primates as well as of a few avian and mammalian species. Most studies have focused on formal testing of object permanence, but data are also available on sensory-motor intelligence, on the concepts of space and causality, and on imitation.
François Y. Doré; Claude Dumas
Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia.
Hyperhomocysteinemia (HHCY) is a consequence of impaired methionine/cysteine metabolism and is caused by deficiency of vitamins and/or enzymes such as cystathionine beta-synthase (CBS). Although HHCY is an important and independent risk factor for cardiovascular diseases that are commonly associated with hepatic steatosis, the mechanism by which homocysteine promotes the development of fatty liver is poorly understood. CBS-deficient (CBS(-/-)) mice were previously generated by targeted deletion of the Cbs gene and exhibit pathological features similar to HHCY patients, including endothelial dysfunction and hepatic steatosis. Here we show abnormal lipid metabolism in CBS(-/-) mice. Triglyceride and nonesterified fatty acid levels were markedly elevated in CBS(-/-) mouse liver and serum. The activity of thiolase, a key enzyme in beta-oxidation of fatty acids, was significantly impaired in CBS(-/-) mouse liver. Hepatic apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and very low density lipoprotein levels were elevated in CBS(-/-) mice. Serum levels of cholesterol/phospholipid in high density lipoprotein fractions but not of total cholesterol/phospholipid were decreased, and the activity of lecithin-cholesterol acyltransferase was severely impaired in CBS(-/-) mice. Abnormal high density lipoprotein particles with higher mobility in polyacrylamide gel electrophoresis were observed in serum obtained from CBS(-/-) mice. Moreover, serum cholesterol/triglyceride distribution in lipoprotein fractions was altered in CBS(-/-) mice. These results suggest that hepatic steatosis in CBS(-/-) mice is caused by or associated with abnormal lipid metabolism. PMID:15466479
Namekata, Kazuhiko; Enokido, Yasushi; Ishii, Isao; Nagai, Yasuo; Harada, Takayuki; Kimura, Hideo
Juvenile animal toxicity study designs to support pediatric drug development.
The objective of juvenile animal toxicity studies of pharmaceuticals is to obtain safety data, including information on the potential for adverse effects on postnatal growth and development. Studies in juvenile animals may assist in identifying postnatal developmental toxicities or other adverse effects that are not adequately assessed in the routine toxicity evaluations and that cannot be safely or adequately measured in pediatric clinical trials. Unlike the traditional reproductive and developmental toxicology studies that have been discussed in the accompanying reports, the design requirements for toxicity studies in juvenile animals are not explicitly defined in regulatory guidance. However, studies in juvenile animals can be useful in providing safety information necessary to enable pediatric clinical trials in pediatric patients or when there are special concerns for toxicities that cannot be safely or adequately measured in clinical trials. These juvenile animal toxicity studies are designed on a case-by-case basis. General design considerations and examples of study designs for assessment of juvenile animal toxicity are discussed. PMID:20025047
Cappon, Gregg D; Bailey, Graham P; Buschmann, Jochen; Feuston, Maureen H; Fisher, J Edward; Hew, Kok Wah; Hoberman, Alan M; Ooshima, Yojiro; Stump, Donald G; Hurtt, Mark E
Scanning multiple mice in a small-animal PET scanner: Influence on image quality
To achieve high throughput in small-animal positron emission tomography (PET), it may be advantageous to scan more than one animal in the scanner's field of view (FOV) at the same time.However, due to the additional activity and increase of Poisson noise, additional attenuating mass, extra photon scattering, and radial or axial displacement of the animals, a deterioration of image quality
Françoise J. Siepel; Monique G. J. T. B. van Lier; M. L. Chen; Jonathan A. Disselhorst; Antoi P. W. Meeuwis; Wim J. G. Oyen; Otto C. Boerman; Eric P. Visser
Genome-wide association studies in mice.
Genome-wide association studies (GWASs) have transformed the field of human genetics and have led to the discovery of hundreds of genes that are implicated in human disease. The technological advances that drove this revolution are now poised to transform genetic studies in model organisms, including mice. However, the design of GWASs in mouse strains is fundamentally different from the design of human GWASs, creating new challenges and opportunities. This Review gives an overview of the novel study designs for mouse GWASs, which dramatically improve both the statistical power and resolution compared to classical gene-mapping approaches. PMID:23044826
Flint, Jonathan; Eskin, Eleazar
Genome-wide association studies in mice
Genome-wide association studies (GWASs) have transformed the field of human genetics and have led to the discovery of hundreds of genes that are implicated in human disease. The technological advances that drove this revolution are now poised to transform genetic studies in model organisms, including mice. However, the design of GWASs in mouse strains is fundamentally different from the design of human GWASs, creating new challenges and opportunities. This Review gives an overview of the novel study designs for mouse GWASs, which dramatically improve both the statistical power and resolution compared to classical gene-mapping approaches.
Flint, Jonathan; Eskin, Eleazar
Childhood cruelty to animals: a tri-national study.
Childhood cruelty to animals is a symptom of conduct disorder that has been linked to the perpetration of violence in later life. Research has identified several factors associated with its etiology, including social factors. However, no cross-cultural studies on this phenomenon have been reported. This study investigated childhood cruelty to animals in Japan, Australia and Malaysia. Parents of 1,358 children between the ages of 5 and 13 years completed the Children's Attitudes and Behaviours towards Animals questionnaire (CABTA) which assesses Typical and Malicious Cruelty to animals. Analyses revealed no overall differences between children from these countries on either scale. However, younger boys were more likely to be cruel than younger girls in each country, and younger children in Australia and Japan were more likely to be cruel that older children in those countries. The findings are discussed in relation to previous research, and recommendations for future studies are suggested. PMID:19449100
Mellor, David; Yeow, James; Mohd Hapidzal, Noor Fizlee; Yamamoto, Takashi; Yokoyama, Akimitsu; Nobuzane, Yosuke
Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats
Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral
A M Sonabend; I V Ulasov; Y Han; C E Rolle; S Nandi; D Cao; M A Tyler; M S Lesniak; Lesniak
Animal subjectivity: a study into philosophy and theory of animal experience
For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions for further research were proposed: (1) What is the nature of feelings? and (2) Why is it not possible
S. E. E. M. Lijmbach
A Case Study of Memory Loss in Mice
NSDL National Science Digital Library
This discussion case explores the scientific process involved in implementing an animal model in the study of Alzheimer's disease. Students read a short paragraph describing a study in which the brains of "trained" mice were injected with beta-amyloid fragments, which subsequently caused them to forget their tasks. The paragraph is a very short New York Times story reporting on an experimental study originally published in the Proceedings of the National Academy of Sciences. Based on the short description provided, students are asked to identify relevant components of the scientific method (problem, method, results, and conclusions). The case is suitable for a wide variety of science majors and non-majors courses.
Hudecki, Michael S.
Relevance of experimental animal studies to the human experience
Animal experiments are being used to examine a number of physical and biological factors that influence risk estimations though not usually in coordination with epidemiologists. It is clear that the different mechanisms involved in different types of tumors are reflected in the diversity of dose-response relationships. The forms of the dose-response relationships are influenced by both the initial events and their expression. Evidence is accumulating that many initiated cells do not get expressed as overt cancers and host factors may play a major role in the expression of potential tumor cells. There is a need for information about the relationship of the natural incidence and susceptibility to radiation induction for more tumor types. Such experiments will help answer the question of which risk estimate models are appropriate for different tumor types and can be carried out on animals. Perhaps because of the importance of host factors risk estimates as a percentage of the natural incidence appear to be similar for human beings and mice for a small number of tumor types. The elucidation of the mechanisms involved in different tissues while a slow business remains an important role of animal experiments.
Fry, R.J.M.
Animal and human studies with the mitochondria-targeted antioxidant MitoQ.
As mitochondrial oxidative damage contributes to a wide range of human diseases, antioxidants designed to be accumulated by mitochondria in vivo have been developed. The most extensively studied of these mitochondria-targeted antioxidants is MitoQ, which contains the antioxidant quinone moiety covalently attached to a lipophilic triphenylphosphonium cation. MitoQ has now been used in a range of in vivo studies in rats and mice and in two phase II human trials. Here, we review what has been learned from these animal and human studies with MitoQ. PMID:20649545
Smith, Robin A J; Murphy, Michael P
Pancreatic Insulin-Producing Cells Differentiated from Human Embryonic Stem Cells Correct Hyperglycemia in SCID/NOD Mice, an Animal Model of Diabetes
Background Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs), a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs) differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID)/non-obese diabetic (NOD) mice, an animal model of diabetes. Methods We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5–7×106 differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n?=?20). The control group were transplanted with undifferentiated hESCs (n?=?6). Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels. Results The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature ? cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ?8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001). Conclusions The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct hyperglycemia in SCID/NOD mice for ?8 weeks.
Tang, Yu-xiao; Yu, Sheng-qiang; Jin, Shao-hua; Meng, Xiao-mei; Li, Hua-feng; Liu, Fu-jun; Sun, Qiang; Wang, Hai-yan; Li, Jian-yuan
Controlling airborne cues to study small animal navigation
Small animals like nematodes and insects analyze airborne chemical cues to infer the direction of favorable and noxious locations. In these animals, the study of navigational behavior evoked by airborne cues has been limited by the difficulty of precise stimulus control. We present a system that enables us to deliver gaseous stimuli in defined spatial and temporal patterns to freely moving small animals. We use this apparatus, in combination with machine vision algorithms, to assess and quantify navigational decision-making of Drosophila larvae in response to ethyl acetate (a volatile attractant) and carbon dioxide (a gaseous repellant).
Gershow, Marc; Berck, Matthew; Mathew, Dennis; Luo, Linjiao; Kane, Elizabeth A.; Carlson, John R.; Samuel, Aravinthan D.T.
Toxicity of chromated copper arsenate: a study in mice.
Chromated copper arsenate (CCA) was widespread used as a chemical wood preservative with application in the construction of playground equipment, fences, jetties, and naval. Environmental protection agency (EPA) had limited the use of CCA-treated wood on 2002, due to probable implications on both human and environmental health. Although this fact, several industries pursue the use of this product within their manufactories. In addition, the durability of this wood for 60 years, makes these treated products an hazard to the public health. In the present work, studies were explored exposing mice to CCA, during 14, 24, 48, and 96 h for the assessment of acute toxicity of CCA. Kidney and liver were removed, prepared for histology and for metalloid, and copper content evaluation by high resolution inductively coupled plasma mass spectroscopy. The histological results evidenced apparently normal structures for control animals and group exposed to As2O5. On the contrary, the renal sections of the animals treated with CCA revealed epithelium cells desquamation, hyaline, and granular casts in renal tubules lumen. Furthermore, high levels of arsenic were detected in the kidney of animals treated with CCA over 14 and 48 h, being significantly greater than controls. Although this approach underlines the potential hazard of CCA on some vital organs, further testing may be required to establish the impacts on other functions. PMID:20307876
Matos, R C; Vieira, C; Morais, S; Pereira, M L; Pedrosa, J
Abuse potential and physical dependence liability studies with flupirtine maleate in laboratory animals.
Flupirtine maleate is a centrally acting analgesic with a novel chemical structure and pharmacological profile. Because of its central mechanism(s) of action, flupirtine maleate was studied for physical dependence liability and abuse potential using the following four laboratory animal models: (1) mouse jumping test--jumping behaviour after narcotic antagonist challenge; (2) Hosoya test in rats--body weight reduction after drug withdrawal or narcotic antagonist challenge; (3) tolerance in mice--reduced analgesic activity after repeated dosing; and (4) self-administration in addicted Rhesus monkeys. Unlike the narcotic analgesic agents morphine and codeine, flupirtine maleate did not display evidence of physical dependence liability or abuse potential as measured by jumping behaviour in mice or body weight reduction in rats following repeated oral administration. Doses equal to or in excess of its analgesic dose were given for up to five weeks in these studies. No tolerance developed to the analgesic activity of flupirtine maleate in mice or rats dosed for up to 19 consecutive days. Finally, in morphine-dependent Rhesus monkeys, there was no difference in the rate of self-administration of flupirtine maleate when compared to the saline vehicle. Therefore, these results clearly show that flupirtine maleate, in animals, is without abuse potential and physical dependence liability. PMID:3447127
Sofia, R D; Diamantis, W; Gordon, R
NASA Animal Enclosure Module Mouse Odor Containment Study for STS-107 September 15, 1999;SJSU Odor Panel Data
NASA Technical Reports Server (NTRS)
Experiment #153 by Scott Brady is manifested for shuttle flight STS-107. This evaluation of space flight induced stress and its effects on neuronal plasticity will use 18 six month old C57Bl/6 male mice. A 21 day evaluation study was proposed to determine the length of time groups of 6, 9, or 12 mice could be housed in the Animal Enclosure Module (AEM) without odor breakthrough. This study was performed at NASA-Ames Research Center beginning on September 15, 1999. NASA personnel, were responsible for animal care, maintenance, facilities, hardware, etc. San Jose State personnel performed the odor panel evaluations and data reduction. We used similar procedures and methods for earlier tests evaluating female mice.
Holley, Daniel C.; Mele, Gary D.; Poffenroth, Mary; Young, Cliff
John Buckley, Animal Technician
John Buckley is an animal technician who provides murine expertise to the entire Pediatric Oncology Branch. John is well versed in the breeding and husbandry of mice as well as a variety of surgical techniques. John's expertise and teaching serves as a vital resource for the conduct of animal studies in the Immunology Section.
Animal models for the study of adenosine receptor function.
Adenosine receptors represent a family of G-protein coupled receptors that are ubiquitously expressed in a wide variety of tissues. This family contains four receptor subtypes: A1 and A3, which mediate inhibition of adenylyl cyclase; and A2a and A2b, which mediate stimulation of this enzyme. Currently, all receptor subtypes have been genetically deleted in mouse models except for the A2b adenosine receptor, and some have been overexpressed in selective tissues of transgenic mice. Studies involving these transgenic mice indicated that receptor levels are rate limiting, as effects were amplified upon increases in receptor level. The knockout models pointed to clusters of activities related to the physiologies of the cardiovascular and the nervous systems, which are either reduced or enhanced upon specific receptor deletion. Interestingly, the trend of effects on these systems is similar in the A1 and A3 adenosine receptor knockout mice and opposite to the effects observed in the A2a adenosine receptor knockout model. This review summarizes in vitro studies on pathways affected by each adenosine receptor, and primarily focuses on the above in vivo models generated to investigate the physiologic role of adenosine receptors. Furthermore, it illustrates the need for multiple adenosine receptor subtype deficiency studies in mice and the deletion of the A2b subtype. PMID:15389588
Yaar, R; Jones, M R; Chen, J-F; Ravid, Katya
Animal models of chronic tympanic membrane perforation: in response to plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice
Tympanic membrane perforations (TMP) are relatively common but are typically not treated in their acute stage, as most will heal spontaneously in 7–10 days. Those cases which fail to heal within 3 months are called chronic TMP which attract surgical intervention (e.g. myringoplasty), typically with a temporalis fascia autograft. New materials for the repair of chronic TMP are being developed to address deficiencies in the performance of autografts by undergoing evaluation in animal models prior to clinical study. However, there is currently a lack of ideal chronic TMP animal models available, hindering the development of new treatments. Various techniques and animal species have been investigated for the creation of chronic TMP with varied success. In the present commentary, we bring to the attention of readers the recent report by Shen et al. in Journal of Translational Medicine. The study reported the creation of a chronic TMP animal model in plasminogen gene deficient mice. However, the short observation time (9, 19 days), lack of success rate and the scarcity of solid evidence (e.g. otoscopic & histologic images) to confirm the chronicity of TMP warrant a more thorough discussion.
Animal models of chronic tympanic membrane perforation: in response to plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice.
Tympanic membrane perforations (TMP) are relatively common but are typically not treated in their acute stage, as most will heal spontaneously in 7-10 days. Those cases which fail to heal within 3 months are called chronic TMP which attract surgical intervention (e.g. myringoplasty), typically with a temporalis fascia autograft. New materials for the repair of chronic TMP are being developed to address deficiencies in the performance of autografts by undergoing evaluation in animal models prior to clinical study. However, there is currently a lack of ideal chronic TMP animal models available, hindering the development of new treatments. Various techniques and animal species have been investigated for the creation of chronic TMP with varied success. In the present commentary, we bring to the attention of readers the recent report by Shen et al. in Journal of Translational Medicine. The study reported the creation of a chronic TMP animal model in plasminogen gene deficient mice. However, the short observation time (9, 19 days), lack of success rate and the scarcity of solid evidence (e.g. otoscopic & histologic images) to confirm the chronicity of TMP warrant a more thorough discussion. PMID:24669846
Wang, Allen Y; Shen, Yi; Wang, Jeffrey T; Eikelboom, Robert H; Dilley, Rodney J
High-field small animal magnetic resonance oncology studies
NASA Astrophysics Data System (ADS)
This review focuses on the applications of high magnetic field magnetic resonance imaging (MRI) and spectroscopy (MRS) to cancer studies in small animals. High-field MRI can provide information about tumor physiology, the microenvironment, metabolism, vascularity and cellularity. Such studies are invaluable for understanding tumor growth and proliferation, response to treatment and drug development. The MR techniques reviewed here include 1H, 31P, chemical exchange saturation transfer imaging and hyperpolarized 13C MRS as well as diffusion-weighted, blood oxygen level dependent contrast imaging and dynamic contrast-enhanced MRI. These methods have been proven effective in animal studies and are highly relevant to human clinical studies.
Bokacheva, Louisa; Ackerstaff, Ellen; LeKaye, H. Carl; Zakian, Kristen; Koutcher, Jason A.
High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously.
The aim of this study was to assess the capability of small animal PET (SA-PET) devices to image four mice simultaneously to improve the throughput of SA-PET experiments in cancer research. A customized bed was designed to image up to four mice simultaneously. This bed can easily replace the bed provided by the manufacturer and is connected to an anaesthesia device. A mouse-sized phantom was imaged, mimicking simultaneous imaging of four mice with computation of recovery coefficients and spillover ratios (SORs). In addition, eight mice bearing subcutaneous tumours (human embryonal carcinoma, n=22 tumours) were simultaneously imaged in groups of four on an Inveon SA-PET scanner after injection of F-fluoro-D-glucose. Tumour activity (Bq/ml), as determined by the SA-PET, was compared with ex-vivo counting. For a 5-mm rod, recovery coefficients were 1.15 and 1.05 for a phantom imaged at the central field of view or off-centred on the customized bed, respectively. SORair and SORwater were 0.05 and 0.04 for a phantom imaged alone and 0.15 and 0.06 for a phantom imaged with three additional scatter sources, respectively. Correlation between SA-PET and ex-vivo quantification was good (r=0.91, P<0.0001). The mean ratio of PET quantitative data and ex-vivo counting was equal to 0.9 (95% confidence interval: 0.70-1.09). New generation SA-PET may be suitable for simultaneously imaging four tumour-bearing mice, although improvement in scatter correction efficiency appears necessary. The type of customized bed developed in this study could be easily adapted to other large-bore SA-PET scanners. PMID:20683363
Aide, Nicolas; Desmonts, Cédric; Briand, Mélanie; Meryet-Figuiere, Mathieu; Poulain, Laurent
An animal model for the study of Chamomilla in stress and depression: pilot study.
The behavioral and hematological effects of treatment with Chamomilla 6cH in mice subjected to experimental stress are described. Swiss mice were randomly divided into pairs, one animal was inoculated with Ehrlich's tumor, the other was treated daily with Chamomilla 6cH or control or received no treatment. After 7 days, the animals were observed in an open-field arena and blood samples taken. Mice who cohabitated with a sick cage-mate showed a decrease in their general activity, but those treated with Chamomilla 6cH were less severely affected (p=0.0426). No hematological changes were observed. In a second experiment, the forced swimming test was applied to mice pre-treated with Chamomilla 6cH, controls were: water, 10% ethanol or amitriptyline. Only the amitriptyline and ethanol treated groups showed significant excitatory behavior (p=0.0020), Chamomilla 6cH treated animals' scores intermediate between water control and ethanol or amitriptyline. A decrease in the leukocyte count was observed in the amitriptyline and Chamomilla 6cH treated groups (p=0.039). These data suggest that treatment with Chamomilla 6cH is related to the recovery of basal behavioral conditions in mice subjected to stressful conditions. PMID:18657773
Pinto, Sandra Augusta Gordinho; Bohland, Elisabeth; Coelho, Cideli de Paula; Morgulis, Maria Sílvia Furquim de Azevedo; Bonamin, Leoni Villano
Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals
Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore
E´va Pintye
Giant axon formation in mice lacking Kell, XK, or Kell and XK: animal models of McLeod neuroacanthocytosis syndrome.
McLeod neuroacanthocytosis syndrome (MLS) is a rare X-linked multisystem disease caused by XK gene mutations and characterized by hematological and neurological abnormalities. XK, a putative membrane transporter, is expressed ubiquitously and is covalently linked to Kell, an endothelin-3-converting enzyme (ECE-3). Absence of XK results in reduction of Kell at sites where both proteins are coexpressed. To elucidate the functional roles of XK, Kell, and the XK-Kell complex associated with pathogenesis in MLS, we studied the pathology of the spinal cord, anterior roots, sciatic nerve, and skeletal muscle from knockout mouse models, using Kel(-/-), Xk(-/-), Kel(-/-)Xk(-/-), and wild-type mice aged 6 to 18 months. A striking finding was that giant axons were frequently associated with paranodal demyelination. The pathology suggests probable anterograde progression from the spinal cord to the sciatic nerve. The neuropathological abnormalities were found in all three genotypes, but were more marked in the double-knockout Kel(-/-)Xk(-/-) mice than in either Kel(-/-) or Xk(-/-) mice. Skeletal muscles from Xk(-/-) and Kel(-/-)Xk(-/-) mice showed mild abnormalities, but those from Kel(-/-) mice were similar to the wild type. The more marked neuropathological abnormalities in Kel(-/-)Xk(-/-) mice suggest a possible functional association between XK and Kell in nonerythroid tissues. PMID:24405768
Zhu, Xiang; Cho, Eun-Sook; Sha, Quan; Peng, Jianbin; Oksov, Yelena; Kam, Siok Yuen; Ho, Mengfatt; Walker, Ruth H; Lee, Soohee
Development of a small animal peripheral challenge model of Japanese encephalitis virus using interferon deficient AG129 mice and the SA14-14-2 vaccine virus strain.
Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern due to its recent geographic expansion. While commercial vaccines are available and used in some endemic countries, JEV continues to be a public health problem, with 50,000 cases reported annually. Research with virulent JEV in mouse models to develop new methods of prevention and treatment is restricted to BSL-3 containment facilities, confining these studies to investigators with access to these facilities. We have developed an adult small animal peripheral challenge model using interferon-deficient AG129 mice and the JEV live-attenuated vaccine SA14-14-2, thus requiring only BSL-2 containment. A low dose of virus (10PFU/0.1ml) induced 100% morbidity in infected mice. Increased body temperatures measured by implantable temperature transponders correlated with an increase in infectious virus and viral RNA in serum, spleen and brain as well as an increase in pro-inflammatory markers measured by a 58-biomarker multi-analyte profile (MAP) constructed during the course of infection. In the future, the MAP measurements can be used as a baseline for comparison in order to better assess the inhibition of disease progression by other prophylactic and therapeutic agents. The use of the AG129/JEV SA14-14-2 animal model makes vaccine and therapeutic studies feasible for laboratories with limited biocontainment facilities. PMID:24252694
Calvert, Amanda E; Dixon, Kandice L; Delorey, Mark J; Blair, Carol D; Roehrig, John T
Microbiological monitoring of laboratory mice and biocontainment in individually ventilated cages: a field study.
Over recent years, the use of individually ventilated cage (IVC) rack systems in laboratory rodent facilities has increased. Since every cage in an IVC rack may be assumed to be a separate microbiological unit, comprehensive microbiological monitoring of animals kept in IVCs has become a challenging task, which may be addressed by the appropriate use of sentinel mice. Traditionally, these sentinels have been exposed to soiled bedding but more recently, the concept of exposure to exhaust air has been considered. The work reported here was aimed firstly at testing the efficiency of a sentinel-based microbiological monitoring programme under field conditions in a quarantine unit and in a multi-user unit with frequent imports of mouse colonies from various sources. Secondly, it was aimed at determining biocontainment of naturally infected mice kept in an IVC rack, which included breeding of the mice. Sentinels were exposed both to soiled bedding and to exhaust air. The mice which were used in the study carried prevalent infectious agents encountered in research animal facilities including mouse hepatitis virus (MHV), mouse parvovirus (MPV), intestinal flagellates and pinworms. Our data indicate that the sentinel-based health monitoring programme allowed rapid detection of MHV, intestinal flagellates and pinworms investigated by a combination of soiled bedding and exhaust air exposure. MHV was also detected by exposure to exhaust air only. The IVC rack used in this study provided biocontainment when infected mice were kept together with non-infected mice in separate cages in the same IVC rack. PMID:16803642
Brielmeier, M; Mahabir, E; Needham, J R; Lengger, C; Wilhelm, P; Schmidt, J
Study of hepatitis C virus entry in genetically humanized mice.
Approximately 2% of the world's population is chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can culminate in end stage liver disease and liver cancer if the infection is untreated. Current therapy is only partially effective and a vaccine for HCV does not exist. Since the discovery of HCV as the etiologic agent causing hepatitis C several experimental tools have been developed which have improved our understanding of the viral life cycle and the interaction of HCV with human cells. However, it remains challenging to study HCV infection in its native liver environment given its narrow species tropism, limited to humans and chimpanzees. Mice can be rendered susceptible to HCV infection by transplanting human hepatocytes into immunocompromized liver injury strains. Such human liver chimeric mice are useful as a challenge model for human hepatotropic pathogens but their utility is hampered by their inability to mount functional immune responses and practical aspects including high costs, low throughput, and donor-to-donor variability. The barriers that restrict HCV species tropism are incompletely understood. We have previously shown that expression of human CD81 and human OCLN is required for HCV uptake into mouse cells. This led to the construction of a genetically humanized mouse model for HCV infection. Here, we provide a detailed protocol for the generation of these animals and highlight some of its applications for studying HCV biology and preclinical testing of drug and vaccine candidates. PMID:22687621
Dorner, Marcus; Rice, Charles M; Ploss, Alexander
Study of hepatitis C virus entry in genetically humanized mice
Approximately 2% of the world's population is chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can culminate in end stage liver disease and liver cancer if the infection is untreated. Current therapy is only partially effective and a vaccine for HCV does not exist. Since the discovery of HCV as the etiologic agent causing hepatitis C several experimental tools have been developed which have improved our understanding of the viral life cycle and the interaction of HCV with human cells. However, it remains challenging to study HCV infection in its native liver environment given its narrow species tropism, limited to humans and chimpanzees. Mice can be rendered susceptible to HCV infection by transplanting human hepatocytes into immunocompromized liver injury strains. Such human liver chimeric mice are useful as a challenge model for human hepatotropic pathogens but their utility is hampered by their inability to mount functional immune responses and practical aspects including high costs, low throughput, and donor-to-donor variability. The barriers that restrict HCV species tropism are incompletely understood. We have previously shown that expression of human CD81 and human OCLN is required for HCV uptake into mouse cells. This led to the construction of a genetically humanized mouse model for HCV infection. Here, we provide a detailed protocol for the generation of these animals and highlight some of its applications for studying HCV biology and preclinical testing of drug and vaccine candidates.
Dorner, Marcus; Rice, Charles M.; Ploss, Alexander
Studies of allograft immunity in mice
The mechanisms of the in vitro interaction of sensitized lymphocytes and allogeneic target cells has been studied in a tumour allograft system in inbred mice. The cytotoxic effect of sensitized lymphocytes is shown to require the presence of Ca+ + and Mg+ +. Pretreatment of the lymphocytes with trypsin led to inhibition of cytotoxicity, followed by spontaneous reversal after 1–3 hours incubation. Reactivation was found to be blocked by an inhibitor of protein synthesis (cycloheximide). Cortisone was not found to inhibit the lytic interaction significantly; an occasional effect is thought to be due to toxicity of cortisone for lymphocytes as revealed by dye exclusion test. Inhibition of DNA-synthesis with FUdR (an inhibitor of the enzyme thymidine synthetase) did not reduce the lytic activity of sensitized lymphocytes. Isologous anti-target cell sera induced in various strains of inbred mice were found to be ineffective in blocking the cellular immune reaction in vitro when directed against a minor part of the antigenic complex, but strongly inhibitory when reactive against a major part or the whole complex. Similarly, target cells lacking several of the sensitizing H-2 antigens were not lysed. An isologous anti-lymphocytic serum induced in the graft donor strain and directed against the recipient strain (lymphocyte donor) did not inhibit the cytotoxic reaction. In a heterologous system on the other hand, the lytic effect of guinea-pig lymphocytes sensitized against mouse target cells was effectively blocked by an anti-lymphocytic serum induced in mice of the graft donor strain by injection of recipient (guinea-pig) spleen cells.
Mauel, J.; Rudolf, H.; Chapuis, B.; Brunner, K. T.
Transgenic animals as new approaches in pharmacological studies.
Transgenic animals are becoming useful tools for pharmacological studies. The use of transgenic technology raises two types of questions, "How are transgenic animals made?" and "What types of pharmacological questions can be answered using transgenic technologies?" Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromosomes. The second strategy is to select particular genetic loci for site-specific changes. There are two well-established procedures for simple introduction of DNA into an animal genome, pronuclear DNA injection and transduction using a retrovirus. In contrast, methods for targeting specific DNA sequences to definite sites in the chromosomes are evolving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacological studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology. PMID:9131249
Wei, L N
Childhood Cruelty to Animals: A Tri-National Study
ERIC Educational Resources Information Center
Childhood cruelty to animals is a symptom of conduct disorder that has been linked to the perpetration of violence in later life. Research has identified several factors associated with its etiology, including social factors. However, no cross-cultural studies on this phenomenon have been reported. This study investigated childhood cruelty to…
Mellor, David; Yeow, James; Hapidzal, Noor Fizlee Mohd; Yamamoto, Takashi; Yokoyama, Akimitsu; Nobuzane, Yosuke
Student's Ideas About Animals: Results from a National Study
NSDL National Science Digital Library
In the fall of 1999, Science and Children extended an invitation to K-8 teachers to participate in a national study (Barman, Barman, Berglund, and Goldston, 1999). The main focus of this study was to examine students' ideas about animals. This st
Barman, Charles R.; Newhouse, Kay B.; Goldston, M. J.; Cox, Mary L.; Barman, Natalie S.
Interferon ?/? receptor knockout mice as a model to study bluetongue virus infection.
Bluetongue is an arthropod-borne disease caused by a virus of the genus Orbivirus, the bluetongue virus (BTV), which affects ruminant livestock such as cattle, sheep, and goats and wild ruminants such as deer, and camelids. Recently, adult mice with gene knockouts of the interferon ?/? receptor (IFNAR-/-) have been described as a model of lethal BTV infection. IFNAR(-/-) mice are highly susceptible to BTV-1, BTV-4 and BTV-8 infection when the virus is administered intravenously or subcutaneosuly. Disease progression and pathogenesis closely mimics signs of bluetongue disease in ruminants. In the present paper we review the studies where IFNAR(-/-) mice have been used as an animal model to study BTV transmission, pathogenesis, virulence, and protective efficacy of inactivated and new recombinant marker BTV vaccines. Furthermore, we report new data on protective efficacy of different strategies of BTV vaccination and also on induction of interferon ?/? and proinflammatory immune responses in IFNAR(-/-) mice infected with BTV. PMID:24100234
Ortego, Javier; de la Poza, Francisco; Marín-López, Alejandro
An Animal Model of Chronic Aplastic Bone Marrow Failure Following Pesticide Exposure in Mice
The wide use of pesticides for agriculture, domestic and industrial purposes and evaluation of their subsequent effect is of major concern for public health. Human exposure to these contaminants especially bone marrow with its rapidly renewing cell population is one of the most sensitive tissues to these toxic agents represents a risk for the immune system leading to the onset of different pathologies. In this experimental protocol we have developed a mouse model of pesticide(s) induced hypoplastic/aplastic marrow failure to study quantitative changes in the bone marrow hematopoietic stem cell (BMHSC) population through flowcytometric analysis, defects in the stromal microenvironment through short term adherent cell colony (STACC) forming assay and immune functional capacity of the bone marrow derived cells through cell mediated immune (CMI) parameter study. A time course dependent analysis for consecutive 90 days were performed to monitor the associated changes in the marrow's physiology after 30th, 60th and 90th days of chronic pesticide exposure. The peripheral blood showed maximum lowering of the blood cell count after 90 days which actually reflected the bone marrow scenario. Severe depression of BMHSC population, immune profile of the bone marrow derived cells and reduction of adherent cell colonies pointed towards an essentially empty and hypoplastic marrow condition that resembled the disease aplastic anemia. The changes were accompanied by splenomegaly and splenic erythroid hyperplasia. In conclusion, this animal model allowed us a better understanding of clinico-biological findings of the disease aplastic anemia following toxic exposure to the pesticide(s) used for agricultural and industrial purposes.
Chatterjee, Sumanta; Chaklader, Malay; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaudhuri, Samaresh; Law, Sujata
Urea Transporter Physiology Studied in Knockout Mice
In mammals, there are two types of urea transporters; urea transporter (UT)-A and UT-B. The UT-A transporters are mainly expressed in kidney epithelial cells while UT-B demonstrates a broader distribution in kidney, heart, brain, testis, urinary tract, and other tissues. Over the past few years, multiple urea transporter knockout mouse models have been generated enabling us to explore the physiological roles of the different urea transporters. In the kidney, deletion of UT-A1/UT-A3 results in polyuria and a severe urine concentrating defect, indicating that intrarenal recycling of urea plays a crucial role in the overall capacity to concentrate urine. Since UT-B has a wide tissue distribution, multiple phenotypic abnormalities have been found in UT-B null mice, such as defective urine concentration, exacerbated heart blockage with aging, depression-like behavior, and earlier male sexual maturation. This review summarizes the new insights of urea transporter functions in different organs, gleaned from studies of urea transporter knockout mice, and explores some of the potential pharmacological prospects of urea transporters.
Li, Xuechen; Chen, Guangping; Yang, Baoxue
Spontaneous Stereotypy in an Animal Model of Down Syndrome: Ts65Dn Mice
Stereotyped behaviors (e.g., body rocking) occur at high rates in individuals with mental retardation (e.g., Down syndrome). To determine if spontaneous stereotypy occurs in a murine model of Down syndrome, the home cage behavior of Ts65Dn and control mice was monitored during the dark cycle. Motor activity was further assessed in novel automated test chambers, with acoustic startle and rotor
Cortney A. Turner; Michael F. Presti; Howard A. Newman; Paul Bugenhagen; Linda Crnic; Mark H. Lewis
Preflight studies on tolerance of pocket mice to oxygen and heat. III - Effects on eyes
NASA Technical Reports Server (NTRS)
A study was made of the eyes of eight pocket mice exposed to oxygen at partial pressures of 8, 10, or 12 psi over a period of 7 d. At the termination of the exposure, the animals were decompressed to sea-level O2, either immediately or over a period of 30, 60, or 90 min. No pathological changes were found in any of the eyes, except in the retina of one of the animals exposed to 12 psi O2. Here, only a single rod photoreceptor was found damaged, an observation not regarded as significant. Hence, an oxygen partial pressure as high as 12 psi in the canister in which pocket mice were expected to fly on Apollo XVII would probably have no deleterious effect on the eyes of the animals.
Philpott, D. E.; Corbett, R. L.; Black, S.; Takahashi, A.; Leaffer, D.
Pain assessment in animal models: do we need further studies?
In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals.
Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Vigano, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo
Field Research Studying Whales in an Undergraduate Animal Behavior Laboratory
ERIC Educational Resources Information Center
This work describes a new field research laboratory in an undergraduate animal behavior course involving the study of whale behavior, ecology and conservation in partnership with a non-profit research organization--the Blue Ocean Society for Marine Conservation (BOS). The project involves two weeks of training and five weekend trips on whale watch…
MacLaren, R. David; Schulte, Dianna; Kennedy, Jen
Effect of myrrh extract on the liver of normal and bilharzially infected mice. An ultrastructural study.
In the present work, the efficacy of purified oloe-resin extract of myrrh derived from Commiphora molmol tree (commercially known as Mirazid) as a new, natural antischistosomal drug was investigated. The effect of myrrh on the ultrastructural profile of the non infected normal mice liver was also studied. Sixty male mice were used throughout this work and they were divided into 3 main groups (20 animals each): group I, non infected control animals, group II, infected animals and group III, infected animals treated with myrrh extract 8 weeks post infection (500 mg/kg body weight). The drug was given orally on an empty stomach after overnight fasting for five successive days. All animals were sacrificed after 12 weeks from the beginning of the experiment and small pieces of the liver were excised and prepared for ultrastructural study. The liver of the non infected animals which received myrrh extract (group IA) showed a more or less normal ultrastructural profile. Infected groups showed alterations of the ultrastructure of most of the hepatocytes with extensive intercellular fibrosis with abundant granulomas in the portal tract. In the infected treated group, most of the hepatocytes showed normal organelles with numerous microvilli extending into patent spaces of Disse. Marked reduction of granulomas in the portal areas and amelioration of intercellular fibrosis was also observed. On the basis of the observed results, it was concluded that myrrh extract has a promising antischistosomal non hepatotoxic activity. PMID:15125513
Massoud, Ahmed M A; El Ebiary, Faika H; Abd El Salam, Nevert F
Humanimalia: A journal of human/animal interface studies
NSDL National Science Digital Library
The website for the new journal Humanimalia, published by DePauw University, recently released its first issue. The appeal and importance of the journal goes beyond appearance, as the journal states that the study of the human/animal interface has been a "neglected" area of research. In the "Humanimalifesto" link, a lengthy explanation is given, and it notes that one of the main goals of the journal is "to approach animal/human interfaces without relying on stigmatizing critique of philosophical, political, or cultural antagonists." The first issue consists of articles and reviews, including an article called "Hooters for Neuters: Sexist Transgressive Animal Advocacy Campaign?" and a review of the popular Michael Pollan book, "The Omnivore's Dilemma: A Natural History of Four Meals". Visitors interested in submitting an article to the peer-reviewed, interdisciplinary journal should check out the guidelines in the "Call-for-Papers" link on the left side of the page. The "Notes and Bulletins" link, also on the left side of the page, has a notice of an Animal Studies meeting at NYU, and the "Links" area includes information on upcoming conferences.
Sepsis in Old Age: Review of Human and Animal Studies
Sepsis is a serious problem among the geriatric population as its incidence and mortality rates dramatically increase with advanced age. Despite a large number of ongoing clinical and basic research studies, there is currently no effective therapeutic strategy that rescues elderly patients with severe sepsis. Recognition of this problem is relatively low as compared to other age-associated diseases. The disparity between clinical and basic studies is a problem, and this is likely due, in part, to the fact that most laboratory animals used for sepsis research are not old while the majority of sepsis cases occur in the geriatric population. The objective of this article is to review recent epidemiological studies and clinical observations, and compare these with findings from basic laboratory studies which have used aged animals in experimental sepsis.
Starr, Marlene E; Saito, Hiroshi
The development of response surface pathway design to reduce animal numbers in toxicity studies
Background This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. Methods A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. Results The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 ?g/kgBW (95% CI: 383–535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 ?g/kgBW (95% CI: 362–566) and 447 ?g/kgBW (95% CI: 378–504 ?g/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 ?g/kgBW (95% CI: 442–517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Conclusion Optimised RSP design reduces the number of animals needed. The design converges rapidly on the area of interest and is at least as efficient as both the UDPs and RW design.
Tea and Cancer Prevention: Studies in Animals and Humans
ABSTRACT The role of tea in protection,against cancer,has been,supported,by ample,evidence,from studies in cell culture and animal models. However, epidemiological studies have generated inconsistent results, some of which associated tea with reduced risk of cancer, whereas others found that tea lacks protective activity against certain human,cancers. These results raise questions,about,the actual role of tea in human,cancer,that needs,to be addressed.,This article is
Fung-lung Chung; Joel Schwartz; Christopher R. Herzog; Yang-ming Yang
Can results from animal studies be used to estimate dose or low dose effects in humans
We have devised a method to extrapolate biological equilibrium levels between animal species and subsequently to humans. Our initial premise was based on the observation that radionuclide retention is normally a function of metabolism so that direct or indirect measures could be described by a power law based on body weights of test animal species. However, we found that such interspecies comparisons ought to be based on the coefficient of the power equation rather than on the exponential parameter. The method is illustrated using retention data obtained from five non-ruminant species (including humans) that were fed radionuclides with different properties. It appears that biological equilibrium level for radionuclides in man can be estimated using data from mice, rats and dogs. The need to extrapolate low-dose effects data obtained from small animals (usually rodents) to humans is not unique to radiation dosimetry or radiation protection problems. Therefore, researchers have reviewed some quantitative problems connected with estimating low-dose effects from other disciplines, both because of the concern about effects induced by the radionuclide moiety of a radiopharmaceutical and those of the nonradioactive component. The possibility of extrapolating low-dose effects calculated from animal studies to humans is discussed.
Thomas, J.M.; Eberhardt, L.L.
Exploratory study of oral mucosal colonization of human gastric Helicobacter pylori in mice
In this study, human gastric Helicobacter pylori (Hp) was closely attached to the pre-treated mouse buccal mucosa by using artificial oral film to induce the growth and colonization of Hp on the buccal mucosa in mice. Sixty BALB/c mice were divided into three groups, in which Hp biofilm colonization was detected in three mice in Hp film group (Hp mesh biofilm accumulation under an optical microscope; Hp accumulated colonization under an electron microscope). There were no Hp biofilms detected in Hp smear group or the control group with black film. In this study, human gastric Hp was first used to artificially induce the growth and colonization of Hp on the buccal mucosa in mice. The mouse model of oral infection with Hp was initially established, providing animal experimental evidences for oral conditions of growth and colonization of Hp on the buccal mucosa in mice, and providing a workable animal modeling method for further research of joint infection of Hp on the mouth and stomach, as well as the relationship between oral Hp and gastric Hp.
Wan, Xueqin; Tang, Dongsheng; Zhang, Xiaohuan; Li, Hongming; Cui, Zhixin; Hu, Sijuan; Huang, Ming
Neuropeptide Y (NPY) Y 2 receptors mediate behaviour in two animal models of anxiety: evidence from Y 2 receptor knockout mice
The behavioural phenotype of mice lacking neuropeptide Y (NPY) Y2-type receptors was assessed in two well documented animal models of anxiety: namely, the elevated plus maze and the open field. NPY Y2?\\/? mice made more entries into, and spent significantly more time on, the open arms of the elevated plus maze when compared to their wild-type Y2+\\/+ controls (P<0.001). This
John P. Redrobe; Yvan Dumonta; Herbert Herzog
Oncogenicity studies of the cognition-enhancing agent nefiracetam in mice and rats.
Oncogenicity studies of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7), a new cognition-enhancing agent, were carried out in male and female mice and rats. The compound was administered in diet for 104 weeks at dosage levels of 30, 90 and 270 mg/kg/d for mice and of 200, 600 and 1800 ppm for rats. The administration of nefiracetam produced no effects on survival, appearance or behavior. Body weights of the high dose male mice and rats were occasionally significantly decreased when compared to the controls. When calculated on a g/animal/d basis, food consumption was sometimes decreased for these male groups. At necropsy, there was no evidence of treatment related changes, nor were these seen on histopathological examination. All microscopic changes seen in mice and rats were of the usual type commonly occurring in untreated aged B6C3F1 mice and F344 rats. In conclusion, the administration of nefiracetam for 24 months to B6C3F1 mice and F344/DuCrj rats produced only slight effects on body weight in the high dose males with a no-effect level of 90 mg/kg/d for mice or 600 ppm for rats. There was no evidence of an oncogenic effect of nefiracetam. PMID:8018100
Kajimura, T; Satoh, H; Rajasekaran, D; Spicer, E J; Nakashima, N; Takayama, S
NTP Report on the Toxicology Studies of Aspartame (CAS NO. 22839-47-0) in Genetically Modified (FVB Tg.AC Hemizygous) and B6.129-Cdkn2a(tm1Rdp) (n2) Deficient Mice and Carcinogenicity Studies of Aspartame in Genetically Modified (B6.129-trp53(tm1Brd)(n5) Haploinsufficient) Mice (Feed Studies).
National Technical Information Service (NTIS)
The studies described in this report are designed and conducted to characterize and evaluate the toxicologic potential, including carcinogenic activity, of selected chemicals in laboratory animals (usually two species, rats and mice). Chemicals selected f...
Immunotoxicology of arc welding fume: worker and experimental animal studies.
Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses. PMID:22734811
Zeidler-Erdely, Patti C; Erdely, Aaron; Antonini, James M
A novel inhalation challenge set to study animal model of allergic alveolitis.
A novel inhalation challenge set for the study of experimental allergic alveolitis (hypersensitivity pneumonitis) in mice was designed. A finely dispersed aerosol of allergenic extract generated by the commercial ultrasonic nebulizer "TAJFUN MU1" (produced by Medbryt, Warsaw, Poland) was transported to the airtight inhalation chamber. In the chamber were placed 15 perforated containers made of transparent plastic, each containing one mouse. They were coupled in 3 units, each consisted of 5 containers. The constant flow of aerosol through the chamber was assured by commercial vacuum pump "PL 2/3" (AGA LABOR S.C., Warsaw, Poland). The applied set enabled the natural exposure of mice via the inhalation route to known quantities of allergen (usually microbial) suspended in saline, and then dispersed in form of fine aerosol by ultrasonic nebulizer. This method assures the penetration of allergen into the deep parts of lungs, alveoli and bronchioli. The detailed study of histopathological and biochemical changes in the lungs of exposed animals will be the subject of further publications. So far, the retention of endotoxin in the lungs of mice exposed to the extract of a Gram-negative bacterium Pantoea agglomerans and appearance of positive serologic reactions to this extract indicate the effectiveness of the method. PMID:19572490
Golec, Marcin; Skórska, Czes?awa; Lemieszek, Marta; Dutkiewicz, Jacek
Studies on induction of lamotrigine metabolism in transgenic UGT1 mice
A transgenic 'knock-in' mouse model expressing a human UGT1 locus (Tg-UGT1) was recently developed and validated. Although these animals express mouse UGT1A proteins, UGT1A4 is a pseudo-gene in mice. Therefore, Tg-UGT1 mice serve as a 'humanized' UGT1A4 animal model.Lamotrigine (LTG) is primarily metabolized to its N-glucuronide (LTGG) by hUGT1A4. This investigation aimed at examining the impact of pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor (PPAR) activators on LTG glucuronidation in vivo and in vitro. Tg-UGT1 mice were administered the inducers phenobarbital (CAR), pregnenolone-16?-carbonitrile (PXR), WY-14643 (PPAR-?), ciglitazone (PPAR-?), or L-165041 (PPAR-?), once daily for 3 or 4 days. Thereafter, LTG was administered orally and blood samples were collected over 24 h. LTG was measured in blood and formation of LTGG was measured in pooled microsomes made from the livers of treated animals.A three-fold increase in in vivo LTG clearance was seen after phenobarbital administration. In microsomes prepared from phenobarbital-treated Tg-UGT1 animals, 13-fold higher CLint (Vmax/Km) value was observed as compared with the untreated transgenic mice. A trend toward induction of catalytic activity in vitro and in vivo was also observed following pregnenolone-16?-carbonitrile and WY-14643 treatment. This study demonstrates the successful application of Tg-UGT1 mice as a novel tool to study the impact of induction and regulation on metabolism of UGT1A4 substrates.
Argikar, U. A.; Senekeo-Effenberger, K.; Larson, E. E.; Tukey, R. H.; Remmel, R. P.
[Animal experimentation, animal welfare and scientific research].
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. PMID:24660572
Tal, H
Painful dilemmas: A study of the way the public's assessment of animal research balances costs to animals against human benefits.
The conflict between animal costs and human benefits has dominated public as well as academic debates about animal research. However, surveys of public perceptions of animal research rarely focus on this part of attitude formation. This paper traces the prevalence of different attitudes to animal research in the public when people are asked to take benefit and cost considerations into account concurrently. Results from the examination of two representative samples of the Danish public identify three reproducible attitude stances. Approximately 30-35% of people questioned approved of animal research quite strongly, and 15-20% opposed animal research. The remaining 50% were reserved in their views. Further studies will ideally use the measure developed here to make possible relatively fine-grained comparisons and understandings of differences between populations and changes in attitudes over time. PMID:23825251
Lund, Thomas Břker; Mřrkbak, Morten Raun; Lassen, Jesper; Sandře, Peter
Transgenic animal models of neurodegeneration based on human genetic studies
The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease.
Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko
Significance of ecological studies of wild animal reservoirs of zoonoses
The paucity of information on the ecology of wild animal reservoirs over most of the world is one of the factors that has led to hesitation and failure in controlling these diseases in many areas. Extensive application of ecological studies and methods would not only assist in zoonosis control but might well also lead to the discovery of new diseases, to the acquisition of fundamental knowledge capable of application in other fields of biology, and to the finding of new experimental animals for laboratory work. Although such studies properly require the co-operation of a wide variety of specialists—epidemiologists, ecologists, parasitologists, botanists, geologists and climatologists are among those who may to advantage be called upon—in practice much can be accomplished by a few interested and well-equipped field workers backed by a good museum and laboratory services.
Abdussalam, M.
Reproduction in the space environment: Part I. Animal reproductive studies
NASA Technical Reports Server (NTRS)
Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.
Santy, P. A.; Jennings, R. T.; Craigie, D.
Study of interaction of tramadol with amlodipine in mice
Objective: To study a possible interaction between tramadol, an opioid analgesic and amlodipine, a dihydropyridine calcium channel blocker with proposed antinociceptive property. Materials and Methods: Albino mice of Haffkine strain were used for the study. The experiment was carried out using tail-flick method. Different doses of tramadol (50 mg/kg, 22.8 mg/kg and 10 mg/kg) were administered intraperitoneally to select the nonanalgesic dose. The animals were treated with different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg, 3.5 mg/kg) to study its antinociceptive action. Combination of different doses of both the drugs were administered to study antinociceptive effect of the combination. Results: Tramadol, showed dose dependent antinociception which persisted for entire two hours of the study period. Antinociceptive action was seen with amlodipine at a dose of 3.5 mg/kg. Different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg) in combination with the nonanalgesic dose of tramadol (10 mg/kg) produced a significant enhancement of antinociceptive effect of tramadol. Combination of 3.5 mg/kg dose of amlodipine with nonanalgesic dose of tramadol (10 mg/kg) further enhances antinociceptive activity. Conclusion: It is concluded that combination of amlodipine, a N - type calcium channel blocker, with tramadol produce significant enhancement of antinociceptive activity of tramadol.
Modi, Hiral; Mazumdar, Bipa; Bhatt, Jagatkumar
ELF magnetic fields: animal studies, mechanisms of action.
Animal studies can contribute to addressing the issue of possible greater health risk for children exposed to 50-60 Hz extremely low frequency (ELF) magnetic fields (MFs), mostly in terms of teratological effects and cancer. Teratology has been extensively studied in animals exposed to ELF MFs but experiments have not established adverse developmental effects. Childhood leukaemia has been the only cancer consistently reported in epidemiological studies as associated with exposure to ELF MFs. This association has been the basis for the classification as "possibly carcinogenic to humans" by the International Agency for Research on Cancer in 2002. Animal experiments have provided only limited support for these epidemiological findings. However, none but one study used an animal model for acute lymphoblastic leukaemia (ALL), the main form of childhood leukaemia, and exposures to ELF MFs were not carried out over the whole pregnancy period, when the first hit of ALL is assumed to occur. Moreover, there are no generally accepted biophysical mechanisms that could explain carcinogenic effects of low-level MFs. The radical pair mechanism and related cryptochromes (CRY) molecules have recently been identified in birds and other non-mammalian species, as a sensor of the geomagnetic field, involved in navigation. The hypothesis has to be tested in mammalian models. CRY, which is part of the molecular circadian clock machinery, is a ubiquitous protein likely to be involved in cancer cell growth and DNA repair. In summary, we now have some clues to test for a better characterization of the interaction between ALL and ELF MFs exposure. PMID:21914452
Lagroye, Isabelle; Percherancier, Yann; Juutilainen, Jukka; De Gannes, Florence Poulletier; Veyret, Bernard
The pleurodele, an animal model for space biology studies
Pleurodeles waltl, an Urodele amphibian is proposed as a model for space biology studies. Our laboratory is developing three types of experiments in space using this animal: 1.1)in vivo fertilization and development ("FERTILE" project);2.2)influence of microgravity and space radiation on the organization and preservation of spacialized structures in the neurons and muscle cells (in vitro; "CELIMENE" PROJECT);3.3)influence of microgravity on
L. Gualandris; S. Grinfeld; F. Foulquier; P. Kan; A. M Duprat
The Pleurodele, an animal model for space biology studies
NASA Astrophysics Data System (ADS)
Pleurodeles waltl, an Urodele amphibian is proposed as a model for space biology studies. Our laboratory is developing three types of experiments in space using this animal: 1) in vivo fertilization and development (``FERTILE'' project); 2) influence of microgravity and space radiation on the organization and preservation of spacialized structures in the neurons and muscle cells (in vitro; ``CELIMENE'' PROJECT); 3) influence of microgravity on tissue regeneration (muscle, bone, epidermis and spinal cord).
Gualandris, L.; Grinfeld, S.; Foulquier, F.; Kan, P.; Duprat, A. M.
An Animal Model of Type A Cystinuria Due to Spontaneous Mutation in 129S2/SvPasCrl Mice
Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.
Livrozet, Marine; Vandermeersch, Sophie; Mesnard, Laurent; Thioulouse, Elizabeth; Jaubert, Jean; Boffa, Jean-Jacques; Haymann, Jean-Philippe; Baud, Laurent; Bazin, Dominique; Daudon, Michel; Letavernier, Emmanuel
Pathological Aspects of Spontaneous Uveitis and Retinopathy in HLA-A29 Transgenic Mice and in Animal Models of Retinal Autoimmunity: Relevance to Human Pathologies
Purpose: A major increased risk of developing birdshot chorioretinopathy is reported in humans who are HLA-A29-positive. To better characterize this disease, an animal model of HLA-A29-associated disease was developed and the pathology arising spontaneously in these transgenic mice was compared to animal models of autoimmune uveoretinitis and to human pathology. Materials and Methods: HLA-A2902 cDNA (A29c) was obtained from a
Yvonne de Kozak; Serge Camelo; Marika Pla
Hydration with Saline Decreases Toxicity of Mice Injected With Calcitriol in Preclinical Studies
The effectiveness of saline injection in reducing the toxicity profile of calcitriol when coadministered in mice was evaluated. Mortality was used as an end point to study the toxic effects of calcitriol; the relative risk of mortality in mice injected with saline was evaluated from our previously published animal experiments. We discovered that coadministration with 0.25 mL normal saline solution injected intraperitoneally is associated with a lower mortality rate than calcitriol given alone. The estimated relative risk of mortality was 0.0789 (95% confidence interval, 0.0051–1.22; z = 1.82; P = 0.070) when saline is administered with calcitriol compared to calcitriol alone. There was a reduction in serum calcium levels in mice that received saline (11.4 ± 0.15 mg/dL) compared to mice that did not receive saline (12.42 ± 1.61 mg/dL). Hydration with saline seems to reduce mortality and toxicity in mice receiving calcitriol. Given the decrease in mortality rates, intraperitoneal injections of saline should be considered in studies involving mice receiving injections of calcitriol.
Azari, Amir A; Kanavi, Mozhgan R.; Darjatmoko, Soesiawati R.; Lee, Vivian; Kim, KyungMann; Potter, Heather D.; Albert, Daniel M.
Stanford study shows a single antibody shrinks variety of human tumors transplanted into mice
Human tumors transplanted into laboratory mice disappeared or shrank when scientists treated the animals with a single antibody, according to a new study from the Stanford University School of Medicine. The antibody works by masking a protein flag on cancer cells that protects them from macrophages and other cells in the immune system. The scientists achieved the findings with human breast, ovarian, colon, bladder, brain, liver and prostate cancer samples.
Further studies on cyclic erythropoiesis in mice
When young adult female W/Wv mice are given 0.5 micro+Ci /sup 89/Sr/g body weight intravenously, their hematocrit values oscillate from nadirs of 26% to zeniths of 42% with a periodicity of 16 days. The response of the W/Wv mouse to an assortment of radioactive and hematologic stresses have been examined in an effort to understand better the pathophysiology of cyclic erythropoiesis. When the dose of /sup 89/Sr is increased, the amplitude of cycling increases as nadirs are lowered, but periodicity is unchanged. When the dose of /sup 89/Sr is lowered to 0.3 microCi or less, cyclic erythropoiesis of substantial amplitude is observed only after five or six microoscillations. A single hematopoietic insult of 80 rad x-irradiation coupled with phlebotomy produces a transient form of cyclic erythropoiesis, namely, a series of dampened oscillations prior to recovery. Finally, we report that Wv/Wv mice exhibit a form of cyclic erythropoiesis in response to 0.5 microCi /sup 89/Sr/g body weight, in which the hematocrit values of successive nadirs gradually increase, and stabilize at about 100 days. /sup 89/Sr does not induce cyclic erythropoiesis in the +/+, W/+, or W/v/+ mice, the Hertwig strain of anemic mice, or in normal BDF1 mice.
Gibson, C.M.; Gurney, C.W.; Simmons, E.L.; Gaston, E.O.
Studies of human breast cancer metastasis using nude mice
Athymic nude mice have been used in recent years to study the biology of human tumors and to assess therapeutic responses in vivo rather than just in vitro. Some human tumors metastasize in nude mice, providing model systems for analyzing various aspects of the metastatic phenotype of human neoplasms. For breast carcinomas, however, the tumor-take rate of surgical specimens is
Janet E. Price; Ruo Dan Zhang
Using Computational and Mechanical Models to Study Animal Locomotion
Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms' performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: "Integrating living and physical systems."
Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas
Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations
Since a report in 1997 on an increased lymphoma incidence in mice chronically exposed to a mobile phone radiofrequency signal, none of the subsequent long-term studies in rodents have confirmed these results. On the other hand, several of the follow-up co- and carcinogenicity studies are still underway or are presently being initiated. Most of the published long-term studies used 1 exposure level only and suffer from a poor dosimetry which does not consider the animal's growth. Additional points of criticism are a limited, in some cases, questionable histopathology and inadequate group sizes. Overall, if dealing with new chemicals or drugs, these studies would not be acceptable for registration with the responsible authorities. The major critical points are taken into consideration within the European co- and carcinogenicity projects (CEMFEC and PERFORM-A), which are in their final stages and in the US long-term studies in mice and rats which are about to be initiated. Nevertheless, the WHO evaluation for health risk assessment of long-term telephone use and base station exposure will start in late 2005.
Dasenbrock, Clemens [Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Str. 1, 30625 Hannover (Germany)]. E-mail: firstname.lastname@example.com
Electromyographic studies in mdx and wild-type C57 mice.
The electromyographic (EMG) characteristics of human Duchenne muscular dystrophy (DMD) have been well-described. However, to our knowledge, no prior needle electromyographic (EMG) studies of motor unit morphology have been undertaken in muscles from the mdx mouse, an animal that is genetically homologous to DMD. There are significant phenotypic differences between the human and murine dystrophic conditions, bringing into question whether the mdx mouse is an appropriate animal model for DMD. This study was done in order to characterize the EMG findings in mdx mice, compared to normal wild-type mice, and to assess for similarities to DMD. The tibialis anterior and gastrocnemius/soleus muscles from 34 mice (16 C57 wild-type and 18 mdx), divided into four age groups (3, 12, 18, and 24 months), were examined. Wild-type muscles showed normal insertional activity and no abnormal activity at rest. Motor unit action potential (MUAP) parameters were characterized. In contrast to wild-type muscles, mdx muscles showed increased insertional activity, abnormal spontaneous potentials, and the presence of complex repetitive discharges (CRDs). MUAPs showed increased numbers of phases (4.0 +/- 0.6, P < 0.001) and duration (7.1 +/- 1.2 ms, P < 0.02), as well as late components (15%). These EMG data indicate that mdx muscles display EMG characteristics similar to those found in muscles from boys with DMD, lending credence to the mdx mouse as an animal model for this disease. The data obtained in this study indicate a potential role for EMG as an in vivo, objective measurement tool that could be used longitudinally to monitor the effects of therapeutic interventions in mdx mice. This is important as there are few objective measures of muscle function in murine models that do not require killing the animal. PMID:16281275
Han, Jay J; Carter, Gregory T; Ra, Jennifer J; Abresch, R Ted; Chamberlain, Jeffrey S; Robinson, Lawrence R
Electron microscopic radioautographic study on protein synthesis in hepatocyte mitochondria of aging mice.
For the purpose of studying the aging changes of intramitochondrial protein synthesis in mouse hepatocytes, 10 groups of aging mice, each consisting of 3 individuals (total 30), from fetal day 19 to postnatal month 24, were injected during development with 3H-leucine, a protein precursor, sacrificed 1 h later, and the liver tissues processed for electron microscopic (EM) radioautography. On EM radioautograms obtained from each animal, the number of mitochondria, the number of labeled mitochondria, and the mitochondrial labeling index labeled with silver grains due to 3H-leucine showing protein synthesis in each mononucleate hepatocytes were counted and the averages in respective aging groups were compared. From the results, it was demonstrated that the numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein syntheses in mononucleate hepatocytes of mice at various ages from embryonic day 19 to postnatal month 24 increased and decreased due to development and aging of animals. PMID:17173177
Nagata, Tetsuji
Advancing Animal Models of Human Type 1 Diabetes by Engraftment of Functional Human Tissues in Immunodeficient Mice
Despite decades of studying rodent models of type 1 diabetes (T1D), no therapy capable of preventing or curing T1D has successfully been translated from rodents to humans. This inability to translate otherwise promising therapies to clinical settings likely resides, to a major degree, from significant species-specific differences between rodent and human immune systems as well as species-related variances in islets in terms of their cellular composition, function, and gene expression. Indeed, taken collectively, these differences underscore the need to define interactions between the human immune system with human ? cells. Immunodeficient mice engrafted with human immune systems and human ? cells represent an interesting and promising opportunity to study these components in vivo. To meet this need, years of effort have been extended to develop mice depleted of undesirable components while at the same time, allowing the introduction of constituents necessary to recapitulate physiological settings as near as possible to human T1D. With this, these so-called "humanized mice" are currently being used as a preclinical bridge to facilitate identification and translation of novel discoveries to clinical settings.
Brehm, Michael A.; Powers, Alvin C.; Shultz, Leonard D.; Greiner, Dale L.
Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons and causes progressive muscle weakness and atrophy. The etiology and pathogenesis of ALS are largely unknown and no effective treatment is presently available. About 10% of patients have the familial or inherited form of the disease (fALS), among which 20% is linked to mutations with Cu2+/Zn2+ superoxide dismutase (mSOD1). Transgenic animals expressing human mSOD1 are excellent models for understanding not only fALS but sporadic ALS as well. Pathological features in both ALS patients and mSOD1 transgenic animals' spinal cords share commonalties including the accumulation of misfolded protein inclusions. Recent proteomic investigations on ALS animal models have discovered alterations in protein expression, protein-protein interactions and post-translational modifications. These efforts have revealed aspects of potential pathogenic mechanisms and identified probable therapeutic targets. The present review summarizes the major findings of proteomics studies performed on the mSOD1 mice with particular emphasis on the spinal cord proteome. These results are compared with those reported using cell cultures or specimens obtained from ALS patients. The convergence of pathogenic processes on protein chaperone function, and its relationship to protein degradation, metabolic dysfunction and oxidative signaling events is discussed.
Jain, Mohit Raja; Ge, Wei-wen; Elkabes, Stella; Li, Hong
Chimeric Mice with Humanized Liver: Tools for the Study of Drug Metabolism, Excretion, and Toxicity
Recent developments in animal models have allowed the creation of mice with genetic alterations that cause hepatocyte damage that results, over time, in the loss of native hepatocytes. If donor, human hepatocytes are transplanted into these animals, they repopulate the host liver, frequently replacing over 70% of the native liver with human cells. Immunodeficient mice that overexpress urokinase-type plasminogen activator (uPA) and, alternatively, with a knockout of the fumarylacetoacetate hydrolase (Fah) genes are the two most common mouse models for these studies. These mice are called chimeric or "humanized" because the liver is now partially repopulated with human cells. In this report we will review the published work with respect to Phase I and Phase II metabolic pathways and the expression of hepatic transport proteins. While the studies are still at the descriptive stage, it is already clear that some humanized mice display high levels of repopulation with human hepatocytes, express basal and inducible human CYP450 genes, and human conjugation and hepatic transport pathways. When the strengths and weaknesses of these humanized mouse models are fully understood, they will likely be quite valuable for investigations of human liver-mediated metabolism and excretion of drugs and xenobiotics, drug–drug interactions, and for short- and long-term investigation of the toxicity of drugs or chemicals with significant human exposure.
Strom, Stephen C.; Davila, Julio; Grompe, Markus
Adriamycin Cardiotoxicity: A Feasibility Study in Mice.
National Technical Information Service (NTIS)
Adriamycin (NSC No. 123127) was injected IV into mice of both sexes of BDF1, CDF and Swiss CD strains to determine if the mouse was a feasible model for anthracycline cardiotoxicity. Following range finding and LD50 determinations, 4 dosage levels (per se...
J. A. Will G. A. Splitter A. Rademakers L. Regel S. R. de Dennis
20 years studying p53 functions in genetically engineered mice
Cell and molecular biological studies of p53 functions over the past 30 years have been complemented in the past 20 years by studies that use genetically engineered mice. As expected, mice that have mutant Trp53 alleles usually develop cancers of various types more rapidly than their counterparts that have wild-type Trp53 genes. These mouse studies have been instrumental in providing
Lawrence A. Donehower; Guillermina Lozano
Advances in genome studies in plants and animals.
The area of plant and animal genomics covers the entire suite of issues in biology because it aims to determine the structure and function of genetic material. Although specific issues define research advances at an organism level, it is evident that many of the fundamental features of genome structure and the translation of encoded information to function share common ground. The Plant and Animal Genome (PAG) conference held in San Diego (California), in January each year provides an overview across all organisms at the genome level, and often it is evident that investments in the human area provide leadership, applications, and discoveries for researchers studying other organisms. This mini-review utilizes the plenary lectures as a basis for summarizing the trends in the genome-level studies of organisms, and the lectures include presentations by Ewan Birney (EBI, UK), Eric Green (NIH, USA), John Butler (NIST, USA), Elaine Mardis (Washington, USA), Caroline Dean (John Innes Centre, UK), Trudy Mackay (NC State University, USA), Sue Wessler (UC Riverside, USA), and Patrick Wincker (Genoscope, France). The work reviewed is based on published papers. Where unpublished information is cited, permission to include the information in this manuscript was obtained from the presenters. PMID:24626952
Appels, R; Nystrom-Persson, J; Keeble-Gagnere, G
A Gamma Ray Imaging Device for Small-Animal Studies
NASA Astrophysics Data System (ADS)
A novel, modular nuclear imaging device for in vivo imaging of small animals is described. A segmented scintillator is coupled to a position-sensitive photomultiplier. This combination is used to view the living system under study with a variety of collimators employed to limit the angular acceptance. A personal computer is coupled to a CAMAC electronic system for event-by-event data acquisition and subsequent selective data analysis. The system has been designed to exploit the availability of a wide range of ligands tagged with the isotope 125I. It has most recently been employed for a study of the transport of the cocaine analog, RTI-55, to the brain of a mouse. Results of studies to date and options for future expansion of the system will be described.
Saunders, Robert; Bradley, Eric; Majewski, Stan; Saha, Margaret S.; Weisenberger, Andrew G.; Welsh, Robert E.
Radioprotectors and Tumors: Molecular Studies in Mice
This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation
Gayle Woloschak, David Grdina
Towards ethically improved animal experimentation in the study of animal reproduction.
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. PMID:18638100
Blache, D; Martin, G B; Maloney, S K
Studies on Sarcocystis species II. Infection in wild and feral animals — prevalence and transmission
Wild and feral animals in New Zealand were examined by a muscle-digest technique, and histology. Sarcocystis spp. were found in red deer, feral goats, feral pigs, rats, mice, and rabbits, and the prevalence of infection recorded. No Sarcocystis spp. were found in 8 wallabies and 62 possums. Sarcocystis spp. in rats and rabbits were transmitted to cats, and a species
G. H. Collins; W. A. G. Charleston
Development of an Animal Holding Facility for Space Shuttle studies
NASA Technical Reports Server (NTRS)
The modular Research Animal Holding Facility (RAHF) developed by NASA is described. Besides providing general housing for various animal species, the RAHF is designed to minimize disturbance of the specimens caused by vehicle and mission operations. The RAHF system offers life-sustaining capabilities, such as food, water, and waste removal, as well as environmental control. Modularity of construction to accommodate a variety of small animals and associated instrumentation ensures continued use of RAHF as the sophistication of experiments increases on subsequent missions.
Berry, W. E.; Bowman, G. H.; Jagow, R. B.; Olcott, T. M.
Social Learning in Animals: Empirical Studies and Theoretical Models
NSDL National Science Digital Library
This peer-reviewed article from BioScience is about social learning in animals. The last two decades have seen a virtual explosion in empirical research on the role of social interactions in the development of animals' behavioral repertoires, and a similar increase in attention to formal models of social learning. Here we first review recent empirical evidence of social influences on food choice, tool use, patterns of movement, predator avoidance, mate choice, and courtship, and then consider formal models of when animals choose to copy behavior, and which other animals' behavior they copy, together with empirical tests of predictions from those models.
BENNETT G. GALEF JR. and KEVIN N. LALAND (;)
Proteomic study on gender differences in aging kidney of mice
BACKGROUND: This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry
Hanna Amelina; Susana Cristobal
Toxicological studies for some agricultural waste extracts on mosquito larvae and experimental animals
Objective To evaluate some agricultural waste extracts as insecticide and their effects on enzyme activities in liver and kidney of male mice. Methods The insecticidal activity of five tested compounds (one crude extract and 4 waste compounds) was bioassay against the 3rd instars of the Culex pipiens (Cx. pipiens) larvae in the laboratory. The LC50 values of eucalyptol, apricot kernel, Rice bran, corn, black liquor and white liquor are 91.45, 1 166.1, 1 203.3, 21 449.65, 4 025.78 and 6 343.18 ppm, respectively. Selection of the compounds for the subsequent studies was not only dependent on LC50 values but also on the persistence of these wastes products on large scale. Results White and black liquor did not produce any gross effect at 200 mg/Kg body weight. No apparent toxic symptoms were observed in tested animals during the whole period of the experiment which run out for 14 days. No statistically significance was observed in the enzyme cholinesterase activity, the activities of liver enzymes and kidney function in treated mice with black and white liquors. While, no and slight inhibition was observed after the 2 weeks of treatment period with deltamethrin and fenitrothion reached to about 24% in plasma cholinesterase enzyme activity. Significantly increase in the activities of liver enzymes and kidney function in treated mice with deltamethrin and fenitrothion. Conclusions Black liquor can be used efficiently to control Cx. pipiens larvae under laboratory condition. Environmental problem caused by rice straw can be solved by converting the waste material to beneficial natural selective insecticide.
El-Maghraby, Somia; Nawwar, Galal A; Bakr, Reda FA; Helmy, Nadia; Kamel, Omnia MHM
The use of on-animal acoustical recording devices for studying animal behavior.
Audio recordings made from free-ranging animals can be used to investigate aspects of physiology, behavior, and ecology through acoustic signal processing. On-animal acoustical monitoring applications allow continuous remote data collection, and can serve to address questions across temporal and spatial scales. We report on the design of an inexpensive collar-mounted recording device and present data on the activity budget of wild mule deer (Odocoileus hemionus) derived from these devices applied for a 2-week period. Over 3300 h of acoustical recordings were collected from 10 deer on their winter range in a natural gas extraction field in northwestern Colorado. Analysis of a subset of the data indicated deer spent approximately 33.5% of their time browsing, 20.8% of their time processing food through mastication, and nearly 38.3% of their time digesting through rumination, with marked differences in diel patterning of these activities. Systematic auditory vigilance was a salient activity when masticating, and these data offer options for quantifying wildlife responses to varying listening conditions and predation risk. These results (validated using direct observation) demonstrate that acoustical monitoring is a viable and accurate method for characterizing individual time budgets and behaviors of ungulates, and may provide new insight into the ways external forces affect wildlife behavior. PMID:23919149
Lynch, Emma; Angeloni, Lisa; Fristrup, Kurt; Joyce, Damon; Wittemyer, George
Current Animal Models: Cotton Rat Animal Model
The cotton rat ( Sigmodon hispidus ) model has proven to be a suitable small animal model for measles virus pathogenesis to fill the niche between tissue culture\\u000a and studies in macaques. Similar to mice, inbred cotton rats are available in a microbiologically defined quality with an\\u000a ever-increasing arsenal of reagents and methods available for the study of infectious diseases.
S. Niewiesk
Telemetry in Biometeorological Studies, Telemetry in Animal Biometeorology.
National Technical Information Service (NTIS)
The paper reviews the remarkable changes in the last 40-50 years in the way measurements are made in animal biometeorology. The experiments which were done to describe the adaptations which made the life of the animal possible, were accomplished with meas...
G. E. Folk J. R. Copping
Various cages are frequently used in assessing the effects of pesticides on non-target animals. In some cases, small animals offer advantages over larger ones because they may be more economical to raise in the laboratory or to purchase; immature stages often are more sensitive t...
Animal Rights: Selected Resources and Suggestions for Further Study.
ERIC Educational Resources Information Center
Presents an annotated list of selected resources intended to serve as a guide to the growing amount of material on animal rights. Suggestions to aid in additional research include subject headings used to find books, indexes used to locate periodical articles, sources for locating organizations, and a selected list of animal rights organizations.…
Davidoff, Donald J.
Animal welfare and use of silkworm as a model animal.
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. PMID:23006994
Sekimizu, N; Paudel, A; Hamamoto, H
Structure and mechanical properties of Ank/Ank mutant mouse dental tissues--an animal model for studying periodontal regeneration.
Enamel, dentine and cementum are dental tissues with distinct functional properties associated with their unique hierarchical structures. Some potential ways to repair or regenerate lost tooth structures have been revealed in our studies focused on examining teeth obtained from mice with mutations at the mouse progressive ankylosis (ank) locus. Previous studies have shown that mice with such mutations have decreased levels of extracellular inorganic pyrophosphate (PP(i)) at local sites resulting in ectopic calcification in joint areas and in formation of a significantly thicker cementum layer when compared with age-matched wild-type (WT) tissue [Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000;289:265-70; Nociti Jr FH, Berry JE, Foster BL, Gurley KA, Kingsley DM, Takata T, et al. Cementum: a phosphate-sensitive tissue. J Dent Res 2002;81:817-21]. As a next step, to determine the quality of the cementum tissue formed in mice with a mutation in the ank gene (ank/ank), we compared the microstructure and mechanical properties of cementum and other dental tissues in mature ank/ank vs. age-matched WT mice. Backscattered scanning electron microscopy (SEM) imaging and transmission electron microscopy (TEM) analyses on mineralized tissues revealed no decrease in the extent of mineralization between ank/ank cementum vs. WT controls. Atomic-force-microscopy-based nanoindentation performed on enamel, dentine or cementum of ank/ank vs. age-matched WT molars revealed no significant difference in any of the tested tissues in terms of hardness and elastic modulus. These results indicate that the tissue quality was not compromised in ank/ank mice despite faster rate of formation and more abundant cementum when compared with age-matched WT mice. In conclusion, these data suggest that this animal model can be utilized for studies focused on defining mechanisms to promote cementum formation without loss of mechanical integrity. PMID:19338977
Fong, H; Foster, B L; Sarikaya, M; Somerman, M J
USC study finds fasting weakens cancer in mice
Cancer in animals appears less resilient and chemotherapy drugs work better when combined with cycles of short, severe fasting, shows a University of Southern California study. Even fasting on its own effectively treated a majority of cancers tested in animals, including cancers from human cells.
A non-destructive technique for 3-D microstructural phenotypic characterisation of bones in genetically altered mice: preliminary data in growth hormone transgenic animals and normal controls
A non-destructive, three-dimensional technique for microstructural phenotypic characterisation of skeletal elements in genetically altered mice is presented. Preliminary data in bovine growth-hormone transgenic animals and control littermates are shown. The technique is based on microcomputed tomography (7CT) and digital postprocessing and allows for a differential quantitative analysis of the cortical and trabecular bone compartments in the axial and peripheral skeleton.
Heiko Graichen; Eva-Maria Lochmüller; Eckhard Wolf; Bernd Langkabel; Tobias Stammberger; Michael Haubner; Ingrid Renner-Müller; Karl-Hans Englmeier; F. Eckstein
Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone disease
The aims were to optimize reproducibility and establish [18F]fluoride ion bone scanning in mice, using a dedicated small animal positron emission tomography (PET) scanner (microPET) and to correlate functional findings with anatomical imaging using computed tomography (microCAT). Optimal tracer uptake time for [18F]fluoride ion was determined by performing dynamic microPET scans. Quantitative reproducibility was measured using region of interest (ROI)-based
Frank Berger; Yu-Po Lee; Andreas M. Loening; Arion Chatziioannou; Stephen J. Freedland; Richard Leahy; Jay R. Lieberman; Arie S. Belldegrun; Charles L. Sawyers; Sanjiv S. Gambhir
Nonclinical toxicology studies with zidovudine: genetic toxicity tests and carcinogenicity bioassays in mice and rats.
Zidovudine (ZDV), an antiviral drug active in the treatment of acquired immunodeficiency syndrome (recommended human dose, 100 mg every 4 hr while awake), was evaluated for mutagenic and carcinogenic potential in a battery of short-term in vitro and in vivo assays and in lifetime studies in mice and rats. In L5178Y mouse lymphoma cells (tk+/- locus), a weak positive result was obtained only at the highest concentrations tested (4000 to 5000 micrograms/ml) in the absence of metabolic activation. In the presence of metabolic activation, the drug was weakly mutagenic at concentrations of 1000 micrograms/ml and higher. Following 24 hr treatment in the absence of metabolic activation, ZDV was moderately mutagenic at concentrations up to 600 micrograms/ml; dose-related structural chromosomal alterations were seen at concentrations of 3 micrograms/ml and higher in cultured human lymphocytes. Such effects were not noted at the two lowest concentrations tested, 0.3 and 1 microgram/ml, and BALB/c-3T3 cells were transformed at concentrations of 0.5 microgram/ml and higher. No effects were seen in the Ames Salmonella plate incorporation and preincubation modification assays (possibly due to bacteriocidal activity of ZDV at low concentrations) at concentrations ranging from 0.01 to 10 micrograms/plate or in a single-dose intravenous bone marrow cytogenetic assay in CD rats. In multidose micronucleus studies, increases in micronucleated erythrocytes were seen in mice at doses of 100 to 1000 mg/kg/day. Similar results were seen in rats and mice after 4 or 7 days of dosing at 500 mg/kg/day. In carcinogenicity bioassays, adjusted doses of 20, 30, or 40 mg/kg/day and 80, 220, and 300 mg/kg/day were given to CD-1 mice and CD rats, respectively, for up to 22 months in mice and 24 months in rats. ZDV caused a macrocytic, normochromic anemia in both species. No evidence of carcinogenicity was seen in male mice or rats. In female mice, five malignant and two benign vaginal epithelial neoplasms occurred in animals given 40 mg/kg/day. A single benign vaginal epithelial tumor was seen in a mouse given 30 mg/kg/day. In rats, two malignant vaginal epithelial neoplasms were seen in animals given 300 mg/kg/day. In a 7-day study in mice, ZDV was shown to be devoid of estrogenic activity. In an oral pharmacokinetics study, the AUC was 17 and 140 micrograms/ml.hr in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. In contrast, the average steady-state concentration in humans at the recommended daily dose is 0.62 microgram/ml. Twenty-four hour urine concentrations were 1245 and 4417 micrograms/ml in female mice and rats given 40 or 300 mg/kg of ZDV, respectively. These values were approximately 26- and 136-fold higher than the human urine concentration at the recommended daily dose. In a one- to three-day study with intravenously administered sodium fluoroscein in rats and mice, retrograde flow of urine into the vagina was demonstrated. In a subsequent lifetime carcinogenicity bioassay in mice in which ZDV was given intravaginally at concentrations of 5 or 20 mg ZDV/ml in saline, 13 vaginal squamous cell carcinomas were seen at the highest concentration tested. It was concluded that the vaginal tumors seen in the oral carcinogenicity studies were the result of chronic local exposure of the vaginal epithelium to high urine concentrations of ZDV. PMID:8921318
Ayers, K M; Clive, D; Tucker, W E; Hajian, G; de Miranda, P
Sponge implant in Swiss mice as a model for studying loxoscelism.
Envenomation by Loxosceles spider bite leads to a set of signs and symptoms, called loxoscelism, which in most cases manifests through the dermonecrotic frame. The development of a smaller size animal model, of easy handling and maintenance, and lower cost is needed to study the loxoscelism pathogenesis. The inflammatory effects of the Loxosceles similis crude venom was evaluated considering neutrophil and macrophage activation, vasodilatation, hyperhaemia, edema and hemorrhage and TNF-? and VEGF production using the murine sponge implant model. Thirty two male Swiss mice (6-8 weeks old) were implanted subcutaneously with polyether-polyurethane sponge discs. Fourteen days post implantation, animals were separated into two groups: (1) control group--16 mice received 30 ?L of saline intra-implant; (2) treated group-sixteen mice injected with 0.5 ?g/30 ?L of L. similis crude venom intra-implant. The animals were euthanized with xylazine/ketamine after 1 and 4 h post- injection. Microscopically, implants of the treated groups presented an acute inflammation characterized by: neutrophilic infiltrate, edema, vasodilatation hyperhaemia, and severe hemorrhage. Some vessels presented ruptured walls. Under morphometric analysis, vessel area was bigger in the treated groups compared with the control ones. The biochemical parameters, hemoglobin content, inflammatory enzyme activities (myeloperoxidase and n-acethyl-?-D glucosaminidase) and levels of the cytokines, TNF-? and VEGF, were also significantly higher in the venom-treated groups. The effects of Loxosceles venom in the granulation tissue of the implant in mice were similar to those observed in cutaneous loxoscelism in other species (human and rabbits). Consequently, the murine sponge implant model provides a new method to investigate cellular/molecular mechanisms associated with cutaneous loxoscelism. PMID:22406472
Pereira, Núbia Braga; Campos, Paula Peixoto; de Jesus Oviedo Socarrás, Teresa; Pimenta, Thaiane Salgado; Parreiras, Patrícia Martins; Silva, Soraia Silvéria; Kalapothakis, Evanguedes; Andrade, Silvia Passos; Moro, Luciana
Developmental effects of SSRIs: lessons learned from animal studies.
Selective serotonin reuptake inhibitors (SSRIs) are utilized in the treatment of depression in pregnant and lactating women. SSRIs may be passed to the fetus through the placenta and the neonate through breastfeeding, potentially exposing them to SSRIs during peri- and postnatal development. However, the long-term effects of this SSRI exposure are still largely unknown. The simplicity and genetic amenability of model organisms provides a critical experimental advantage compared to studies with humans. This review will assess the current research done in animals that sheds light on the role of serotonin during development and the possible effects of SSRIs. Experimental studies in rodents show that administration of SSRIs during a key developmental window creates changes in brain circuitry and maladaptive behaviors that persist into adulthood. Similar changes result from the inhibition of the serotonin transporter or monoamine oxidase, implicating these two regulators of serotonin signaling in developmental changes. Understanding the role of serotonin in brain development is critical to identifying the possible effects of SSRI exposure. PMID:17706396
Borue, Xenia; Chen, John; Condron, Barry G
Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study
The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.
Lee, Don Haeng [Inha University, College of Medicine, Department of Internal Medicine (Korea, Republic of); Kang, Sung-Gwon [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of)], E-mail: firstname.lastname@example.com; Jeong, Seok [Inha University, College of Medicine, Department of Internal Medicine (Korea, Republic of); Yoon, Chang Jin; Choi, Jung-Ah [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of); Byun, Ju Nam [Chosun University, College of Medicine, Department of Radiology (Korea, Republic of); Park, Jae Hyung [Seoul National University Bundang Hospital, Department of Diagnostic Radiology (Korea, Republic of); Lee, Kyu Back [Korea University, College of Medicine, Department of Biomedical Engineering (Korea, Republic of)
Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.
Transgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping. PMID:20615433
Codita, Alina; Gumucio, Astrid; Lannfelt, Lars; Gellerfors, Pär; Winblad, Bengt; Mohammed, Abdul H; Nilsson, Lars N G
Studies on the protective effects of Boerhaavia diffusa L. against gamma radiation induced damage in mice.
The radioprotective effect of the hydro-alcoholic extract of Boerhaavia diffusa was studied using the in vivo mice model. The sublethally irradiated mice (600 rads, single dose) were treated intraperitoneally with 20 mg/kg of the extract. The animals were sacrificed at different time periods after the whole-body radiation. The most affected tissues--bone marrow and intestine--were considerably protected by the intraperitoneal administration of B. diffusa as estimated by bone marrow cellularity, maturing monocytes, and intestinal glutathione. Total white blood cell count was lowered drastically after radiation exposure (ninth day, 1500+/-500 cells/ mm(3)). When the animals were exposed to radiation and treated with B. diffusa, the total white blood cell count was lowered only to 4000+/-400 cells/mm(3) on the third day, and it reached an almost normal level (6250+/-470 cells/mm(3)) by the ninth day. The elevated level of serum and liver alkaline phosphatase after radiation exposure was reduced in the B. diffusa-treated group. The serum and liver glutamate pyruvate transferase, which were elevated after radiation exposure, were also reduced by treatment with B. diffusa compared to the control. The lipid peroxidation level also increased in the irradiated animals both in the liver and serum, but in B. diffusa-treated animals, there was a significant reduction in lipid peroxidation levels. The agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to gamma radiation showed heavy damage that was reduced by treatment with B. diffusa. These results are indicative of the radioprotective effect of the whole-plant extract of B. diffusa. PMID:18048886
Manu, K A; Leyon, P V; Kuttan, Girija
Rodents for comparative aging studies: from mice to beavers.
After humans, mice are the best-studied mammalian species in terms of their biology and genetics. Gerontological research has used mice and rats extensively to generate short- and long-lived mutants, study caloric restriction and more. Mice and rats are valuable model organisms thanks to their small size, short lifespans and fast reproduction. However, when the goal is to further extend the already long human lifespan, studying fast aging species may not provide all the answers. Remarkably, in addition to the fast-aging species, the order Rodentia contains multiple long-lived species with lifespans exceeding 20 years (naked mole-rat, beavers, porcupines, and some squirrels). This diversity opens great opportunities for comparative aging studies. Here we discuss the evolution of lifespan in rodents, review the biology of slow-aging rodents, and show an example of how the use of a comparative approach revealed that telomerase activity coevolved with body mass in rodents. PMID:19424861
Gorbunova, Vera; Bozzella, Michael J; Seluanov, Andrei
Effects of Developmental Bisphenol A Exposure on Reproductive-Related Behaviors in California Mice (Peromyscus californicus): A Monogamous Animal Model
Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist- antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a "pure" estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies.
Williams, Scott A.; Jasarevic, Eldin; Vandas, Gregory M.; Warzak, Denise A.; Geary, David C.; Ellersieck, Mark R.; Roberts, R. Michael; Rosenfeld, Cheryl S.
Oral Toxicity of Okadaic Acid in Mice: Study of Lethality, Organ Damage, Distribution and Effects on Detoxifying Gene Expression
In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals.
Vieira, Andres C.; Rubiolo, Juan A.; Lopez-Alonso, Henar; Cifuentes, Jose Manuel; Alfonso, Amparo; Bermudez, Roberto; Otero, Paz; Vieytes, Mercedes R.; Vega, Felix V.; Botana, Luis M.
Experimental CO2 laser myringotomy: a preliminary animal study
NASA Astrophysics Data System (ADS)
Myringotomy--a procedure in which a perforation is made in the tympanic membrane (TM) is performed to gain access to the middle ear for diagnostic or therapeutic reasons. Some medical conditions, especially middle ear infections require an opening that remains patent for weeks or even months. A conventional myringotomy usually closes in a few days which is insufficient time for an underlying disease to resolve. There have been studies reporting modest closure delays of myringotomies done by CO2 laser from the beginning of 1980's and the procedure has not gained popularity in clinical practice. Many of the mechanisms affecting TM healing delays remain unknown. In an animal model we investigated the closure rates of TM perforations after different types of myringotomies. The animals formed three experimental groups: (1) both ears had a semicircular myringotomy produced either with a knife or with a CO2 laser; (2) both ears had a round laser myringotomy (1.2 mm in diameter) produced either in a single shot or by a series of small overlapping shots; (3) both ears had laser myringotomy either kidney shaped (1.2 X 2 mm) or round (1.2 mm in diameter) produced by a series of small shots. All myringotomies closed within 42 days without complications. The mean patency of knife myringotomies was significantly shorter (9.8 days) than that of similar laser myringotomies (19.5 days). The mode of laser delivery did not have an effect on the closure rate. Kidney shaped CO2 laser myringotomies stayed patent significantly longer (mean 25.8 days) than circular (mean 11.4 days). The patency of smaller semicircular laser myringotomies was significantly longer than that of larger circular. The results indicate that certain geometries as well as use of the CO2 laser delays the closure of myringotomy. When myringotomy is performed for therapeutic reasons not only the size but also the shape should be considered as a factor for extending its length of patency. In the future CO2 laser may become an instrument for creating reliable myringotomies of different shapes and sizes.
Valtonen, Hannu J.; Poe, Dennis S.; Perrault, Donald F., Jr.; Lombardo, Igino; Pankratov, Michail M.; Shapshay, Stanley M.
Developmental Effects of SSRI's - Lessons learned from Animal Studies
Selective serotonin reuptake inhibitors (SSRI's) are utilized in the treatment of depression in pregrant and lactating women. SSRI's may be passed to the fetus through the placenta and the neonate through breastfeeding, potentially exposing them to SSRIs during peri and postnatal development. However, the long-term effects of this SSRI exposure are still largely unknown. The simplicity and genetic amenability of model organisms is a significant advantage to work with humans. This review will assess the current research done in animals that sheds light on the role of serotonin during development and the possible effects of SSRIs. Experimental studies in rodents show that administration of SSRIs during a key developmental window creates changes in brain circuitry and maladaptive behaviors that persist into adulthood. Similar changes result from the inhibition of serotonin transporter or monoamine oxidase, implicating these two regulators of serotonin signaling in developmental changes. Understanding the role of serotonin in brain development is critical to identifying the possible effects of SSRI exposure.
Borue, Xenia; Chen, John; Condron, Barry G.
Animal experimentation in Japan: regulatory processes and application for microbiological studies.
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. PMID:17416418
Takahashi-Omoe, H; Omoe, K
All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species.
Abnormalities of peripheral tolerance are thought to contribute to the pathogenesis of a number of inflammatory, autoimmune and neoplastic diseases of both humans and animals. Furthermore, the induction of allograft tolerance is the 'holy grail' of clinical transplantation. Of the various mechanisms underlying peripheral tolerance, regulatory T cells (Tregs) have risen to particular prominence. Various Treg subsets have been characterised, including naturally occurring cells that develop along a regulatory lineage in the thymus and induced cells that arise in the periphery from conventional T cell precursors. The transcription factor Forkhead box (Foxp3) serves a crucial role in stabilising the Treg transcriptome and is a faithful marker of peripheral Tregs in the mouse, though its expression is somewhat more promiscuous in man. Regulatory T cells display a wide spectrum of suppressive and cytotoxic mechanisms and may convert to specific T helper cell subsets in response to appropriate inflammatory cues. Although knowledge of Tregs in domestic animal species is still in its infancy, a growing body of literature is accumulating in the dog, cat, pig, cow, sheep and horse. We highlight our own and other studies of Tregs in the dog, an important veterinary species and a model for a number of human diseases. The ethos of 'One Health, One Medicine' is anticipated to accelerate efforts to close the knowledge gap between domestic animal and mainstream species in this field. We predict that the prodigious pace of research into Tregs will continue unabated for years to come, fuelled by the exciting therapeutic potential of these cells. PMID:21093606
Garden, O A; Pinheiro, D; Cunningham, F
Dialog with black box: using Information Theory to study animal language behaviour
In this review, three main experimental approaches for studying animal language behaviour are compared: (1) direct decoding\\u000a of animals' communication, (2) the use of intermediary languages to communicate with animals and (3) application of ideas\\u000a and methods of the Information Theory for studying quantitative characteristics of animal communication. Each of the three\\u000a methodological approaches has its specific power and specific
Zhanna Reznikova
Swedish pig producers and their perspectives on animal welfare: a case study
Purpose – The purpose of this paper is to identify the views of Swedish pig producers concerning animal welfare, the schemes practised for animal welfare in Sweden, and the ramifications of animal welfare for Swedish retailers and consumers. Design\\/methodology\\/approach – The Swedish study for animal welfare covers a pig-production sector of 2,794 producers (2005). The pig production study was one
Karl Bruckmeier; Madeleine Prutzer
Molecular epidemiological studies on animal trypanosomiases in Ghana
Background African trypanosomes are extracellular protozoan parasites that are transmitted between mammalian hosts by the bite of an infected tsetse fly. Human African Trypanosomiasis (HAT) or sleeping sickness is caused by Trypanosoma brucei rhodesiense or T. brucei gambiense, while African Animal Trypanosomiasis (AAT) is caused mainly by T. vivax, T. congolense, T. simiae,T. evansi and T. brucei brucei. Trypanosomiasis is of public health importance in humans and is also the major constraint for livestock productivity in sub-Saharan African countries. Scanty information exists about the trypanosomiasis status in Ghana especially regarding molecular epidemiology. Therefore, this study intended to apply molecular tools to identify and characterize trypanosomes in Ghana. Methods A total of 219 tsetse flies, 248 pigs and 146 cattle blood samples were collected from Adidome and Koforidua regions in Ghana in 2010. Initial PCR assays were conducted using the internal transcribed spacer one (ITS1) of ribosomal DNA (rDNA) primers, which can detect most of the pathogenic trypanosome species and T. vivax-specific cathepsin L-like gene primers. In addition, species- or subgroup-specific PCRs were performed for T. b. rhodesiense, T. b. gambiense, T. evansi and three subgroups of T. congolense. Results The overall prevalence of trypanosomes were 17.4% (38/219), 57.5% (84/146) and 28.6% (71/248) in tsetse flies, cattle and pigs, respectively. T. congolense subgroup-specific PCR revealed that T. congolense Savannah (52.6%) and T. congolense Forest (66.0%) were the endemic subgroups in Ghana with 18.6% being mixed infections. T. evansi was detected in a single tsetse fly. Human infective trypanosomes were not detected in the tested samples. Conclusion Our results showed that there is a high prevalence of parasites in both tsetse flies and livestock in the study areas in Ghana. This enhances the need to strengthen control policies and institute measures that help prevent the spread of the parasites.
Animal models for the study of Helicobacter pylori infection.
The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural. PMID:24864111
Miszczyk, Eliza; Walencka, Maria; Miko?ajczyk-Chmiela, Magdalena
Host-Parasite Relationships in Experimental Airborne Tuberculosis I. Preliminary Studies in BCG-Vaccinated and Nonvaccinated Animals
Smith, D. W. (University of Wisconsin, Madison), E. Wiegeshaus, R. Navalkar, and A. A. Grover. Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and nonvaccinated animals. J. Bacteriol. 91:718–724. 1966.—Previous studies from this laboratory on immunogenicity and allergenicity of defatted mycobacterial vaccines involved subcutaneous challenge of guinea pigs and killing of the animals 6 weeks later to evaluate the amount of disease. This type of experiment has discontinued in this laboratory in favor of an airborne challenge type of experiment, with the advantages that animals can be challenged with small numbers of bacilli by a natural route, and the number of primary lesions, the rate of spread from those lesions, and the rate of bacillary multiplication can be used to evaluate protection. Experiments to determine uniformity of infection showed that a fair degree of uniformity resulted when seven guinea pigs were exposed simultaneously, and were studied 3 weeks later to determine numbers of primary lesions and bacilli in the tissues. A less satisfactory degree of uniformity was obtained when more animals were exposed at one time. BCG-vaccinated and nonvaccinated animals were studied to determine the earliest time and the optimal time for killing the animals to detect the effects of vaccination. In guinea pigs, the degree of protection assessed by lesion counts is time-dependent, but the degree of protection assessed by viable counts of bacilli in the tissues was relatively constant 3 to 12 weeks after infection. Mice vaccinated subcutaneously with BCG were not protected against infection at any interval between 2 and 19 weeks. Guinea pigs vaccinated subcutaneously with the same lot of vaccine were protected as judged by counts of viable bacilli in the tissues 3 weeks after infection. Images
Smith, D. W.; Wiegeshaus, E.; Navalkar, R.; Grover, A. A.
Attitudes towards wild animal conservation: a comparative study of the Yi and Mosuo in China
Global wild animal resources are declining due to various pressures, which will greatly affect local biodiversity and ecosystem services. Understanding local people's attitudes towards wild animal conservation in high biodiversity areas is of major importance for conservation efforts. Sampling and questionnaire survey methods were employed to examine people's attitudes toward wild animal conservation in a comparative case study of two
Naiyi Yang; Endi Zhang; Min Chen
Fermentation of animal components in strict carnivores: a comparative study with cheetah fecal inoculum
The natural diet of felids contains highly digestible animal tissues but also fractions resistant to small intestinal digestion, which enter the large intestine where they may be fermented by the resident microbial population. Little information exists on the microbial degradability of animal tissues in the large intestine of felids consuming a natural diet. This study aimed to rank animal substrates
S. Depauw
A Comparative Study on the Felting Propensity of Animal Fibers
The felting propensity of different animal fibers, particularly alpaca and wool, has been examined. The Aachen felting test method was employed. 1 g of each type of fiber was soaked in 50 ml of wetting solution and agitated in a dyeing machine to make felt balls. The diameter of each ball was measured in nine directions and the ball density
Xin Liu; Xungai Wang
Road-Killed Animals as Resources for Ecological Studies.
ERIC Educational Resources Information Center
Summarizes 19 literature sources identifying road-killed vertebrates and frequency of kill by numbers. Examples of how these animals can be incorporated into curricula (integrating biology, society, people, and values) are given, followed by an illustrated example of how a road-killed raccoon's skull demonstrated a human/wildlife interaction prior…
Adams, Clark E.
Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation
Objective: To examine the effects of C-phycocyanin, a pigment found in blue-green algae which acts as an antioxidant in vitro and in vivo, in different animal models of inflammation.¶Material: Male Sprague Dawley rats and OF1 mice were used.¶Treatments: Oedema was induced by: a) AA (0.5 mg\\/ear) or TPA (4 7g\\/ear) in the mouse ear b) carrageenan injection (0.1 mL of
C. Romay; N. Ledón; R. González
A three-generation animal study of the biological effects of low-frequency electromagnetic fields
Three successive generation of CFW mice have been chronically exposed to a 25-mT (250.000 mG), 60-Hz electromagnetic field for prolonged periods of time. At the end of the exposure period, a complete autopsy was performed and the tissue from the main organs was processed for histopathological examination. The results reveal that a significant number of the animals in the exposed
W. Z. Fam; E. L. Mikhail
Molecular Heterogeneities of Adipose Depots - Potential Effects on Adipose-Muscle Cross-Talk in Humans, Mice and Farm Animals
Adipose tissue is considered as a major endocrine organ that secretes numerous proteins called adipokines. The heterogeneous nature of adipose tissue in different parts of the body suggests respective heterogeneity of proteomes and secretomes. This review consolidates knowledge from recent studies targeting the diversity of different adipose depots affecting the pattern of secreted adipokines and discusses potential consequences for the cross-talk between adipose and skeletal muscle in humans, rodent models and farm animals. Special attention is paid to muscle-associated fat depots like inter- and intramuscular fat that become focus of attention in the context of the rather new notion of skeletal muscle as a major endocrine organ. Understanding the complexity of communication between adipocytes and skeletal muscle cells will allow developing strategies for improvement of human health and for sustainable production of high quality meat.
Komolka, Katrin; Albrecht, Elke; Wimmers, Klaus; Michal, Jennifer J.; Maak, Steffen
Methyl isocyanate: reproductive and development toxicology studies in Swiss mice
Studies were conducted in Swiss (CD-1) mice to evaluate the potential of inhaled vapors of methyl isocyanate (MIC) to affect reproduction and development. Inhaled MIC at concentrations of 0, 1, or 3 ppm, 6 hr per day during days 14 through 17 of gestation caused a significant increase in the number of dead fetuses at birth and caused a significant decrease in neonatal survival during lactation. In contrast, exposure of male and female mice to 1 or 3 ppm given 6 hr per day for 4 consecutive days had no effect on reproduction during mating trials conducted 1, 8, and 17 weeks after the exposure period. Similarly, there was no evidence of a dominant lethal effect in exposed male mice.
Schwetz, B.A.; Adkins, B. Jr.; Harris, M.; Moorman, M.; Sloane, R.
Studies on the Biodisposition of Organophosphates in Mice.
National Technical Information Service (NTIS)
The biodisposition of radioactivity was studied in mice following the i.v. administration of 3H-DFP (1 mg/kg). EH-DFP penetrated tissues rapidly so that within 1 min of drug administration, maximal levels of radioactivity were found in brain, lung, heart ...
B. R. Martin
Subchronic toxicity study in mice fed Spirulina maxima
The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue–green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w\\/w) for 13 weeks. The alga ingestion had no
M Salazar; E Mart??nez; E Madrigal; L. E Ruiz; G. A Chamorro
Animal models for studying miscarriage: Illustration with study of drinking water disinfection by-products Authors & affiliations: Narotsky1, M.G. and S. Bielmeier Laffan2. 1Reproductive Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Tri...
[The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 10. Cooperative immune reactions in different generations of mice].
The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and "graft versus host" disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antiviral antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms. PMID:1745757
Savtsova, Z D; Kovbasiuk, S A; Iudina, O Iu; Zaritskaia, M Iu; Voe?kova, I M; Orlovski?, A A; Indyk, V M; Serkiz, Ia I
A study on radiation sterilization of SPF animal feed
NASA Astrophysics Data System (ADS)
SPF animal feed could be infected with various microorganisms in the crushing or granulating process. Fumigation with chemicals is generally employed for sterilization of feeds, but owing to low permeability of the chemicals, this sterilization method is not very good, and there may be residual chemicals in the feed. Research results of sterilization by radiation show that irradiation by 60Co gamma rays will reduce infections for SPF animals. 8 kGy can kill microoganisms in the feed with satisfactory efficiency. After the irradiation treatment with different doses, the changes of nutrient components in the feeds, such as crude fats, coarse fibres, calcium, phosphorus, salts and amino acids, were not found to change in our tests.
Chen, Qinglong; Ha, Yiming; Chen, Zhijun
Second hand smoke and COPD: lessons from animal studies
Exposure to second hand smoke is a major cause of chronic obstructive pulmonary disease (COPD) in the non-smoker. In this review we explore the use of animal smoke exposure models and their insight into disease pathogenesis. The methods of smoke exposure, including exposure delivery systems, are described. Key findings from the acute and chronic smoke exposure models are outlined, including descriptions of the inflammation processes, proteases involved, oxidative stress, and apoptosis. Finally, alternatives to rodent models of lung disease are presented.
Goldklang, Monica P.; Marks, Sarah M.; D'Armiento, Jeanine M.
Histological and ultrastructural study of the inflammation evoked by Paracoccidioides brasiliensis antigen in previously immunized mice.
Bentonite particles uncoated and coated with soluble antigen of Paracoccidioides brasiliensis (Pb) were intravenously injected into mice with and without previous immunization with Pb antigen. The inflammatory reaction around the bentonite emboli in small lung vessels was quantitated and morphologically studied by light and electron (EM) microscopy, 2 to 8 days after challenge. In control nonimmunized animals, coated and uncoated bentonite particles caused mild and nonspecific inflammation made up by macrophages. By EM, they formed loosely aggregated clusters with cytoplasm containing few organelles and borders without interdigitation. In immunized mice injected with coated bentonite particles, the inflammatory area was significantly greater than that in nonimmunized animals in all periods of study with maximum difference at day 2. The inflammatory process at days 2 and 4 was characterized as mature granulomata, composed of macrophages with great number of organelles in the cytoplasm, large euchromatic nuclei and prominent nucleoli. Altogether these findings indicated a lesion with high metabolic activity, compatible with a granulomatous hypersensitivity reaction. At days 6 and 8, there was a change from mature to epithelioid granulomata, well demonstrated by EM which showed macrophages with characteristically interdigitated cytoplasmic borders. The results strengthen the importance of cellular immunity in the genesis of epithelioid granuloma in paracoccidioidomycosis and reinforce the usefulness of the present model in studies of the inflammatory cellular sequency and events in this mycosis. PMID:2739693
Defaveri, J; Martin, L C; Franco, M
[The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 9. The morphofunctional indices of the immunocompetent organs in mice].
The permanent action of small doses of low-intensity radiation on the immune status of 2.5-3.5 month CC57W mice has been investigated. Total doses of internal and external irradiation were about few cGy. The permanent action of low-level radiation on the experimental animals of the first and fourth generations was shown to change spleen and lymph nodes weights and the count of lymphocytes isolated from these organs. Cellularity and DNA synthesis in the lymph-node lymphocytes and their proliferative response to polyclonal mitogens also changed. The alterations in the parameters that characterized T-lymphocyte population were statistically significant. PMID:1745756
Savtsova, Z D; Kovbasiuk, S A; Iudina, O Iu; Zaritskaia, M Iu; Voe?kova, I M; Indyk, V M; Serkiz, Ia I
Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.
Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid ?-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid ?-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid ?-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid ?-glucosidase and the common mutations underlying Gaucher disease. PMID:23642305
Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A
Animal models of pancreatitis: Can it be translated to human pain study?
Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.
Zhao, Jing-Bo; Liao, Dong-Hua; Nissen, Thomas Dahl
A preliminary study on progesterone antioxidation in promoting learning and memory of young ovariectomized mice
Introduction The aim of this preliminary study was to evaluate the effect of long-term progesterone (P4) treatment on structural and functional deficits associated with the hippocampus. Material and methods Mice served as sham controls or were bilaterally ovariectomized (Ovx), and a 90-day regimen of placebo or P4 was applied to the animal. After the administration, the acquisition and retrieval of mice in contextual fear conditioning (CFC) and a water maze were examined. Hippocampal tissues from some mice in each group were stained with cresyl violet, and the remainder were taken for determining the antioxidant power. Results Compared with placebo controls, the time spent on freezing was higher and the latencies were longer for mice given high-dose P4 (HP) (p < 0.05) in CFC, and the HP group also had longer searching time spent in the target quadrant (p < 0.05) in the water maze. Compared with placebo controls, the cell number of hippocampus CA1, CA3 and DG was significantly higher in the HP group (p < 0.05), and the thickness of the cell layer in CA1 and DG was also higher in the HP group (p < 0.05). All the oxidative stress biomarkers show that the antioxidative activity in hippocampus tissue from the HP and LP groups is higher than that in placebo controls (p < 0.05). Conclusions Ovx impairs learning and memory of mice, which can be rescued by a long-term regimen of HP via its antioxidant effects.
He, Lu; Yang, Hui; Zhai, Li-dong; Shao, Heng; Li, Yun-sheng
MR studies of brain oedema in the developing animal.
Assessment of perinatal brain oedema is complicated by normal changes in brain water that accompany the marked physiological, biochemical and morphological alterations occurring during this phase of development. Multiexponential analysis of transverse decay curves (TDCs), derived from 128 echo CPMG images, of white matter (WM) made oedematous by either exposure of animals to triethyltin (TET) or cryogenic cortical lesions revealed a second, slower decay component not apparent in controls. More significantly, an obvious difference was noted between the TET and cryogenic lesion fast decay components which might serve as a basis to differentiate non-invasively cytotoxic and vasogenic oedemas. PMID:2089948
Lorenzo, A V; Mulkern, R V; Wong, S T; Colucci, V M; Jolesz, F A
Sensitization of guinea pigs to picric acid was obtained by application of oil solutions to the skin, preferably on inflamed sites or by treatment with a compound of picric acid with n-butyl-p-aminobenzoate. The lesions obtained in sensitive animals on superficial administration bore resemblance to human eczema. It seems probable that picric acid sensitization is an instance where a substance does not sensitize directly but after conversion into a more reactive compound, a principle which should be of wider application to instances where the original substance does not readily form conjugates.
Landsteiner, K.; Di Somma, A. A.
Tumor radiosensitization with concomitant bone marrow radioprotection: a study in mice using diethyldithiocarbamate (DDC) under oxygenated and hypoxic conditions
The authors have established, both in vitro and in vivo, that Diethyldithiocarbamate (DDC) protects mammalian cells from radiation. The in vivo protection, when non-toxic concentrations of DDC are present one-half hour before irradiation, is reflected by a dose modification factor (DMF) of 1.9 based on LD/sub 50/30/ and 1.5 using survival of CFU/sub s/ as an endpoint. The DMF (LD/sub 50/30/) for DDC in air breathing animals, previously established as 1.9 can be contrasted with a DMF, obtained in the present study, of 1.2 for animals irradiated in the hypoxic state. Moreover the DMF (CFU/sub s/ survival) previously established at 1.5 for air breathing animals, can be compared to a value of 1.3, obtained in the present study, for mice irradiated under hypoxic conditions. Modification of the dose response by DDC, for bone marrow and tumor, was also examined in animals bearing a RIF sarcoma. Although protection of the bone marrow was confirmed (DMF = 2.1), the striking finding was that the tumor cells were sensitized, in both air breathing and nitrogen breathing animals, by the addition of DDC one-half hour before the radiation exposure. The tumor radiosensitization was even more marked in the nitrogen breathing mice, in which a factor of 10 difference in survival was noted, together with a tendency towards greater sensitization at radiation doses in the clinical range.
Evans, R.G.
High-frequency oscillatory ventilation: What large-animal studies have taught us!
Background Much of the information on the physiologic effects, mechanisms of gas exchange, and potential utility of high-frequency oscillation (HFO) has been acquired in animal studies. Specifically, large animal data have been useful in assessing adult application because large animals present many of the same concerns and challenges as adults. Objective To review the literature on HFO testing in large animal models, identifying contributions to the understanding of mechanisms of action and the physiology of HFO. Results Large animal studies have clarified the mechanisms of gas exchange during HFO, identified approaches to setting mean airway pressure based on lung mechanics, and identified a potentially better approach to applying partial liquid ventilation. Conclusion The study of HFO in large animal models has been essential to our understanding of the optimal approach to applying HFO in human studies.
Kacmarek, Robert M.; Malhotra, Atul
Swiss bare mice: a suitable model for transcutaneous in vivo Raman spectroscopic studies of breast cancer.
Breast cancer is the most common cancer affecting females worldwide. As early detection results in better prognosis, screening tools for breast cancer are being explored. Raman spectroscopy, a rapid, objective, and noninvasive tool, has shown promising results in the diagnosis of several cancers including breast cancer. For development as a screening tool, a study of spectral signatures associated with breast cancer progression is imperative. However, such studies are not possible in human subjects. Hence, there is a need for a suitable animal model, which is conducive to transcutaneous in vivo Raman spectroscopic measurements of breast with minimal interference from skin and hair and has contribution from functional mammary epithelium of breast. In this study, rodent models like C57, Swiss albino, Swiss bare, agouti mice, and Sprague-Dawley rats were evaluated. Among these models, transcutaneous breast spectra of hairless Swiss bare mice have the best signal-to-noise ratio and were closest to reported ex vivo as well as intraoperative in vivo human breast spectra. Principal component-linear discriminant analysis of several anatomical sites confirms minimal skin interference and suggests contribution from functional mammary epithelium of breast. Moreover, transcutaneous spectra from normal breast and breast tumors of Swiss bare mice could be classified with 99% efficiency, which is better than the previous reports. Thus, Swiss bare mice model may be better suited for transcutaneous in vivo Raman spectroscopic studies of breast physiology and pathology, especially breast cancer. Prospectively, in addition to cancer progression, breast-to-bone metastasis can also be studied, since these anatomical sites can be uniquely classified. PMID:23708992
Bhattacharjee, T; Kumar, Piyush; Maru, G; Ingle, A; Krishna, C Murali
Toward an Understanding of Human Violence: Cultural Studies, Animal Studies, and the Promise of Posthumanism
ERIC Educational Resources Information Center
On January 3, 2012, the "New York Times" featured an article announcing the emergence of the new interdisciplinary field of animal studies, which is spreading across college campuses in new course offerings, new majors, and new undergraduate and graduate programs. This new field grows out of, on the one hand, a long history of scientific research…
Worsham, Lynn
Intracerebral Hemorrhage in Mice: Model Characterization and Application for Genetically Modified Mice
Gene knockout or transgenic animals may assist in elucidating the mechanisms of brain injury after intracerebral hemorrhage (ICH). However, almost all commercially available transgenic or knockout animals are mice. The purpose of this study was to develop an ICH model in mice and to investigate the influence of gender and complement C5 genetic differences on outcome after ICH. Male and
Takehiro Nakamura; Guohua Xi; Ya Hua; Timothy Schallert; Julian T. Hoff; Richard F. Keep
Validation Studies on Blood Collection from the Jugular Vein of Conscious Mice
A method for blood collection from the jugular vein of mice without anesthesia was compared with a tail-incision technique. Jugular vein blood collection allowed withdrawal of almost 15% of the circulating blood volume at a time in less than 1 min. Hemolysis, hematocrit, and plasma thrombin–antithrombin complexes (a marker of blood coagulation) were higher in samples collected from the tail vein than the jugular vein. Mice produced similar plasma corticosterone levels after serial blood collection by either method. Tail incision led to a slight but significant increase in C-reactive protein levels. Using the jugular venipuncture technique, we then performed a pharmacokinetic study and an oral glucose tolerance test. Plasma concentrations of levofloxacin, an antimicrobial agent, were dose-dependently elevated after oral administration, and linear increases in Cmax and AUC were observed. We also confirmed that overall glucose excursion is significantly decreased in mice treated with exendin 4, a glucagon-like peptide 1 agonist. These results indicate that the jugular venipuncture is a useful technique from the point of view of no requirement for anesthetics, serial blood collection at short intervals, large volume of blood collection, quality of sample and animal welfare. This technique is of particular interest for studies that examine time-dependent changes in blood variables.
Shirasaki, Yasufumi; Ito, Yoshihiro; Kikuchi, Miho; Imamura, Yuichiro; Hayashi, Toshiaki
The use of alert behaving mice in the study of learning and memory processes.
The availability of transgenic mice that mimic human neurodegenerative processes has made it necessary to develop new recording and stimulating techniques capable of being applied in this species. We have studied here the motor learning and memory capabilities of wild-type and transgenic mice with deficits in cognitive functions, using classical conditioning procedures. We have developed an electrical shock/SHOCK paradigm corresponding to a trace classical conditioning; that is, a learning task involving the cerebral cortex, including the hippocampus. The conditioning procedure is a modification of the air-puff/AIR-PUFF conditioning (Gruart et al., J. Neurophysiol. 74:226, 1995). Animals were implanted with stimulating electrodes in the supraorbitary branch of the trigeminal nerve and with recording electrodes in the orbicularis oculi muscle. Computer programs were developed to quantify the appearance and evolution of eyelid conditioned responses. According to the present results, the classical conditioning of eyelid responses appears to be a suitable (associative) learning procedure to study learning capabilities in genetically-modified mice. PMID:15325961
Rodríguez-Moreno, Antonio; Domínguez Del Toro, Eduardo; Porras-García, Elena; Delgado-García, José M
Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies
Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, 'gold standard' multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2?0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of ?0.2 mm. In serial animal imaging studies, the positioning reproducibility within ?0.8 mm could be obtained.
Zhang, Mutian; Huang, Minming; Le, Carl; Zanzonico, Pat B; Claus, Filip; Kolbert, Katherine S; Martin, Kyle; Ling, C Clifton; Koutcher, Jason A; Humm, John L
A search filter for increasing the retrieval of animal studies in Embase.
Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments. PMID:21890653
de Vries, Rob B M; Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel
Animal models for human Metapneumovirus (HMPV) infections
Since its detection in 2001 the human Metapneumovirus (HMPV), a member of the Paramyxoviridae family, was observed to be a serious pathogen in human respiratory infections during childhood. Meanwhile, several animal models have been established to study the virus-host interactions and pathogenic effects. Mainly, small laboratory animals like mice and cotton rats have been used, although the usage of these
Oliver Schildgen; Arne Simon; John Williams
Toxicity studies in mice of Commiphora molmol oleo-gum-resin.
Acute (24 h) and chronic (90 days) oral toxicity studies on Commiphora molmol (oleo-gum-resin) were carried out in mice. Dosages in acute study were 0.5, 1.0 and 3 g/kg, while in chronic study dosage was 100 mg/kg per day. All external morphological, biochemical and haematological changes, in addition to body and vital organ weights were recorded. There was no significant difference in mortality in acute or chronic treatment as compared to controls. At the end of the treatment, weight gain in the treated as well as control group was significant. There was a significant increase in weight of testes, caudae epididymides and seminal vesicles in C. molmol treated group. Biochemical studies revealed no differences in C. molmol treated animals, however, haematological studies revealed a significant increase in RBC and haemoglobin levels as compared to the control group. C. molmol failed to show any spermatotoxic effects. PMID:11390128
Rao, R M; Khan, Z A; Shah, A H
Light microscopic study of the effect of new antischistosmal drug (myrrh extract) on the liver of mice.
The efficacy of purified oleo-resin extract of myrrh derived from Commiphora molmol tree, (known as Mirazid) was studied against an Egyptian strain of Schistosoma mansoni in mice. Seventy adult male mice were used in this study. They were divided into 4 groups: G.I: consisted of control noninfected nontreated mice. G.II: comprised the noninfected treated mice and was subdivided into two subgroups, subgroup II-A: included mice which received Myrrh extract dissolved in cremophore EL and subgroup II-B: included mice which were treated with cremophore EL. G.III: consisted of the infected nontreated animals and G.IV: included infected mice which were treated with myrrh extract. The drug was given 8 weeks post infection in a dose of 500 mg/kg body weight/day for 5 successive days. All animals were sacrificed after 12 weeks from the beginning of the experiment. Liver paraffin sections were prepared and stained with H&E, Masson's Trichrome stain, PAS stain and Wilder's technique. A morphometric study was performed for the mean number and perimeter of the granulomas. Area percentage of the total collagen content around central veins as well as in portal areas was also estimated. The livers of the animals in G.II which received either myrrh extract (subgroup II-A) or cremophore EL (subgroup II-B) showed a more or less normal histological profile when compared to G.I (noninfected-nontreated group). G.IV (Infected treated G.) showed complete preservation of the hepatic architecture. Most of the hepatocytes appeared almost normal. The reticular network in the central part of the granulomas as well as in the portal tracts appeared rarefied. The hepatic reticular network was preserved. A significant decrease in the number and size of granulomas with significant reduction in the collagen content deposition in portal tracts and around central veins was detected when compared to G.III (infected nontreated mice). The data of this study proved the efficacy of myrrh as a promising antischistosomal drug. PMID:16333904
Massoud, Ahmed M A; el Ebiary, Faika H; Ibrahim, Suzi H
Individual study of chromium in the stainless steel implants degradation: An experimental study in mice
To study the accumulation and the histological effects in mice organs caused by hexavalent chromium, one of the corrosion products released from AISI 316L stainless steel implants, mice groups were subcutaneously injected with a metallic solution of chromium during a certain period of time. Similar injections were made with HBSS (Hank's Balanced Salt Solution) in other groups to be used
Maria do Carmo Pereira; Maria de Lourdes Pereira; Joăo Paulo Sousa
Electron microscopic radioautographic study on protein synthesis in mitochondria of binucleate hepatocytes of aging mice.
In order to study the aging changes of intramitochondrial protein synthesis in mouse hepatocytes, 10 groups of aging mice, each consisting of three individuals, total 30, from fetal day 19 to postnatal year 2, were injected with 3H-leucine, a protein precursor, sacrificed 1 h later, and the liver tissues processed for electron microscopic radioautography. On electron microscopic radioautograms obtained from each animal, the numbers of mitochondria, the numbers of labeled mitochondria, and the mitochondrial labeling index labeled with 3H-leucine that showed protein synthesis in each hepatocyte, both mononucleate and binucleate cells, were counted and the averages in respective aging groups were compared. From the results, it was demonstrated that the numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein syntheses in both mononucleate and binucleate hepatocytes of mice at various ages increased due to development of animals. The numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein synthesis in binucleate hepatocytes were more than those of mononucleate hepatocytes at the same aging stages. PMID:17619783
Nagata, Tetsuji
Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities
Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice.
Guruprasad, K. P.; Mascarenhas, Roshan; Gopinath, P. M.; Satyamoorthy, K.
Family of Enhanced Photoacoustic Imaging Agents for High Sensitivity and Multiplexing Studies in Living Mice
Photoacoustic imaging is a unique modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a family of novel photoacoustic contrast agents that are based on the binding of small optical dyes to single walled carbon nanotubes (SWNT-dye). We synthesized five different SWNT-dye contrast agents using different optical dyes, creating five "flavors" of SWNT-dye nanoparticles. In particular, SWNT that were coated with either QSY21 (SWNT-QSY) or Indocyanine Green (SWNT-ICG) exhibited over 100-times higher photoacoustic contrast in living animals compared to plain SWNTs, leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the ?v?3 integrin, which is associated with tumor angiogenesis. Intravenous administration of these tumor-targeted imaging agents to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. Finally, we were able to spectrally separate the photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected subcutaneously with both particles in the same location, opening the possibility for multiplexing in vivo studies.
de Zerda, Adam; Bodapati, Sunil; Teed, Robert; May, Salomon Y.; Tabakman, Scott M.; Liu, Zhuang; Khuri-Yakub, Butrus T.; Chen, Xiaoyuan; Dai, Hongjie; Gambhir, Sanjiv S.
A study of quantification of aortic compliance in mice using radial acquisition phase contrast MRI
NASA Astrophysics Data System (ADS)
Spatiotemporal changes in blood flow velocity measured using Phase contrast Magnetic Resonance Imaging (MRI) can be used to quantify Pulse Wave Velocity (PWV) and Wall Shear Stress (WSS), well known indices of vessel compliance. A study was conducted to measure the PWV in the aortic arch in young healthy children using conventional phase contrast MRI and a post processing algorithm that automatically track the peak velocity in phase contrast images. It is shown that the PWV calculated using peak velocity-time data has less variability compared to that using mean velocity and flow. Conventional MR data acquisition techniques lack both the spatial and temporal resolution needed to accurately calculate PWV and WSS in in vivo studies using transgenic animal models of arterial diseases. Radial k-space acquisition can improve both spatial and temporal resolution. A major part of this thesis was devoted to developing technology for Radial Phase Contrast Magnetic Resonance (RPCMR) cine imaging on a 7 Tesla Animal scanner. A pulse sequence with asymmetric radial k-space acquisition was designed and implemented. Software developed to reconstruct the RPCMR images include gridding, density compensation and centering of k-Space that corrects the image ghosting introduced by hardware response time. Image processing software was developed to automatically segment the vessel lumen and correct for phase offset due to eddy currents. Finally, in vivo and ex vivo aortic compliance measurements were conducted in a well-established mouse model for atherosclerosis: Apolipoprotein E-knockout (ApoE-KO). Using RPCMR technique, a significantly higher PWV value as well as a higher average WSS was detected among 9 months old ApoE-KO mice compare to in wild type mice. A follow up ex-vivo test of tissue elasticity confirmed the impaired distensibility of aortic arteries among ApoE-KO mice.
Zhao, Xuandong
Juvenile animal studies for the development of paediatric medicines: a description and conclusions from a European Medicines Agency workshop on juvenile animal testing for nonclinical assessors.
A workshop organised by the European Medicines Agency involved assessors and experts present in a Nonclinical Working Group evaluating juvenile animal studies for Paediatric Investigation Plans in collaboration with the Paediatric Committee and the Safety Working Party of the Committee for Human Medicinal Products. The objective of the workshop was to analyse which juvenile animal studies proposals were received and agreed by the Paediatric Committee, to check consistency and how to apply the existing European guideline on juvenile animal studies. A comparison of main organ system development in man vs. animal species was presented to guide the review and to support species selection and protocol design. An analysis of juvenile animal studies included in finalised PIP's was also presented. Out of 109 paediatric investigation plans finalised between November 2008 and March 2009, 43 included one or more juvenile animal studies. In most cases the preferred species was the rat; one species only was requested to be studied (20/22), but in a minority two species were required (2/22). When deciding on the characteristics of the juvenile animal studies, such as age of animals at study start, the age of the children targeted by the medicine was considered. It is expected that the increasing experience gained by Applicants and Regulators will allow further refining the criteria for these juvenile animal studies. Further research on this topic is highly encouraged in the European Regulatory framework. PMID:20632393
Silva-Lima, Beatriz; Due Theilade-Thomsen, Mette; Carleer, Jacqueline; Vidal, Jean-Marc; Tomasi, Paolo; Saint-Raymond, Agnes
[Formal sample size calculation and its limited validity in animal studies of medical basic research].
Animal studies are highly relevant for basic medical research, although their usage is discussed controversially in public. Thus, an optimal sample size for these projects should be aimed at from a biometrical point of view. Statistical sample size calculation is usually the appropriate methodology in planning medical research projects. However, required information is often not valid or only available during the course of an animal experiment. This article critically discusses the validity of formal sample size calculation for animal studies. Within the discussion, some requirements are formulated to fundamentally regulate the process of sample size determination for animal experiments. PMID:24326876
Mayer, B; Muche, R
Review of certain low-level ionizing radiation studies in mice and guinea pigs
Starting in the early 1940s, Egon Lorenz and collaborators at the National Cancer Institute began an extended study of chronic low-level ionizing radiation effects in what was then the tolerance range for man. Observations on life span, body weight and radiation carcinogenesis, among others, were made in mice, guinea pigs and rabbits. At the then-permissible exposure level, 0.1 R** per 8-h day until natural death, experimental mice and guinea pigs had a slightly greater mean life span compared to control animals. In addition, there was marked weight gain during the growth phase in both species. Increased tumor incidence was also observed at the 0.1-R level in mice. The primary hypothesis for increased median life span has been rebound regenerative hyperplasia during the early part of the exposure; in the presence of continuing injury, there is physiological enhancement of defense mechanisms against intercurrent infection. The body weight gain has not been explained. 32 references.
Congdon, C.C.
Nude mice as models for human leukemia studies.
Human leukemic promyelocytes of the HL-60 line were grown as tumors in nude mice and studied. A single nonmetastatic granulocytic sarcoma developed after subcutaneous inoculation with HL-60 cells. Some exceeded 5 cm in size. Almost all mice developed tumors after initial priming with cyclophosphamide. Older sarcomas showed viable tumor islands in necrotic and fibrotic tissue. Some tumors appeared greenish. Histologic and electron-microscopic analysis demonstrated large, vaguely outlined cells in poorly vascularized sheets. The cells displayed high nucleocytoplasmic ratios, basophilic granular cytoplasms lacking Auer rods, and enzymes characteristic of cultured HL-60 promyelocytes. Some tumor cells also demonstrated monocyte/macrophage enzymes, such as butyrate esterase. Induced HL-60 tumors also corresponded morphologically to a human subcutaneous promyelocytic tumor specimen. Comparative cytologic studies of induced HL-60 tumors in nude mice and cultured HL-60 cells revealed virtual identity, suggesting the nude mouse tumor as a useful model for in vivo studies of human leukemic cells. Images Figure 1 Figure 2 Figure 3
Potter, G. K.; Shen, R. N.; Chiao, J. W.
Variations in study design are typical for toxicogenomic studies, but their impact on gene expression in control animals has not been well characterized. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Scienc...
Animals in the Classroom: A Guide for Teachers. Elementary Science Study.
ERIC Educational Resources Information Center
This guide is designed to encourage people to keep animals of all kinds in the classroom and to use them in teaching language arts, mathematics, and social studies, as well as science and nature study. The booklet is divided into four sections. The first section contains an account of a year with desert animals in an ungraded classroom of six- to…
Gillmor, Mary S.; And Others
The Value of Animations in Biology Teaching: A Study of Long-Term Memory Retention
Previous work has established that a narrated animation is more effective at communicating a complex biological process (signal transduction) than the equivalent graphic with figure legend. To my knowledge, no study has been done in any subject area on the effectiveness of animations versus graphics in the long-term retention of information, a primary and critical issue in studies of teaching
Danton H. O'Day
Applications of ultrasmall superparamagnetic iron oxide contrast agents in the MR study of animal models
Ultrasmall superparamagnetic iron oxide nanoparticles have been widely used during the past decade as MR intravascular contrast agents in the study of animal models. Such agents enhance both T1 and T2\\/T2* relaxation, although for animal studies it is the later type of enhancement that is most commonly exploited. Their strong microscopic intravascular susceptibility effect enables the local blood volume distribution
Ed X. Wu; Haiying Tang; Jens H. Jensen
Assessment of aortic pulse wave velocity by ultrasound: a feasibility study in mice
NASA Astrophysics Data System (ADS)
Pulse wave velocity (PWV) is considered a surrogate marker of arterial stiffness and could be useful for characterizing cardiovascular disease progression even in mouse models. Aim of this study was to develop an image process algorithm for assessing arterial PWV in mice using ultrasound (US) images only and test it on the evaluation of age-associated differences in abdominal aorta PWV (aaPWV). US scans were obtained from six adult (7 months) and six old (19 months) wild type male mice (strain C57BL6) under gaseous anaesthesia. For each mouse, diameter and flow velocity instantaneous values were achieved from abdominal aorta B-mode and PW-Doppler images; all measurements were obtained using edge detection and contour tracking techniques. Single-beat mean diameter and velocity were calculated and time-aligned, providing the lnD-V loop. aaPWV values were obtained from the slope of the linear part of the loop (the early systolic phase), while relative distension (relD) measurements were calculated from the mean diameter signal. aaPWV values for young mice (3.5±0.52 m/s) were lower than those obtained for older ones (5.12±0.98 m/s) while relD measurements were higher in young (25%±7%) compared with older animals evaluations (15%±3%). All measurements were significantly different between the two groups (P<0.01 both). In conclusion, the proposed image processing technique well discriminate between age groups. Since it provides PWV assessment just from US images, it could represent a simply and useful system for vascular stiffness evaluation at any arterial site in the mouse, even in preclinical small animal models.
Faita, Francesco; Di Lascio, Nicole; Stea, Francesco; Kusmic, Claudia; Sicari, Rosa
Nicotinic acid inhibits hepatic APOA gene expression: studies in humans and in transgenic mice[S
Elevated plasma lipoprotein(a) (LPA) levels are recognized as an independent risk factor for cardiovascular diseases. Our knowledge on LPA metabolism is incomplete, which makes it difficult to develop LPA-lowering medications. Nicotinic acid (NA) is the main drug recommended for the treatment of patients with increased plasma LPA concentrations. The mechanism of NA in lowering LPA is virtually unknown. To study this mechanism, we treated transgenic (tg) APOA mice with NA and measured plasma APOA and hepatic mRNA levels. In addition, mouse and human primary hepatocytes were incubated with NA, and the expression of APOA was followed. Feeding 1% NA reduced plasma APOA and hepatic expression of APOA in tg-APOA mice. Experiments with cultured human and mouse primary hepatocytes in addition to reporter assays performed in HepG2 cells revealed that NA suppresses APOA transcription. The region between ?1446 and ?857 of the human APOA promoter harboring several cAMP response element binding sites conferred the negative effect of NA. In accordance, cAMP stimulated APOA transcription, and NA reduced hepatic cAMP levels. It is suggested that cAMP signaling might be involved in reducing APOA transcription, which leads to the lowering of plasma LPA.
Chennamsetty, Indumathi; Kostner, Karam M.; Claudel, Thierry; Vinod, Manjula; Frank, Sasa; Weiss, Thomas S.; Trauner, Michael; Kostner, Gerhard M.
The effect of nanoparticle properties, detection method, delivery route and animal model on poly(lactic-co-glycolic) acid nanoparticles biodistribution in mice and rats.
Abstract A review of poly(lactic-co-glycolic) acid (PLGA) nanoparticle (NP) biodistribution was conducted with the intent of identifying particle behavior for drug delivery applications. Databases such as Science Direct and Web of Science were used to locate papers on biodistribution of intravenous (i.v.) and orally delivered PLGA NPs in mice and rats. The papers included in the review were limited to those that report biodistribution data in terms of % dose particles/g tissue in the liver, kidney, spleen, lung, heart and brain. Noted trends involved particle behavior based on individual organ, particle size, animal model, type of indicator (entrapped versus covalently linked) and method of delivery (oral or i.v.). The liver showed the highest uptake of particles in mice, and the lung showed the highest uptake in rats. Minimal amounts of particles were detected in both the heart and brain of rats and mice. In rats, the concentration of particles approached 0% dose/g or decreased significantly over 24?h after administration of a single dose of particles. Higher concentrations of smaller particles were evident in the liver, kidney and spleen. Orally delivered drugs showed little to no uptake within the 24?h analysis when compared with i.v. delivered NPs. Differences in particle concentrations between rats and mice were also observed as expected when expressed as % dose/g organ. Particles with covalently linked indicators showed lower concentrations in tissues than particles with physically entrapped indicators. Further research on oral delivery of PLGA NPs as well as distribution beyond 24?h is needed to fully understand particle behavior in vivo for successful application of NPs in drug delivery. PMID:24303927
Simon, Lacey C; Sabliov, Cristina M
Behavioral studies of the effects of moderate oligemic hypoxia caused by bilateral clamping of carotid arteries in mice. Impairment of spatial working memory.
The experiments carried out on Albino Swiss mice indicated that bilateral clamping of carotid arteries (BCCA) for 30 min caused no neuronal damage but produced an increase in GABA content in the hippocampus, striatum and frontal cortex. The behavioral studies have shown that BCCA did not influence the motor coordination, the spontaneous locomotor activity, the reactivity to pain and the cataleptic response to haloperidol of the mice. However, a significant increase in amphetamine-induced hyperactivity was observed after BCCA. In mice, BCCA did not impair long-term memory and spatial working memory, reflected by alternation behavior in the Y-maze. The same dose of scopolamine impaired the working memory in mice which underwent BCCA much more than sham-operated controls. Naftidrofuryl improved the working memory in mice subjected to BCCA as measured 48 h after the surgery. Pretreatment with naftidrofuryl protected the animals against the impairment of alternation behavior caused by scopolamine administration. PMID:10091712
Jó?wiak, L; Sieklucka-Dziuba, M; Kleinrok, Z
A comparative approach to the study of Keeper-Animal Relationships in the zoo.
Research on intensively farmed animals over the past 25 years has shown that human-animal interactions, by affecting the animal's fear of humans, can markedly limit the productivity and welfare of farm animals. This article begins to explore some of the factors that need to be considered to investigate Keeper-Animal Relationships (KARs) in the zoo. In the mid-1990s, a large body of multi-institutional data on zookeepers and animals was collected from 46 Zoos. Using standardized questionnaires, 82 keepers rated how they behaved towards animals, their husbandry routine, how the animal responds to them and to other people, and provided information about themselves. These data include 219 individuals of four endangered species: black rhinoceros, cheetah, maned wolf, and great hornbill. At each zoo, keepers were also videotaped calling to their animals in order to directly observe animal responses to keeper behaviors. Principle Components Analysis reduced eight animal variables to three components and ten keeper variables to five components. Scores for animals and for keepers were calculated on these components and compared, according to five predictions based on models of human-animal interactions in the literature. Animal responses to keepers varied along three dimensions: Affinity to Keeper, Fear of People, and Sociable/Curious. Animal scores of Fear of People were significantly and positively correlated with independent measures of poor welfare from two later studies: fecal corticoid concentrations for 12 black rhinos and "tense-fearful" scores for 12 cheetahs. (1) Significant species differences were found for Affinity to Keeper and Fear of People, and the interaction of these two dimensions of animal response to keepers appears to be species-specific. (2) The quality of KAR is influenced by whether the zookeeper goes in the enclosure with the animal or not, the frequency and time of feeding, and keeper visibility to the animal. Among keepers who go in with their animals, a significant negative correlation between Frequency of Feeding/Early Feedtime and average Affinity to Keeper of their animals, and a positive correlation between Keeper Experience and their animals' Fear of People, indicates that certain zoo keeping styles or habits among experienced keepers might be aversive and increase fear among animals. (3) Keepers who locomote or make unexpected noises when calling their animals elicit increased aggression or apprehension from maned wolves and cheetahs. (4) Wild-born black rhino and parent-reared maned wolf have significantly less affinity to keepers than their captive-born or hand-reared counterparts, but neither differs in Fear of People. (5) Keeper-animal relationships are likely to be reciprocal as evidenced by a negative correlation of Job Satisfaction with animal Fear of People. Future research directions are discussed with respect to assessment of keeper attitudes and behaviors, animal fear, positive measures of welfare, and positive reinforcement training. PMID:19885915
Carlstead, Kathy
Olfactory and Visuospatial Learning and Memory Performance in Two Strains of Alzheimer's Disease Model Mice--A Longitudinal Study
Using a longitudinal study design, two strains of Alzheimer's disease (AD) model mice, one expressing ?-amyloid plaques and one expressing Tau protein-associated neurofibrillary tangles were assessed for olfactory and visuospatial learning and memory and their performance compared to that of age-matched controls. No significant difference between AD and control mice was found in the initial set of olfactory tasks performed at 6 months of age whereas both strains of AD mice performed significantly poorer than the controls in visuospatial learning at this age. Subsequent tests performed on the same individual animals at 7, 8, 9, 11, 13, 15, and 18 months of age also failed to find systematic differences in olfactory performance between AD and control mice. In contrast, the AD mice performed consistently poorer than the controls in visuospatial re-learning tests performed at these ages. With most olfactory tasks, both AD and control mice displayed a marked decrease in performance between testing at 15 and 18 months of age. These results show that the two strains of AD model mice do not display an olfactory impairment in a time course consistent with human AD, but are impaired in visuospatial capabilities. The marked age-related changes observed with the olfactory tasks in both AD and control mice suggest that the observed lack of an AD-related olfactory impairment is not due to an insensitivity of the tests employed. Rather, they suggest that the olfactory system of the two AD mouse model strains may be surprisingly robust against AD-typical neuropathologies.
Osterman, Hanna; Willhite, David; Laska, Matthias
A step-by-step guide to systematically identify all relevant animal studies.
Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056
Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel
A step-by-step guide to systematically identify all relevant animal studies
Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future.
Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel
Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies
The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors including histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.
Ward, J.M.; Quander, R.; Devor, D.; Wenk, M.L.; Spangler, E.F.
Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.
The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value. PMID:22571623
de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert
Functional Changes in Neocortical Activity in Huntington's Disease Model Mice: An in vivo Intracellular Study
Studies of animal models of Huntington's disease (HD) have revealed that neocortical and neostriatal neurons of these animals in vitro exhibit a number of morphological and physiological changes, including increased input resistance and changes in neocortical synaptic inputs. We measured the functional effects of polyglutamate accumulation in neocortical neurons in R6/2 mice (8–14 weeks of age) and their age-matched non-transgenic littermates using in vivo intracellular recordings. All neurons showed spontaneous membrane potential fluctuations. The current/voltage and the firing properties of the HD neocortical neurons were significantly altered, especially in the physiologically relevant current range around and below threshold. As a result, membrane potential transitions from the Down state to Up state were evoked with smaller currents in HD neocortical neurons than in controls. The excitation-to-frequency curves of the HD mice were significantly steeper than those of controls, indicating a smaller input–output dynamic range for these neurons. Increased likelihood of Down to Up state transitions could cause pathological recruitment of corticostriatal assemblies by increasing correlated neuronal activity. We measured coherence of the in vivo intracellular recordings with simultaneously recorded electrocorticograms. We found that the peak of the coherence at <5?Hz was significantly smaller in the HD animals, indicating that the amount of coherence in the state transitions of single neurons is less correlated with global activity than non-transgenic controls. We propose that decreased correlation of neocortical inputs may be a major physiological cause underlying the errors in sensorimotor pattern generation in HD.
Stern, Edward A.
Imaging Primary Lung Cancers in Mice to Study Radiation Biology
Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.
Kirsch, David G., E-mail: email@example.com [David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC (United States); Grimm, Jan [Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA (United States); Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Guimaraes, Alexander R. [Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA (United States); Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); Wojtkiewicz, Gregory R. [Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA (United States); Perez, Bradford A. [Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC (United States); Santiago, Philip M. [David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA (United States); Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)
Animal models for the study of perinatal hypoxic-ischemic encephalopathy: a critical analysis
We critically evaluated various design features from 292 animal studies related to perinatal hypoxic-ischemic encephalopathy (HIE). Rodents were the most frequently used animals in HIE research (26%), followed by piglets (23%) and sheep (22%). Asphyxia with or without ischemia was the most predominant method of producing experimental brain damage, but there were significant variations in specific details, particularly regarding the
Tabasam Roohey; Tonse N. K. Raju; Anastasia N. Moustogiannis
Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain
ERIC Educational Resources Information Center
This paper explores the validity of performance management regimes for quality assuring animal health regulation by comparing the results of tests for bovine tuberculosis (bTB) between male and female vets. In doing so it hopes to present some practical solutions to the regulation of animal disease and encourage further sociological study of the…
Enticott, Gareth
Ethics and Animal Welfare Evaluations in South East Asian Zoos: A Case Study of Thailand
Concern for zoo animals is palpable throughout society in many countries in South East Asia. It is important to understand problems of animal welfare in order for zoos to make significant improvement in maintaining high standards. With a case study of 3 zoos in Thailand, this article presents results for the first time on how ethics and wel- fare evaluations
Govindasamy Agoramoorthy; Bernard Harrison
The acute effects of corticosteroids on cognition: integration of animal and human model studies
Cognitive deficits following acute administration of corticosteroids have been described in experimental animals and humans. In both populations, an inverted-U shape relationship has been reported between the dose of corticosteroids administered and the nature and extent of the cognitive deficits induced by corticosteroids. Further studies in animals have revealed a two-level recognition system for adrenal steroids, which was later more
Sonia J. Lupien; Bruce S. McEwen
Studies of Hard and Soft Tissue Elemental Compositions in Mice and Rats Subjected to Simulated Microgravity
NASA Astrophysics Data System (ADS)
Microgravity has profound effects on skeletal as well as other body systems. To investigate the effect of microgravity, we have used a NASA validated Hind-limb suspension (HLS) animal model of simulated weightlessness. Groups of mice and rats were subjected to hind limb suspension between 1 and 14 days while the control groups were maintained without suspension for the same duration. To study the effect of diet, some groups of animals were fed on a special diet with defined composition. At term, the animals were sacrificed and the tibia, femur, and skull bones were collected. In addition, soft tissues from pancreas and muscles were also collected. All of the bones and tissues samples were analyzed for elemental analysis using Energy Dispersive Spectroscopy (EDS) equipped on a Scanning Electron Microscope (SEM). In the EDS, 10-20 keV electrons bombarded the samples and a Si (Li) detector measured K-, L- and M-shell x-rays. Independently, X-Ray Fluorescence (XRF) provided the data for comparison and normalization. Flame software, with Fuzzy Logic, was used to form elemental ratios. Elemental analysis of bone samples indicated a variation in the compositional ratios of calcium, potassium, oxygen and carbon in the leg bones and skulls of the HLS versus control specimens. These variations showed dependence on sample position in the bone.
Mehta, Rahul; Lane, Ryan A.; Fitch, Hannah M.; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal
Seprafilm® adhesion barrier: (1) a review of preclinical, animal, and human investigational studies.
The aim of this study was to provide a single site resource for investigators, clinicians, and others seeking preclinical, animal, and human investigational studies concerning the postsurgical, anti-adhesion barrier Seprafilm™ (Genzyme Corporation, Cambridge, MA). All published preclinical, animal, human extra-abdominal research as of July 2011 have been summarized and included in this document. Searches of Medline and EMBASE Drugs and Pharmaceuticals databases were conducted for original preclinical, animal, and human extra-abdominal studies involving Seprafilm. Preclinical, animal, and extra-abdominal human investigational studies are the study selection for this manuscript. Intraabdominal use is discussed in the accompanying manuscript. Data extraction includes systematic manuscript review. Summary of preclinical, animal, and extra-abdominal human investigational use of Seprafilm by surgical discipline were gathered for data synthesis. The clinical use of Seprafilm, which was approved by the FDA for intra-abdominal procedures, is supported by preclinical and animal studies relating to general surgical and obstetrical/gynecological applications. Findings from preclinical, animal, and human investigational studies at other sites throughout the body raises the potential for additional human clinical trials to assess efficacy and safety following surgical procedures at non-abdominal locations. PMID:22837732
Diamond, Michael P; Burns, Ellen L; Accomando, Beverly; Mian, Sadiqa; Holmdahl, Lena
Case Study: An Unusual Case of Animal Reproduction
NSDL National Science Digital Library
This is a case study for undergraduate and graduate students in biology and can be adapted for anatomy, physiology, and/or anatomy and physiology courses. In particular this case study explores anatomy and physiology associated with reproductive biology. Users of the National Center for Case Study Teaching in Science will be required to register (free) to gain access to the answer key (and must be of teaching status to receive the key). Included in the resource are the case overview, objectives, case study, teaching notes and answer key.
Joann B Powell (Clark Atlanta University Biological Sciences)
Inhalation of diesel exhaust is associated with the development of asthma as well as other adverse health effects. Studies have also demonstrated that diesel exhaust induces pulmonary changes that worsen asthmatic responses to respiratory allergens. This paper describes the des...
Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies
Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable.
Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies.
Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable. PMID:21943025
Shineman, Diana W; Basi, Guriqbal S; Bizon, Jennifer L; Colton, Carol A; Greenberg, Barry D; Hollister, Beth A; Lincecum, John; Leblanc, Gabrielle G; Lee, Linda Bobbi H; Luo, Feng; Morgan, Dave; Morse, Iva; Refolo, Lorenzo M; Riddell, David R; Scearce-Levie, Kimberly; Sweeney, Patrick; Yrjänheikki, Juha; Fillit, Howard M
Plants or animals - which do junior high school students prefer to study?
NASA Astrophysics Data System (ADS)
This research addressed the following questions: (1) Which science topic do junior high school students prefer to study - plants or animals? (2) Is their preference related to the variables of grade level and sex of student? Public school students from grades 7, 8, and 9 in Avoca, New York participated in the study. Findings show that 9th grade students have a greater interest in biological science topics than do students in the other grades studied. Girls are more interested in biological science topics than boys are. Girls also showed a significant preference for animals over plants. As a group, junior high school students revealed that they prefer animal study over plant study. About half of the student responses categorized as biological science did not express a clear-cut preference for either plants or animals. A caution about generalizability is expressed. Interviews of students suggest that the following characteristics of animals are important determinants of preferences: Animals move, eat, have eyes for sight, communicate by sound, exhibit behaviors that are fun to watch, have short and observable live cycles, interact with humans, can learn, have mates, give birth, and raise their young. It was obvious that most students think of mammals when they hear the term animal.
Wandersee, James H.
1. Intravenous injection into mice of phase I Bordetella pertussis vaccine resulted in a striking hyperleucocytosis with a predominating lymphocytosis. Intraperitoneal inoculation was less effective, and subcutaneous administration was inactive. 2. Active immunization prevented the hyperleucocytosis; passive immunization was less effective. 3. Reticuloendothelial blockage reduced the effect of the vaccine. 4. Extirpation of the spleen or thymus did not alter the leucocyte response. 5. Histologic studies suggested that the increase in circulating lymphocytes resulted from release of cells from lymphoid organs, including the thymus.
Morse, Stephen I.
Stress and alcohol interactions: animal studies and clinical significance.
Alcohol is frequently consumed for stress relief, but the individual determinants and the temporal course of stress-induced alcohol use are not well understood. Preclinical studies may help shed light on these factors. We synthesize here the findings from numerous rodent studies of stress and alcohol interactions. Stress-induced alcohol consumption is age-dependent, has a high genetic load, and results from an interaction of the stress and reward systems. Specifically, glucocorticoids, acting within the nucleus accumbens (NAc), are important mediators of this stress-induced alcohol intake. In addition, increased activation of the corticotropin-releasing hormone (CRH) system within the extended amygdala appears to mediate stress-induced relapse. Finally, these preclinical studies have helped to identify several attractive targets for novel treatments of alcohol abuse and addiction. PMID:24636458
Spanagel, Rainer; Noori, Hamid R; Heilig, Markus
Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.
Fink, Mitchell P
Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels
Objective In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute to arterial blood pressure regulation by producing membrane hyperpolarization and smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary circulation is not fully established. Using mice with genetically encoded deficit of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension. Approach and Result Male wild type and KCa3.1?/?/KCa2.3T/T(+DOX) mice were exposed to chronic hypoxia for four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The KCa3.1?/?/KCa2.3T/T(+DOX) mice developed structural alterations in the heart with increased right ventricular wall thickness as well as in pulmonary vessels with increased lumen size in partially- and fully-muscularized vessels and decreased wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated the gene expression of the KCa2.3 channel by twofold in wild type mice and increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was reduced by 2.5-fold in chronic hypoxic mice of either genotype. Conclusion Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia-induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and increased NS309-induced relaxation in wild-type mice point to a novel mechanism to counteract pulmonary hypertension and to a potential therapeutic utility of KCa2.3/KCa3.1 activators for the treatment of pulmonary hypertension.
Sadda, Veeranjaneyulu; Nielsen, Gorm; Hedegaard, Elise R?ge; Mogensen, Susie; Kohler, Ralf; Simonsen, Ulf
A Case Study of Memory Loss in Mice
NSDL National Science Digital Library
This case study looks at an animal model in the study of Alzheimer's disease. Students will identify which components of the scientific method are used in the case. The lesson may be used in a variety of science courses, both for science majors and non-majors; it would be appropriate for upper level high school or lower level undergraduate classes. The case study and teaching notes may be downloaded in PDF format. The site also includes a section for instructor feedback where general comments may be read and contributed.
Hudecki, Michael S.
Studies on oxygen transfer process in animal cell culture bioreactor.
The oxygen transfer rates were investigated systematically in the CellCul-20A bioreactor with the device of cage aeration in this paper. The temperature, rotating speed, aeration rate and foam breaker, which affected the rate of oxygen transfer were studied, respectively. The mass transfer rate increased significantly with the aeration while the foam breaker had a negative effect on kLa, especially in a cell culture medium with 5% (v/v) calf serum. The oxygen transfer coefficients of surface and deep aerations were correlated, based on the experimental data. PMID:8155835
Wang, S; Chen, Y; Pan, H; Yu, J
Animal models of atherosclerosis
In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research.
Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H
A better prognosis for genetic association studies in mice.
Although inbred mouse strains have been the premier model organism used in biomedical research, multiple studies and analyses have indicated that genome-wide association studies (GWAS) cannot be productively performed using inbred mouse strains. However, there is one type of GWAS in mice that has successfully identified the genetic basis for many biomedical traits of interest: haplotype-based computational genetic mapping (HBCGM). Here, we describe how the methodological basis for a HBCGM study significantly differs from that of a conventional murine GWAS, and how an integrative analysis of its output within the context of other 'omic' information can enable genetic discovery. Consideration of these factors will substantially improve the prognosis for the utility of murine genetic association studies for biomedical discovery. PMID:22118772
Zheng, Ming; Dill, David; Peltz, Gary
Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models
There are exciting new advances in multiple sclerosis (MS) resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR) is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS) studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.
Nathoo, Nabeela; Yong, V. Wee; Dunn, Jeff F.
Studies of pancreatic carcinogenesis in different animal models.
Pancreatic carcinomas can be induced in rat, guinea pig and hamster by a variety of carcinogens. The types of neoplasms which arise vary with the species of rodent. In the rat, they consist exclusively of acinar cells, in the other species the lesions are adenocarcinomas resembling those derived from pancreatic ductules and ducts, those in hamster more so than in guinea pigs. Careful sequential studies in the guinea pig and hamster suggest that acinar cells together with ductular and duct cells are involved in the genesis of duct adenocarcinomas. In each rodent model, the acinar cell appears to be quite sensitive to continued exposure to carcinogen. In each instance, acini undergo modulation, and in the guinea pig and hamster, permanent metaplastic transformation to ductlike structures. Such cells assume an enhanced capacity for cell proliferation which persists following cessation of carcinogen treatment. Other studies suggest that adult pancreatic acinar cells possess a surprising degree of plasticity. Their involvement in the pathogenesis of neoplasms resembling pancreatic ducts is not unlike other carcinogenic sequences where extensive cell modulation and metaplasia precede and are an integral part of the neoplastic transformation. Images FIGURE 1. FIGURE 2. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9.
Scarpelli, D G; Rao, M S; Reddy, J K
Titanium dioxide as an osteoconductive material: an animal study.
The purpose of the present study was to evaluate the biocompatibility and osteoconductive potential of pure and pigment forms of titanium dioxide. Pure and pigment forms of titanium dioxide were incorporated into prepared bur holes in the femur bone of rabbits. Implantation was done on six Albino rabbits which were sacrificed at the end of 3rd, 4th and 5th months after implantation. Radiographic, histologic and scanning electron microscopic evaluations of the implanted sites were performed. Heamatologic and soft tissue response to these materials were also evaluated. The results showed that both pure and pigment forms of titanium dioxide are biocompatible and have good osteoconductive properties. It was concluded that titanium dioxide can be effectively used in the augmentation of osseous defects and inadequate ridge forms. PMID:24431717
Harshakumar, Karunakaran; Nair, K Chandrasekharan; Paulose, N George; Nair, Vivek V; Prasanth, V; Krishnan, Aswathi
[Protective effect of the aerosol immunization of mice with the polycomponent vaccine Immunovac VP-4 after the challenge of the animals with Klebsiella pneumoniae virulent strain].
Used four schemes of the administration of the preparation with different time of the exposition of the animals in an aerosol chamber were tested with their subsequent intraperitoneal challenge with K. pneumoniae virulent strain K16. Irrespective of the number of immunization courses, the administration of the preparation made at intervals of 1 day, or daily, did not ensure any protective effect, but only led to an insignificant increase in their survival time in comparison with nonimmunized animals. After intervals between immunizations were increased to 3 days the protective effect of aerosol immumization was obtained (the survival rate was 65-80 % and considerably differed from that of the controls). The protective effect of aerosol immunization thus obtained was comparable with the effectiveness immunization made in a single subcutaneous injection. Aerosol immunization resulted in low antibody titers to the antigens contained in the vaccine, while after a single subcutaneous injection high antibody titers to Klebsiella and Proteus antigens were detected. The antigen-stimulated blast transformation of spleen lymphocytes in mice subjected to aerosol immunizations in 5 exposures was high. After subcutaneous immunization significant changes in such characteristics were detected on day 15. The data thus obtained were indicative of good prospects in the development Immunovac VP-4 as the medicinal form intended for use in aerosols. PMID:16532635
Solov'ev, K G; Kurbatova, E A; Egorova, N B; Uspenskaia, S N; Tret'iakova, A V; Varfolomeev, A N; Gruber, I M; Efremova, V N; Akhmatova, N K; Diadizhshev, N R; Akhmatova, I B; Diadishchev, N R; Semenova, I B; Cherkasova, L S; Semenov, B F; Borovik, R V
Proteomic study on gender differences in aging kidney of mice
Background This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Results This proteomic analysis detected age-related changes in protein expression in 55 protein-spots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES) of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on age-related changes in expression levels of proteins and related modifications. This pilot study is still far from providing candidates for aging-biomarkers. However, we suggest that the analysis of these proteins could suggest mechanisms of cellular aging in kidney, and improve the kidney selection for transplantation.
Amelina, Hanna; Cristobal, Susana
Skin and bone integrated prosthetic pylon: a pilot animal study.
Direct skeletal attachment of limb prostheses is a viable alternative to traditional techniques that are based on a socket-residuum interface. Direct skeletal attachment may be a better or even the only method for patients with a very short residuum and high soft-tissue volume. The problem of integrating the prosthetic pylon with residual skin during direct skeletal attachment of a limb prosthesis has not been solved, and the use of a completely porous prosthetic pylon has not been the subject of focused, systematic research. In this in vivo study, we investigated cell (osteocyte, fibroblast, and keratinocyte) adhesion and penetration into the pores of a titanium pylon implanted in Wistar rats. The porous titanium pylon was implanted in the bone of the thigh residua of four rats. Electronic scanning and morphological analysis demonstrated integration of the pylon with the surrounding skin. These findings support the possibility of developing a natural barrier against the infection associated with direct skeletal attachment of limb prostheses. PMID:17123195
Pitkin, Mark; Raykhtsaum, Grigory; Galibin, Oleg V; Protasov, Mikhail V; Chihovskaya, Julie V; Belyaeva, Irina G
Acute Inhalation Toxicity of Saxitoxin to Mice.
National Technical Information Service (NTIS)
Systemic toxicity of saxitoxin (STX) in a variety of laboratory animals is well documented. Reports of toxicity from respiratory exposure, however, are negligible. In the study a concentration-response curve was determined for mice exposed to aerosols gen...
D. A. Cresia M. L. Neally
Gastric cancer: Animal studies on the risk of hypoacidity and hypergastrinemia
Gastric hypoacidity and hypergastrinaemia are seen in several conditions associated with an increased risk of gastric malignancy. Hypoacidity and hypergastrinaemia are closely related and their long-term effects are difficult to study separately in patients. Studies using animal models can provide valuable information about risk factors and mechanisms in gastric cancer development as the models allow a high degree of intervention when introducing or eliminating factors possibly affecting carcinogenesis. In this report, we briefly review findings from relevant animal studies on this topic. Animal models of gastric hypoacidity and hypergastrinaemia provide evidence hypergastrinaemia is a common causative factor in many otherwise diverse settings. In all species where sufficient hypoacidity and hypergastrinaemia have been induced, a proportion of the animals develop malignant lesions in the gastric oxyntic mucosa.
Fossmark, Reidar; Qvigstad, Gunnar; Waldum, Helge L
BLT humanized mice as model to study HIV vaginal transmission.
The majority of human immunodeficiency virus type 1 (HIV-1) infections occur by sexual exposure, and vaginal transmission accounts for more than half of all newly acquired infections. Studies of vaginal transmission of simian immunodeficiency virus to nonhuman primates (NHPs) have suggested an important role for immune cell trafficking in the establishment of infection as well is in the process of viral dissemination. However, NHP models do not permit the study of HIV transmission and dissemination. The improvement of humanized mouse models with robust human immune cell reconstitution of the female genital tract renders these mice susceptible to intravaginal HIV infection. Thus humanized mouse models of HIV vaginal infection will allow the study of the mechanisms involved in HIV transmission and dissemination in vivo. PMID:24151319
Deruaz, Maud; Luster, Andrew D
Dysbaric Osteonecrosis in Mice.
National Technical Information Service (NTIS)
The histopathology of dysbaric osteonecrosis and the influence of the number of exposures, compression rate, and obesity on the incidence and latency of the lesion were studied in 438 mice (2505 bones were examined). The animals were subjected to 75 psig ...
C. P. Chryssanthou
The fate of 14C-labeled allergens injected intradermally into guinea pigs, namely picryl chloride (PCl*) and 2:4 dinitrochlorobenzene (DNCB*), was followed during the induction period of delayed hypersensitivity. Both chemicals were applied in a single injection into one ear in amounts that approached their minimal sensitizing doses (PCl, 0.25 µg; DNCB, 5.0 µg). Radioactivity in the various tissues was determined by liquid scintillation counting after combustion of tissues to CO2 and H2O. The injected allergens seemed to leave the injection site in three phases. A large proportion of allergen escaped rapidly from the ear, about 50% within 3 hr in the case of PCl, within 15 min for DNCB, the difference probably reflecting their unequal reaction constants. Initially there was a "half-life" escape in 2.5 hr with injected dosage of 0.25 µg PCl and in 18 hr for 5.0 µg DNCB. This escape occurred via the regional veins and not via the lymphatics. Radioactive decomposition products of the allergens were already present in the urine within 3–4 hr. After 6–8 hr, the half-life time of escape lengthened to approximately 28 hr for both allergens used in their respective initial dosages, holding up to 2 days after which there occurred still further slowing; between 2 and 4 days the time was about 43 hr for PCl, much longer (72–88 hr?) for DNCB, apparently reflecting different physicochemical properties of this second fraction. Sensitization seemed to be connected with the portion that was present between 12 hr and 4 days of the induction period. It is not known how far the escape of radioactivity during this period may represent gradual hydrolysis of attached picryl and dinitrophenyl groupings, respectively, to form picric acid and dinitrophenol. Gradual accumulation of the second fraction in the regional lymph nodes could definitely be excluded. It was noted that no hypersensitivity arose and essentially no depot of radioactivity existed between 12 hr and 4 days when DNCB was injected in a dose of 0.25 µg, owing to its ready escape from the ear; but 20 times as much DNCB caused sensitization and provided about the same fixed depot as 0.25 µg of picryl chloride. After delayed hypersensitivity had been established, traces of radioactivity were still measurable at the site. This third fraction, probably representing a different coupling product, escaped at a very low rate and was traceable up through several weeks. No demonstrable radioactivity could be detected in thymus, spleen, and mesenteric nodes when examined at short intervals between ˝ min and 17 days. In analogy with findings on transplantation "immunity" and with studies reported in the following paper, the induction of delayed hypersensitivity can be explained by encounters between lymphoid cells and the hapten complex which is found present in the local site for 4 days, in agreement with Medawar's concept of peripheral sensitization.
Macher, Egon; Chase, Merrill W.
NSDL National Science Digital Library
This animation demonstrates the stages of mitosis in an animal cell. Use the control buttons in the upper left to run the complete animation. Click on any intermediate stage (for example, Anaphase), and see a representative still frame.
Assessment of Myocardial Metabolism in Diabetic Rats Using Small-Animal PET: A Feasibility Study
This feasibility study was undertaken to determine whether kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats. Methods: All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabeticfattyrats(ZDF,fa\\/fa)and10leanlittermates(Lean,Fa\\/1) using 15O-water, 1-11C-glucose, 1-11C-acetate, and 1-11C- palmitate. Animals were
Michael J. Welch; Jason S. Lewis; Joonyoung Kim; Terry L. Sharp; Carmen S. Dence; Robert J. Gropler; Pilar Herrero
HEK293 cell culture media study towards bioprocess optimization: Animal derived component free and animal derived component containing platforms.
The increasing demand for biopharmaceuticals produced in mammalian cells has lead industries to enhance bioprocess volumetric productivity through different strategies. Among those strategies, cell culture media development is of major interest. In the present work, several commercially available culture media for Human Embryonic Kidney cells (HEK293) were evaluated in terms of maximal specific growth rate and maximal viable cell concentration supported. The main objective was to provide different cell culture platforms which are suitable for a wide range of applications depending on the type and the final use of the product obtained. Performing simple media supplementations with and without animal derived components, an enhancement of cell concentration from 2 × 10(6) cell/mL to 17 × 10(6) cell/mL was achieved in batch mode operation. Additionally, the media were evaluated for adenovirus production as a specific application case of HEK293 cells. None of the supplements interfered significantly with the adenovirus infection although some differences were encountered in viral productivity. To the best of our knowledge, the high cell density achieved in the work presented has never been reported before in HEK293 batch cell cultures and thus, our results are greatly promising to further study cell culture strategies in bioreactor towards bioprocess optimization. PMID:24183458
Liste-Calleja, Leticia; Lecina, Martí; Cairó, Jordi Joan
Microbiological monitoring of laboratory mice and biocontainment in individually ventilated cages: a field study
Summary Over recent years, the use of individually ventilated cage (IVC) rack systems in laboratory rodent facilities has increased. Since every cage in an IVC rack may be assumed to be a separate microbiological unit, comprehensive microbiological monitoring of animals kept in IVCs has become a challenging task, which may be addressed by the appropriate use of sentinel mice. Traditionally,
M Brielmeier; E Mahabir; J R Needham; C Lengger; P Wilhelm; J Schmidt
40 p53 heterozygous knockout mice and 40 p53 wild-type controls were exposed to 4 arsenicals in drinking water at a single dose, the maximum tolerated dose (MTD), in a chronic lifetime tumor bioassay, and animals were subjected to necropsy and limited pathologic examination of th...
The clastogenicity of ethyl acrylate (EA) was examined in vivo by injecting i.p. 5 male C57BL/6 mice per dose group with either 125, 250, 500, 1000 mg/kg EA dissolved in saline. wenty-four hours after injection, the animals were anesthetized, the spleens aseptically removed, and ...
Sample Size Considerations for One-to-One Animal Transmission Studies of the Influenza A Viruses
Background Animal transmission studies can provide important insights into host, viral and environmental factors affecting transmission of viruses including influenza A. The basic unit of analysis in typical animal transmission experiments is the presence or absence of transmission from an infectious animal to a susceptible animal. In studies comparing two groups (e.g. two host genetic variants, two virus strains, or two arrangements of animal cages), differences between groups are evaluated by comparing the proportion of pairs with successful transmission in each group. The present study aimed to discuss the significance and power to estimate transmissibility and identify differences in the transmissibility based on one-to-one trials. The analyses are illustrated on transmission studies of influenza A viruses in the ferret model. Methodology/Principal Findings Employing the stochastic general epidemic model, the basic reproduction number, R0, is derived from the final state of an epidemic and is related to the probability of successful transmission during each one-to-one trial. In studies to estimate transmissibility, we show that 3 pairs of infectious/susceptible animals cannot demonstrate a significantly higher transmissibility than R0?=?1, even if infection occurs in all three pairs. In comparisons between two groups, at least 4 pairs of infectious/susceptible animals are required in each group to ensure high power to identify significant differences in transmissibility between the groups. Conclusions These results inform the appropriate sample sizes for animal transmission experiments, while relating the observed proportion of infected pairs to R0, an interpretable epidemiological measure of transmissibility. In addition to the hypothesis testing results, the wide confidence intervals of R0 with small sample sizes also imply that the objective demonstration of difference or similarity should rest on firmly calculated sample size.
Nishiura, Hiroshi; Yen, Hui-Ling; Cowling, Benjamin J.
Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study
Background Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice's hematocrit was about 50% lower than that of controls (p?0.05) and their performance level was about 25% lower (p?0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio?>?1.4) and 115 were strongly down-regulated (normalized ratio?0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail.
Opportunities for the replacement of animals in the study of nausea and vomiting
Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms.
Holmes, AM; Rudd, JA; Tattersall, FD; Aziz, Q; Andrews, PLR
Rauscher leukemia as a model for cancer therapy studies. II. Variation in response of splenic CFU-S between normal and Rauscher leukemic mice following exposure to hydroxyurea
Normal mice and mice with advanced Rauscher leukemia were given a single dose of HU and evaluated for the effect of the drug on splenic CFU-S 4 and 16 hr later. Exposure to HU reduced the total number of CFU-S for both normal and leukemic mice by 50% at 4 hr. At 16 hr there was no recovery in CFU-S evident in the normal mouse. However, CFU-S levels in the spleens of the leukemic mice had recovered to nearly that existent before exposure to HU. Effects of HU on total splenic mass differed from that on the CFU-S. Recovery of total splenic mass was seen to have begun in normal animals by 16 hr after HU, while in the leukemic animals spleen size had receded further by 16 hr. The data suggest that, as in man, the hematopoietic recovery responses following exposure to chemotherapeutic drugs may be significantly different in Rauscher viral leukemic mice as compared to normal mice. The possible applicability of Rauscher leukemia as a model for leukemia therapy studies is briefly discussed.
Okunewick, J.P.; Meredith, R.F.; Brozovich, B.J.; Seeman, P.R.
Preflight studies on tolerance of pocket mice to oxygen and heat. II - Effects on lungs
NASA Technical Reports Server (NTRS)
An electron microscope examination was carried out on the lungs of 11 pocket mice (Perognathus longimembris) that breathed oxygen at 10 psi or 12 psi partial pressure over a period of 7 d, at the end of which time they were decompressed to sea-level O2 pressure, either suddenly or in 30, 60, or 90 min. Vesiculation was noted in the endothelium of the alveolar-capillary wall in most of the animals and, occasionally, blebbing. Some mitochrondria were swollen in a few of the animals. Alveolar exudate was, in general, sparse. Compared with the lungs of other rodents, the lungs of pocket mice appeared relatively resistant to the toxic effects of oxygen. This conclusion needs, however, to be tempered by the fact that 5% N2 was used in the tests reported here. Nonetheless, the results suggest that the oxygen pressures anticipated on the flight of Apollo XVII should be well tolerated by the pocket mice.
Harrison, G. A.; Corbett, R. L.; Klein, G.
Are Covered Stents Really Effective at Closing Esophagotracheal Fistulas? Results of an Animal Study
Purpose: To determine whether covered self-expanding metal stents successfully exclude experimentally created esophagotracheal fistulas.Methods: Esophagotracheal fistulas were surgically created in the upper third of the esophagus in 12 minipigs and immediately sealed by implantation of a covered self-expanding metal stent (20 mm expanded diameter) in the esophagus. Before the animals were killed, after 3, 7, 14, 28, 30, and 36 days, the position of the stent and the sealing of the fistula were monitored fluoroscopically. The esophagus, trachea, and both lungs were examined histologically.Results: Creation of an esophagotracheal fistula was successful in all cases. All fistulas were widely patent at autopsy. The technical success rate for stent deployment and initial sealing of the fistula was 100%. During follow-up, five stents migrated distally, but none into the stomach. Therefore, the fistula was no longer excluded in five animals. In seven animals the stent sealed the fistula until the death of the animal. Tracheal narrowing necessitated additional tracheal stenting in three animals. Two minipigs died due to aspiration of food. Histologic examination showed signs of aspiration in all animals with stents in place for longer than 2 weeks.Conclusion: This experimental animal study revealed worse results for sealing of esophagotracheal fistulas with covered self-expanding metal stents than have been reported for the clinical use of these devices.
Wagner, Hans-Joachim [Department of Diagnostic Radiology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Stinner, Benno [Department of General Surgery, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Barth, Peter [Department of Pathology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Klose, Klaus-Jochen [Department of Diagnostic Radiology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany)
Induction of PDK4 in the heart muscle of JVS mice, an animal model of systemic carnitine deficiency, does not appear to reduce glucose utilization by the heart
Pyruvate dehydrogenase kinase 4 (PDK4) mRNA has been reported as an up-regulated gene in the heart and skeletal muscle of carnitine-deficient juvenile visceral steatosis (JVS) mice under fed conditions. PDK4 plays an important role in the inhibition of glucose oxidation via the phosphorylation of pyruvate dehydrogenase complex (PDC). This study evaluated the meaning of increased PDK4 mRNA in glucose metabolism
Miharu Ushikai; Masahisa Horiuchi; Keiko Kobayashi; Sadayuki Matuda; Akio Inui; Toru Takeuchi; Takeyori Saheki
Antimicrobial peptides derived from different animals: comparative studies of antimicrobial properties, cytotoxicity and mechanism of action
Animals posses a large variety of antimicrobial peptides (AMPs) that serve as effective components in innate host defenses\\u000a against microbial infections. These antimicrobial peptides differ in amino acid composition, range of antimicrobial specificities,\\u000a hemolysis, cytotoxicity and mechanisms of action. This study was designed to evaluate their therapeutic potential of the following\\u000a six antimicrobial peptides initially found from animals: cecropin P1,
Fei-Fei Han; Yi-Fan Liu; Yong-Gang Xie; Yan-Hua Gao; Chao Luan; Yi-Zhen Wang
Small animal positron emission tomography during vagus nerve stimulation in rats: A pilot study
Vagus nerve stimulation (VNS) is an effective neurophysiological treatment for patients with refractory epilepsy, however, the mechanism of action remains unclear. Small animal positron emission tomography (PET) permits the monitoring of biochemical processes during multiple scans in the same animal. The aim of this pilot study was to explore the potential of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET to investigate the effect of acute
Stefanie Dedeurwaerdere; Bart Cornelissen; Koen Van Laere; Kristl Vonck; Eric Achten; Guido Slegers; Paul Boon
Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies
Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and
Mutian Zhang; Minming Huang; Carl Le; Pat B. Zanzonico; Filip Claus; Katherine S. Kolbert; Kyle Martin; C. Clifton Ling; Jason A. Koutcher; John L. Humm
Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate.
The survival of 90% of a tumor-bearing population treated with the complex Rh(2) (CF(3)CONH)(4) was examined and the pharmacological parameter Surv(90) determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv(90) dose of 3.8x 10(-5) mol/kg was found. PMID:18475875
Espósito, B P; Zyngier, S B; Najjar, R; Paes, R P; Ueda, S M; Barros, J C
Parasitological and morphological study of Schistosoma mansoni and diabetes mellitus in mice.
Schistosomes are blood-dwelling flukes which are highly dependent on the host metabolism. The aim of this study was to investigate possible relationship between streptozotocin-induced diabetes and the outcome of acute murine schistosomiasis mansoni. Male and female SW mice were treated by a single intraperitoneally injected dose of streptozotocin (180 mg/kg). Seven days after induction, both control and diabetic animals were infected with 70 Schistosoma mansoni cercariae (BH strain). Diabetics and their controls were weighed 45 days after birth and for the last time prior to killing. Susceptibility to infection was evaluated twice a week by quantifying fecal egg excretion 7-9 weeks post-infection by the Kato-Katz' thick smear method. Mice were euthanized the day after the last fecal examination was performed. Adult worms were recovered from the portal system and mesenteric veins, whereas liver and intestine were removed for enumeration of egg load. No differences in worm length or in measurements of the reproductive organs, tegument, and suckers were detected. Also oviposition was unaffected as the total number of eggs per female worm from the liver, the small and the large intestine was the same in both groups. An oogram evaluation revealed a lower percentage of mature (23.0% vs. 40.7%) and a higher percentage of immature (69.1% vs. 51.7%) eggs in the small intestine of the diabetic mice. We suggest that principally a hampered egg passage through the intestine tissue caused this reduction and that probably both the eggs and the impaired host response play a role. PMID:21708148
Hulstijn, Maarten; Barros, Lucas de Andrade; Neves, Renata Heisler; de Moura, Egberto Gaspar; Machado-Silva, José Roberto
Electron microscopic radioautographic study on mitochondrial DNA synthesis in adrenal cortical cells of developing and aging mice.
In order to study the aging changes of intramitochondrial DNA synthesis of mouse adrenal cortical cells, eight groups of developing mice, each consisting of three individuals (total 24), from fetal day 19 to postnatal newborn at days 1, 3, 9, 14, to adult at months 1, 2, and 6, were injected with 3H-thymidine, sacrificed 1 h later, and the adrenal tissues were fixed and processed for electron microscopic (EM) radioautography. On EM radioautograms obtained from each animal, the number of mitochondria and the mitochondrial labeling index labeled with 3H-thymidine showing DNA synthesis in each adrenal cortical cell, in three zones, were counted and the results in respective developing groups were compared. From the results, it was demonstrated that the numbers of mitochondria in the three zones, the zona glomerulosa, fasciculata, and reticularis, of mice at various ages increased from fetal day 19 to postnatal month 6 due to development and aging of animals, respectively, while the number of labeled mitochondria and the labeling index of intramitochondrial DNA syntheses incorporating 3H-thymidine increased from fetal day 19 to postnatal month 2, reaching the maxima, and decreased to month 6. It was shown that the activity of intramitochondrial DNA synthesis in the adrenal cortical cells in developing and aging mice changed due to aging. PMID:18661056
Nagata, Tetsuji
Fermentation of animal components in strict carnivores: a comparative study with cheetah fecal inoculum.
The natural diet of felids contains highly digestible animal tissues but also fractions resistant to small intestinal digestion, which enter the large intestine where they may be fermented by the resident microbial population. Little information exists on the microbial degradability of animal tissues in the large intestine of felids consuming a natural diet. This study aimed to rank animal substrates in their microbial degradability by means of an in vitro study using captive cheetahs fed a strict carnivorous diet as fecal donors. Fresh cheetah fecal samples were collected, pooled, and incubated with various raw animal substrates (chicken cartilage, collagen, glucosamine-chondroitin, glucosamine, rabbit bone, rabbit hair, and rabbit skin; 4 replicates per substrate) for cumulative gas production measurement in a batch culture technique. Negative (cellulose) and positive (casein and fructo-oligosaccharides; FOS) controls were incorporated in the study. Additionally, after 72 h of incubation, short-chain fatty acids (SCFA), including branched-chain fatty acids (BCFA), and ammonia concentrations were determined for each substrate. Glucosamine and glucosamine-chondroitin yielded the greatest organic matter cumulative gas volume (OMCV) among animal substrates (P < 0.05), whereas total SCFA production was greatest for collagen (P < 0.05). Collagen induced an acetate production comparable with FOS and a markedly high acetate-to-propionate ratio (8.41:1) compared with all other substrates (1.67:1 to 2.97:1). Chicken cartilage was rapidly fermentable, indicated by a greater maximal rate of gas production (R(max)) compared with all other substrates (P < 0.05). In general, animal substrates showed an earlier occurrence for maximal gas production rate compared with FOS. Rabbit hair, skin, and bone were poorly fermentable substrates, indicated by the least amount of OMCV and total SCFA among animal substrates (P < 0.05). The greatest amount of ammonia production among animal substrates was measured after incubation of collagen and rabbit bone (P < 0.05). This study provides the first insight into the potential of animal tissues to influence large intestinal fermentation in a strict carnivore, and indicates that animal tissues have potentially similar functions as soluble or insoluble plant fibers in vitro. Further research is warranted to assess the impact of fermentation of each type of animal tissue on gastro-intestinal function and health in the cheetah and other felid species. PMID:22287677
Depauw, S; Bosch, G; Hesta, M; Whitehouse-Tedd, K; Hendriks, W H; Kaandorp, J; Janssens, G P J
Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovirus infections. Recent advances in biotechnology have permitted the study of many of the animal cytomegaloviruses in vitro. Consequently, animal cytomegaloviruses can be used as model systems for studying the pathogenesis, immunobiology, and molecular biology of cytomegalovirus-host and cytomegalovirus-cell interactions.
Staczek, J
Radioautographic studies on radiosulfate incorporation in the digestive organs of mice.
The sulfate uptake and accumulation in mouse digestive organs were studied by light microscopic radioautography. Two litters of normal ddY mice 30 days after birth, each consisting of 3 animals, were studied. One litter of animals were sacrificed 30 min after the intraperitoneal injections with phosphate buffered Na2(35)SO4, and the other litter animals were sacrificed 12 hr after the injections. Then several digestive organs, the parotid gland, the submandibular gland, the sublingual gland, antrum and fundus of the stomach, the duodenum, the jejunum, the ileum, the caecum, the ascending colon and the descending colon were taken out. The tissues were fixed, dehydrated, embedded in epoxy resin, sectioned, picked up onto glass slides, coated with radioautographic emulsion by a dipping method. AFter the exposure, they were developed, stained with toluidine blue and analyzed by light microscopy. As the results, many silver grains were observed on serous cells of the salivary glands, mucosa and submucosa of the stomach, villous cells and crypt cells of the small intestines and whole mucosa of the large intestines at 30 min after the injection. Then at 12 hr after the injection silver grains were observed on mucous cells of the salivary glands, some of the stomach glands, and mucigen granules of goblet cells in the small intestines and the large intestines. The numbers of silver grains observed in respective organs at 30 min were less than those at 12 hr. From these results, it is concluded that glycoprotein synthesis was demonstrated in several digestive organs by radiosulfate incorporation. In the salivary glands the silver grains were more observed in serous cells at 30 min, while in mucous cells more at 12 hr than 30 min after the injection. In other organs the silver grains were more at 30 min than at 12 hr. These results show the time difference of glycoprotein synthesis in respective organs. PMID:10425551
Nagata, T; Morita, T; Kawahara, I
Iodine increases and predicts incidence of thyroiditis in NOD mice: Histopathological and ultrastructural study.
Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed. A potassium iodide intake of 0.2 mg/animal/day was administered via drinking water, in experimental groups of 60 and 90 days (EG60 and EG90). Distended rough endoplasmic reticulum, degenerated mitochondria, debris and amorphous spaces or 'ill-defined' spaces were observed with electron microscopy (EM). Lymphocyte infiltration was observed in the two groups and the time of exposure to iodine did not increase the appearance of lymphocyte infiltration but significantly associated with the development of necrosis. The results of the present study demonstrated that the NOD mouse is a feasible experimental model for thyroiditis induced by iodine administration and may represent an opportunity to analyze the steps and factors associated with genetic autoimmune thyroiditis. High doses of ingested iodine were observed to precdict and increase the incidence of the thyroiditis process. PMID:23408765
Vecchiatti, Stella Maria Pedrossian; Guzzo, Maria Luisa; Caldini, Elia Garcia; Bisi, Hélio; Longatto-Filho, Adhemar; Lin, Chin Jia
Iodine increases and predicts incidence of thyroiditis in NOD mice: Histopathological and ultrastructural study
Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed. A potassium iodide intake of 0.2 mg/animal/day was administered via drinking water, in experimental groups of 60 and 90 days (EG60 and EG90). Distended rough endoplasmic reticulum, degenerated mitochondria, debris and amorphous spaces or 'ill-defined' spaces were observed with electron microscopy (EM). Lymphocyte infiltration was observed in the two groups and the time of exposure to iodine did not increase the appearance of lymphocyte infiltration but significantly associated with the development of necrosis. The results of the present study demonstrated that the NOD mouse is a feasible experimental model for thyroiditis induced by iodine administration and may represent an opportunity to analyze the steps and factors associated with genetic autoimmune thyroiditis. High doses of ingested iodine were observed to precdict and increase the incidence of the thyroiditis process.
Intravital microscopy in BLT-humanized mice to study cellular dynamics in HIV infection.
Humanized mouse models have, over the past few years, seen dramatic improvements, including the colonization of both lymphoid and nonlymphoid tissues with all major immune cell lineages, the development of T cells with human major histocompatibility complex restriction, and the ability to mount functional adaptive immune responses to human pathogens, as documented in some instances. This has greatly increased the range of questions related to the biology of human immunodeficiency virus (HIV) infection that can be usefully addressed through experimental approaches utilizing small animal models. Among these approaches is in vivo imaging, and specifically multiphoton intravital microscopy (MP-IVM), which allows for the investigation of dynamic biological processes at cellular and subcellular resolution in the tissues of live animals. We have recently begun to use MP-IVM in lymph nodes of humanized mice in order to examine HIV infectious spread in vivo at the tissue and cellular level. Here, we provide a short perspective on the close link between the patterns of immune cell migration and the mechanisms of viral dissemination, and summarize the results of our initial studies. PMID:24151320
Murooka, Thomas T; Mempel, Thorsten R
A Bayesian methodology for scaling radiation studies from animals to man
This paper describes a Bayesian methodology for integrating studies in experimental animals and humans to obtain a risk estimate for a radionuclide for which no data or very limited human data are available. The method is quite general and is not limited to radiation studies. In fact, it was first developed for chemical toxicants. The methodology is illustrated using studies
W. DuMouchel; P. G. B. Gror
Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis
Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of a repair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them.
Graves, Dana T.; Kang, Jun; Andriankaja, Oelisoa; Wada, Keisuke; Rossa, Carlos
Minimally invasive surgery and oxidative stress response: what have we learned from animal studies?
Oxidative stress (OS) is an integral part of the surgical stress response. Minimally invasive surgery causes less trauma, and thus attenuated stress response is anticipated. However, the pneumoperitoneum or pneumoretroperitoneum is implicated in free radical production. This study reviewed available data on the impact of minimally invasive surgery on OS response of animal models in a systematic way. Databases were searched up to and including January 2010. Most of the studies investigated the effect of pneumoperitoneum on OS, 3 studies investigated the effect of pneumoretroperitoneum on OS. There was a great heterogeneity on experimental conditions including animal models, measured OS markers, methods, and time periods of measurement. Published animal data do not allow a reliable conclusion on the effect of minimally invasive surgery on OS because of the great heterogeneity of experimental conditions. Besides, most studies focus on the effect of pneumoperitoneum, without taking into consideration the effect of less surgical trauma. PMID:23386145
Yiannakopoulou, Eugenia; Nikiteas, Nikolaos; Perrea, Despina; Tsigris, Christos
Health Benefits of Animal Research: The Mouse in Biomedical Research.
ERIC Educational Resources Information Center
Traces the history of using mice for medical research and discusses the benefits of using these animals for studies in bacteriology, virology, genetics (considering X-linked genetic homologies between mice and humans), molecular biology, immunology, hematology, immune response disorders, oncology, radiobiology, pharmacology, behavior genetics,…
Jonas, Albert M.
Toxicological Study and Efficacy of Blank and Paclitaxel-Loaded Lipid Nanocapsules After i.v. Administration in Mice
Purpose Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting entrapment of paclitaxel and increasing its antitumoural\\u000a effect in animal models after i.v. injection. The tolerance and efficacy of LNCs after repeated dose i.v. administration were assessed in mice. The maximum tolerated dose (MTD) and 50% lethal dose (LD50) were studied.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Paclitaxel-loaded LNC formulation was given i.v. at the dose of 12 mg\\/kg
José Hureaux; Frédéric Lagarce; Frédéric Gagnadoux; Marie-Christine Rousselet; Valérie Moal; Thierry Urban; Jean-Pierre Benoit
Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells
Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga)
Kulkarni, P.V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R.W.; Mathews, D.; Mason, R.P.; Oz, O.K. [Departments of Radiology and Pathology, University of Texas Southwestern Medical Center at Dallas, Texas 75390 (United States)
Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells
NASA Astrophysics Data System (ADS)
Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).
Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.
[Animal models for the study of systemic inflammatory response and parenteral nutrition].
The systemic inflammatory response syndrome (SRIS) seems to be due to the activation of the toll-like receptors, specific of the inflammatory response cells, through concrete cytosolic signals which lead to a cascade of reactions acting cytokins, growing factors and others inflammatory mediators. This kind of work revewes and discusses several classifications of animals models to study the SRIS, and propose to divide these models according to concrete goals, which can be the following ones: (1) To study innate and adaptative receptors of regulatory gens in the SRIS. (2) To study signals receptors (cytokines and growing factors). (3) To study the answer to signals. (4) To study treatments through specifics antinflammatory blockage. (5) Specific models of sepsis. (6) Others inducing models of SRIS. (7) Others therapeutical models. -Antinflammatories. -Antiacoagulans: Coagulations inhibition in human assays. Phase II Anticoagulans: Antitrombine III, PCA and TFPI. -Antibiotics. -Replacing Volume Treatments. -Surgical Treatments. As to the animals models to study Parenteral Nutrition, we could make the next classifications and sum it up: (1) Animal models to study the parenteral via of administration. (2) Models to study viability, absorption and local tolerance of the administration via. (3) Study models for complications. (4) Animal models to study pharmacodynamic, metabolization and to investigate the tolerance of new molecules or substrates. PMID:17416031
Morán Penco, J M
Studies on tumor incidence in mice exposed to GSM cell-phone radiation [Health Effects
This paper studies on tumor incidence in mice exposed to GSM cell-phone radiation. The first study of lymphomas in female Emu_Pim1 transgenic mice using frequencies and modulations specific to cellular mobile phones was conducted in Australia in which the incidence was shown to be significantly higher (odds ratio, OR = 2.4) in the exposed mice (43%) than in the sham
James C. Lin
Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases
Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n?=?2), experimental autoimmune encephalomyelitis (n?=?34), focal ischemia (n?=?16), intracerebral hemorrhage (n?=?61), Parkinson disease (n?=?45), and spinal cord injury (n?=?2). 112 meta-analyses (70%) found nominally (p?0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10?9). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature.
Sena, Emily S.; Aretouli, Eleni; Evangelou, Evangelos; Howells, David W.; Salman, Rustam Al-Shahi; Macleod, Malcolm R.; Ioannidis, John P. A.
Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.
Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. PMID:19025323
Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl
Harmonization of Animal Clinical Pathology Testing in Toxicity and Safety Studies
Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies
Kurt Weingand; Geoff Brown; Robert Hall; Dai Davies; Kent Gossett; Doug Neptun; Trevor Waner; Toshiaki Matsuzawa; Paul Salemink; Wilhelm Froelke; Jean-Pierre Provost; Gianni Dal Negro; John Batchelor; Mamoru Nomura; Horst Groetsch; Alphons Boink; Jon Kimball; David Woodman; Malcolm York; Eva Fabianson-Johnson; Michel Lupart; Elsa Melloni
Animal Technical Services- Bethesda
Only mice and rats from pathogen-free sources are allowed into NCI-managed animal facilities. NCI facilities in Bethesda are barrier facilities, which exclude helicobacter, as well as other known pathogens of laboratory mice and rats. The one exception is a conventional rodent facility in the ACRF Tower, where animal admission criteria based on known health status is more inclusive, but still subject to oversight and review by that facility's veterinarian.
Elaboration of laboratory strains of Ebola virus and study of pathophysiological reactions of animals inoculated with these strains
Selective passages in animals and cell cultures were used to produce a set of Ebola virus (EBO) laboratory strains with changed virulence for some animal genera. Comparative study of the genomes of wild-type EBO and selected variants formed the basis for studying the molecular causes of EBO virulence. Investigation of pathophysiological reactions of the animals inoculated with these strains allowed
A. A. Chepurnov; N. M. Zubavichene; A. A. Dadaeva
USC animal study finds fasting makes brain tumors more vulnerable to radiation therapy
A new study from USC researchers is the first to show that controlled fasting improves the effectiveness of radiation therapy in cancer treatments, extending life expectancy in mice with aggressive brain tumors. The latest study, published in PLOS One, is the first to show that periods of fasting appear to have an augmenting effect on radiation therapy in treating gliomas, the most commonly diagnosed brain tumor.
Inhalation studies of Mt. St. Helens volcanic ash in animals. III. Host defense mechanisms.
The effects of inhalation exposure of mice or rats to 9.4 mg/m3 volcanic ash, 2.5 mg/m3 SO2, or both on host defense mechanisms were assessed. Cytologic changes in pulmonary lavage fluid included an increase in percentage polymorphonuclear leukocytes due to SO2 exposure and an increase in eosinophils due to ash. SO2 and ash also produced decreases in percentage alveolar macrophages. In the case of ash-exposed animals, this decrease was offset by an increase in lymphocytes. Total cell counts and viability were not affected by any of the exposures. Pulmonary clearance mechanisms were affected in that there were both decreased alveolar macrophage phagocytic capability following ash and ash + SO2 exposures and depressed ciliary beat frequency attributable to ash exposure. None of the inhalation exposures caused increases in susceptibility to an immediate or 24 hr postexposure aerosol challenge with Streptococcus. However, intratracheal instillation of both fine- and coarse-mode volcanic ash caused slight but significant increases in mortality due to bacterial challenge 24 hr after the instillation. The phytohemagglutinin-induced blastogenic response of splenic lymphocytes from exposed animals did not differ significantly from that of control lymphocytes, although the lipopolysaccharide-induced blastogenic response was enhanced. Ash exposure had no effect on susceptibility to murine cytomegalovirus. In summary, volcanic ash alone or in combination with SO2 had only minimal effects on certain host defense mechanisms. PMID:3996344
Grose, E C; Grady, M A; Illing, J W; Daniels, M J; Selgrade, M K; Hatch, G E
Animal models for the study of hepatitis C virus infection and replication
Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.
MacArthur, Kristin L; Wu, Catherine H; Wu, George Y
Practical method for radioactivity distribution analysis in small-animal PET cancer studies
We present a practical method for radioactivity distribution analysis in small-animal tumors and organs using positron emission tomography imaging with a calibrated source of known activity and size in the field of view. We reconstruct the imaged mouse together with a source under the same conditions, using an iterative method, Maximum Likelihood Expectation-Maximization with System Modeling, capable of delivering high resolution images. Corrections for the ratios of geometrical efficiencies, radioisotope decay in time and photon attenuation are included in the algorithm. We demonstrate reconstruction results for the amount of radioactivity within the scanned mouse in a sample study of osteolytic and osteoblastic bone metastasis from prostate cancer xenografts. Data acquisition was performed on the small-animal PET system which was tested with different radioactive sources, phantoms and animals to achieve high sensitivity and spatial resolution. Our method uses high resolution images to determine the volume of organ or tumor and the amount of their radioactivity, has the possibility of saving time, effort and the necessity to sacrifice animals. This method has utility for prognosis and quantitative analysis in small-animal cancer studies, and will enhance the assessment of characteristics of tumor growth, identifying metastases, and potentially determining the effectiveness of cancer treatment. The possible application for this technique could be useful for the organ radioactivity dosimetry studies.
Slavine, Nikolai V.; Antich, Peter P.
Inhalation studies of Mt. St. Helens volcanic ash in animals *1I. Introduction and exposure system
Due to the lack of information on the effects of inhaled Mt. St. Helens volcanic ash and its potential interaction with sulfur dioxide (SOâ), animal studies were performed to determine the acute and chronic health effects of a short-term exposure. This paper describes the inhalation exposure system designed for these studies and theoretically compares the pulmonary deposition in the rats
J. A. Graham; F. J. Miller; D. W. Davies; M. E. Hiteshew; L. C. Walsh
The review is organized into two major sections: Part I, a clinical review which will examine only those studies relevant to the issue of behavioral effects resulting from relatively low-level chronic exposure, and Part II, a review of animal studies which will focus on behaviora...
WWW design code – a new tool for colour estimation in animal studies
BACKGROUND: The colour of animals' skin, fur, feathers or cuticula has been estimated in a large number of studies. The methods used to do so are diverse, with some being costly and not available to all researchers. In a study to measure plumage colour in a bird species, a new method of creating a colour chart was developed. While colour-charts
Ĺsa Berggren; Juha Merilä
Animal Algorithm Animation Tool
NSDL National Science Digital Library
Guido RöĂÂling, who works for the Rechnerbetriebsgruppe (Computer Support Center) of the Department of Computer Science at the Darmstadt University of Technology, has created this website about ANIMAL. ANIMAL is a general-purpose animation tool with a current focus on algorithm animation. Posted on this website are the animations, including screenshots, classification and description, a user guide, other instructions, and research papers. A section with examples provides an overview and screen shots of the animations, such as one that shows how LZW compression (an algorithm created in 1984 by Lempel, Ziv and Welch) works.
A tale of mice and (wo)men: development of and insights from an "all human" animal model of breast cancer metastasis to bone.
There are 200,000 new cases of breast cancer (BrCa) annually in the United States. Metastasis to bone signals a life-threatening phase of this disease. Little progress has been made in understanding the pathogenesis of metastasis. Few validated drug targets have been identified. So there is a compelling need to understand the molecular mechanisms by which BrCa metastasizes to bone (osteotropism). There is need for animal models that reflect the complex biology of metastasis in humans. We performed research designed to elucidate the mechanisms of osteotropism from both sides of the tumor-stroma interface. We created an "all human" model in which human bone is transplanted into non-obese diabetic/severe combined immunodeficient immunodeficient (NOD/SCID) mice. Human BrCa cells injected into the mammary fat pad later metastasize to bone. We also found traffic in the opposite direction: bone marrow stem cells migrate from human bone to human breast tumors in the mouse. We are identifying osteotropism genes used by BrCa to metastasize to human bone. PMID:23303981
Rosenblatt, Michael
Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis
Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model.
Kalmar, Isabelle; Vanrompay, Daisy
Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice
Background Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. Methodology ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. Principal Findings After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4–8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. Conclusions The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast.
Boll, Hanne; Nittka, Stefanie; Doyon, Fabian; Neumaier, Michael; Marx, Alexander; Kramer, Martin; Groden, Christoph; Brockmann, Marc A.
[Calcium blockers in the therapy of vertebrobasilar insufficiency. Results of animal experiments and clinical studies].
Vertebrobasilar insufficiency (VBI) is a clinical syndrome which includes different transient brain stem symptoms. In addition to anamnesis and clinical study electronystagmography (ENG) is regarded as the most important method for testing the labyrinthine and brain stem system. Typical findings, not only in patients with VBI, but also in animal experiments (occlusion of one vertebral artery) are an increase in nystagmus frequency and decrease in nystagmus amplitude. The present study concerns two calcium antagonists: flunarizine and nimodipine. During tests on patients the caloric and the rotatory nystagmus and during animal experiments the rotatory nystagmus was investigated. Patient tests as well as animal experiments showed, that flunarizine and nimodipine have a depressant influence on the pathologically increased nystagmus frequency. With both substances there was also a trend to normalization of nystagmus amplitude as well as an improvement of clinical symptoms. PMID:6383990
Hofferberth, B
Having an almost unlimited capacity to regenerate tissues lost to age and injury, planarians have long fascinated naturalists. In the Western hemisphere alone, their documented history spans more than 200 years. Planarians were described in the early 19th century as being "immortal under the edge of the knife," and initial investigation of these remarkable animals was significantly influenced by studies of regeneration in other organisms and from the flourishing field of experimental embryology in the late 19th and early 20th centuries. This review strives to place the study of planarian regeneration into a broader historical context by focusing on the significance and evolution of knowledge in this field. It also synthesizes our current molecular understanding of the mechanisms of planarian regeneration uncovered since this animal's relatively recent entrance into the molecular-genetic age.
Elliott, Sarah A.; Sanchez Alvarado, Alejandro
Treatment of Alport syndrome: beyond animal models
Alport syndrome (AS) is a hereditary glomerulopathy due to abnormal composition of the glomerular basement membrane, leading to end-stage renal disease (ESRD). Studies of animal models of AS have suggested a variety of potentially effective therapies, but none of these has been definitely shown to prevent or delay ESRD in human AS. Studies in Alport mice suggest that angiotensin inhibition
Oliver Gross; Clifford E Kashtan
Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model
Abstract To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established.
Cai, Wei-Xin; Zheng, Li-Wu; Weber, Franz E.; Li, Chun-Lei; Ma, Li; Ehrbar, Martin
Cage-change interval preference in mice.
Before animal research facilities began using individually ventilated cage (IVC) systems for mice, cages were often changed one or more times per week. When using IVC systems, however, it is standard practice to change cages only once every 2-3 weeks. When deciding how often to change cages, personnel may consider the cost of labor needed to change the cage, as well as the cage type and bedding type, rather than animal preference or concern for animal well-being. The authors carried out a simple preference test in groups of mice. Mice were allowed to choose between an unsoiled cage and cages that had not been changed for 1 d, 7 d or 14 d. When evaluating where mice positioned their nests and the amount of time mice spent in the various cages, the authors found that the mice preferred the unsoiled cage. Younger mice (<150 d old) showed a stronger preference for the unsoiled cage than did older mice (>150 d old). Further studies are warranted to evaluate mice's preferences for cages changed at different intervals and to determine whether prolonging the interval between cage changes has any negative effects on mice. PMID:21691297
Godbey, Tamara; Gray, Gordon; Jeffery, Dean
Animal Models of C-Reactive Protein
As the main theme of this special issue, CRP not only is an inflammatory marker but also has diverse biological functions associated with different diseases. To investigate CRP's physiologies and their relationship with human pathological significance, it is essential to use appropriate animal models for translational research. The most popular models for the study of CRP are transgenic mice. However, researchers should be careful when extrapolating the findings derived from these animal models. This review will discuss the current concerns on CRP transgenic mice and rabbits.
Torzewski, Michael; Waqar, Ahmed Bilal; Fan, Jianglin
Toxicology studies of a chemical mixture of 25 groundwater contaminants. II. Immunosuppression in B6C3F1 mice
Concern over the potential adverse health effects of chemically contaminated groundwater has existed for many years. In general, these studies have focused on retrospective epidemiological studies for cancer risk. In the present studies, immune function was monitored in female B6C3F1 mice exposed to a chemical mixture in drinking water for either 14 or 90 days. The mixture consisted of 25 common groundwater contaminants frequently found near toxic waste dumps, as determined by EPA surveys. None of the animals developed overt signs of toxicity such as body or liver weight changes. Mice exposed to the highest dose of this mixture for 14 or 90 days showed immune function changes which could be related to rapidly proliferating cells, including suppression of hematopoietic stem cells and of antigen-induced antibody-forming cells. Some of these responses, e.g., granulocyte-macrophage colony formation, were also suppressed at lower concentrations of the chemical mixture. There were no effects on T cell function or T and B cell numbers in any of the treatment groups. Altered resistance to challenge with an infectious agent also occurred in mice given the highest concentration, which correlated with the immune function changes. Paired-water studies indicated that the immune effects were related to chemical exposure and not to decreased water intake. These results suggest that long-term exposure to contaminated groundwater may represent a risk to the immune system in humans.
Germolec, D.R.; Yang, R.S.; Ackermann, M.F.; Rosenthal, G.J.; Boorman, G.A.; Blair, P.; Luster, M.I. (National Institutes of Environmental Health Sciences, Research Triangle Park, NC (USA))
Green fluorescent protein-transgenic mice: immune functions and their application to studies of lymphocyte development
Green fluorescent protein (GFP) transgenic (GFP+) mice express GFP in most tissues except erythrocytes and hair. Immune responses of GFP+ mouse and their application to studies of lymphocyte development were investigated. Flow cytometric analyses revealed that differentiation patterns of lymphocytes from GFP+ mice are equivalent to those from parental C57BL\\/6 mice. There was no difference in mature T-cell proliferative ability
Naoto Kawakami; Naoki Sakane; Fumiko Nishizawa; Mutsumi Iwao; So-ichiro Fukada; Kazutake Tsujikawa; Yasuhiro Kohama; Masahito Ikawa; Masaru Okabe; Hiroshi Yamamoto
Genotypic and Phenotypic Studies of Murine Intestinal Lactobacilli: Species Differences in Mice with and without Colitis
Lactobacilli represent components of the commensal mammalian gastrointestinal microbiota and are useful as probiotics, functional foods, and dairy products. This study includes systematic polyphasic analyses of murine intestinal Lactobacillus isolates and correlation of taxonomic findings with data from cytokine produc- tion assays. Lactobacilli were recovered from mice with microbiota-dependent colitis (interleukin-10 (IL-10)- deficient C57BL\\/6 mice) and from mice without colitis
J. A. Pena; S. Y. Li; P. H. Wilson; S. A. Thibodeau; A. J. Szary; J. Versalovic
Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats.
Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH. PMID:19011597
Sonabend, A M; Ulasov, I V; Han, Y; Rolle, C E; Nandi, S; Cao, D; Tyler, M A; Lesniak, M S
Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models
Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [?-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) ?g/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (? = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.
[(11)C-carbonyl]CEP-32496: Radiosynthesis, biodistribution and PET study of brain uptake in P-gp/BCRP knockout mice.
CEP-32496 is a novel, orally active serine/threonine-protein kinase B-raf (BRAF) (V600E) kinase inhibitor that is being investigated in clinical trials for the treatment of some cancers in patients. In this study, we developed [(11)C-carbonyl]CEP-32496 as a novel positron emission tomography (PET) probe to study its biodistribution in the whole bodies of mice. [(11)C]CEP-32496 was synthesized by the reaction of 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine hydrochloride (1·HCl) with [(11)C]phosgene, followed by treatment with 3-(6,7-dimethoxyquinozolin-4-yloxy)aniline (2). Small-animal PET studies with [(11)C]CEP-32496 indicated that radioactivity levels (AUC0-90min, SUV×min) accumulated in the brains of P-gp/BCRP knockout mice at a 8-fold higher rate than in the brains of wild-type mice. PMID:24930831
Shimoda, Yoko; Yui, Joji; Fujinaga, Masayuki; Xie, Lin; Kumata, Katsushi; Ogawa, Masanao; Yamasaki, Tomoteru; Hatori, Akiko; Kawamura, Kazunori; Zhang, Ming-Rong
NSDL National Science Digital Library
The public debate on animal research sometimes gets so heated that the facts can be overlooked. How many animals are used in research every year? Do people know that most of them are mice or rats? Why are animals genetically modified? How is animal research regulated? How are the animals cared for? What actually happens to research animals? How does the use of animals in research and testing compare with other uses of animals by society? This website aims to answer all of these questions as well as provide information on animal research and human health, policy issues, and latest news. This website also includes a learning center. Information is geared towards learners in the U.K.
Understanding Animal Research (Understanding Animal Research)
In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals.
This in vivo study confirmed impaired hemostasis during hypothermia in a swine model. Group I (normothermic, n = 8) and group II (hypothermic, n = 8) animals were anesthetized and instrumented for continuous peritoneal irrigation and monitoring of heart rate and blood pressure. The effects of hypothermia, hypotension, and inotrope on bleeding time and bleeding from two types of arterial injuries were evaluated. Our findings were that (1) bleeding time was significantly prolonged in hypothermic animals; (2) the differences in blood loss from partially torn artery (PTA) and completely cut artery (CCA) at both normothermic and hypothermic temperatures did not reach statistical significance; and (3) blood loss from PTA was greater than CCA when norepinephrine (Levophed) was infused to elevate blood pressure in hypotensive animals at normal core temperature. PMID:8355304
Oung, C M; Li, M S; Shum-Tim, D; Chiu, R C; Hinchey, E J
Short Animation Movies as Advance Organizers in Physics Teaching: A Preliminary Study
ERIC Educational Resources Information Center
Background: Advance organizers are instructional materials that help students use previous knowledge to make links with new information. Short animation movies are a possible format and are well suited for physics, as they can portray dynamic phenomena and represent abstract concepts. Purpose: The study aimed to determine guidelines for the…
Koscianski, Andre; Ribeiro, Rafael Joao; da Silva, Sani Carvalho Rutz
Evaluation of Drosophila melanogaster as an alternative animal for studying the neurotoxicity of heavy metals
Heavy metals cause irreversible neurobehavioral damage in many developing mammals, but the mechanisms of this damage are unknown. The influence of three heavy metal compounds, triethyllead chloride, lead acetate and cadmium chloride, on lethality, development, behavior and learning was studied using the fruit fly,Drosophila melanogaster. This animal was used because it allows hundreds of subjects to be assayed very easily
Jonathan M. Akins; Joyce A. Schroeder; Danny L. Browert; H. Vasken Aposhian
The use of computer animation of mapped cardiac potentials in studying electrical conduction properties of arrhythmias
It is shown how computer animation of potentials recorded from 121 electrodes on the canine heart surface is used to study the electrical conduction properties of the heart. Color indicates the magnitude of each electrode's recorded voltage on the workstation screen. As each electrode's recorded voltage changes over time the corresponding color on the screen changes. The colors for all
Cary Laxer; C. A. Alferness; William M. Smith; R. E. Ideker
A Multi-Year Field Olfactometry Study Near a Concentrated Animal Feeding Operation
This study developed and tested a protocol for monitoring odors near a Concentrated Animal Feeding Operation (CAFO). The Nasal Ranger, a portable field olfactometry instrument, was used by a panel of trained individuals to conduct the monitoring near a swine CAFO. Monitors were selected based on olfactory sensitivity, scheduling availability, and lack of association with the CAFO or residential neighbors
Pamela Dalton; Edward A. Caraway; Herman Gibb; Keri Fulcher
Animal Model Study of Reproductive Toxicity of the Chronic Exposure of Dicofol
Dicofol is an organochlorine acaricide widely used in local market. The present study was conducted to evaluate the dicofol chronic toxicity of male fertility indices and reproductive toxicity resulted from acaricide through sexual and reproductive hormones as well as investigate the effect on testicular function and epididymal oxidative parameters I a animal model. In this investigation, two equal groups of
Afaf A. El-Kashoury; Afrah F. Salama; Adel I. Selim; Rania A. Mohamed
Morphological studies on larval and adult Echinococcus granutosus of buffalo, cattle, sheep, goats and camel origin revealed non-significant difference as regards the total number of hooks as well as shape and arrangement of the hooks. The mean total length of large and small hooks did not vary significantly in protoscoleces from different animal origin but mean total length of large
The Relationship between Domestic Violence and Animal Abuse: An Australian Study
ERIC Educational Resources Information Center
Several North American studies have found a connection between domestic violence and animal abuse. This article reports on the first Australian research to examine this connection. A group of 102 women recruited through 24 domestic violence services in the state of Victoria and a nondomestic violence comparison group (102 women) recruited from the…
Volant, Anne M.; Johnson, Judy A.; Gullone, Eleonora; Coleman, Grahame J.
A Study of Firesetting and Animal Cruelty in Children: Family Influences and Adolescent Outcomes.
ERIC Educational Resources Information Center
Objective: To investigate relationships among family risk factors, childhood firesetting and animal cruelty, and adolescent delinquency. Method: In 1990, mothers and children participating in a 10-year prospective study provided information about family risk factors and childhood problem behavior. Subsequent interviews with 86% of the sample in…
Becker, Kimberly D.; Stuewig, Jeffrey; Herrera, Veronica M.; McCloskey, Laura A.
Chemical and pharmacological studies of Phyllanthus caroliniensis in mice.
The aim of this study was to isolate and characterize the constituents of the hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis, and also to evaluate the preliminary antinociceptive action of the HE and purified compounds in mice. Phytosterols, quercetin, gallic acid ethyl ester and geraniin were identified in P. caroliniensis on the basis of 1H and 13C NMR spectral data and by mixed co-TLC and co-HPLC injection with authentic samples. The HE of P. caroliniensis (10-100 mg kg-1, i.p.) inhibited, in a dose-related manner, acetic acid-induced abdominal constrictions in mice, with a mean ID50 value of 23.7 mg kg-1. In the formalin test, the HE given intraperitoneally (1-30 mg kg-1) or orally (25-600 mg kg-1) caused graded inhibitions of both the neurogenic (first phase) and the inflammatory response (late phase) of formalin-induced licking. The HE was 54-fold more effective in inhibiting the late phase than it was in inhibiting the first phase of the formalin test, with mean ID50 values of 3.6 and 196.4 mg kg-1, respectively. The HE failed, however, to affect the oedematogenic response associated with the late phase of formalin-induced pain. In addition, the reference drug, aspirin, given intraperitoneally (1-100 mg kg-1) or orally (100-600 mg kg-1), caused significant inhibition of the late but not the first phase of the formalin test. Pharmacological analysis also revealed that quercetin, gallic acid ethyl ester and a semi-purified fraction of flavonoids (1-100 mg kg-1, i.p.) exhibited graded and significant antinociception against acetic acid-induced abdominal constriction. The mean ID50 values (mg kg-1) for these effects were: 18.8, 34.7 and 5.3, respectively. It is concluded that quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might account for the antinociceptive action reported for the HE of P. caroliniensis. PMID:9004183
Cechinel Filho, V; Santos, A R; De Campos, R O; Miguel, O G; Yunes, R A; Ferrari, F; Messana, I; Calixto, J B
Study on the Mechanical Instability of MICE Coupling Magnets
The superconducting coupling solenoid magnet is one of the key equipment in the Muon Ionization Cooling Experiment (MICE). The coil has an inner radius of 750 mm, length of 281 mm and thickness of 104 mm at room temperature. The peak induction in the coil is about 7.3 T with a full current of 210 A. The mechanical disturbances which might cause the instability of the impregnated superconducting magnet involve the frictional motion between conductors and the cracking of impregnated materials. In this paper, the mechanical instability of the superconducting coupling magnet was studied. This paper presents the numerical calculation results of the minimum quench energy (MQE) of the coupling magnet, as well as the dissipated strain energy in the stress concentration region when the epoxy cracks and the frictional energy caused by 'stick-slip' of the conductor based on the bending theory of beam happens. Slip planes are used in the coupling coil and the frictional energy due to 'slow slip' at the interface of the slip planes was also investigated. The dissipated energy was compared with MQE, and the results show that the cracking of epoxy resin in the region of shear stress concentration is the main factor for premature quench of the coil.
Wang, Li; Pan, Heng; Gou, Xing Long; Wu, Hong; Zheng, Shi Xian; Green, Michael A
The Effects of Dairy Components on Energy Partitioning and Metabolic Risk in Mice: A Microarray Study
Background\\/Aim: High-calcium diets modulate energy metabolism and suppress inflammatory stress. These effects are primarily mediated by calcium suppression of calcitriol. We have now investigated the effect of additional components in dairy products [branched-chain amino acids (BCAA) and angiotensin-converting enzyme inhibitors (ACEi)] on adipocyte and muscle metabolism in an animal model of diet-induced obesity. Methods: aP2-agouti mice were fed four different
Antje Bruckbauer; Julia Gouffon; Bhanu Rekapalli; Michael B. Zemel
An XRF study of trace elements accumulation in kidneys of tumor-bearing mice after treatment with cis DDP with and without selenite and selenocistamine
The effect ofcis-DDP treatment with and without selenite and selenocistamine was studied on kidneys of tumor-bearing mice. The amounts ofcis-DDP, selenite, and selenocistamine injected were chosen so as to be compatible with the treatment of humans. The animals\\u000a were sacrificed at 7, 14, and 28 d after treatment. The kidneys were removed and subjected to trace element analysis by a
Cesia Shenberg; Miriam Boazi; Jacob Cohen; Abraham Klein; Marcus Kojler; Abraham Nyska
Clinical perspectives for the study of craving and relapse in animal models.
Several major clinical models of alcoholism in which craving plays a role are summarized and key questions are raised regarding the course of craving in the emergence of alcoholism, how it varies in different stages of the disorder (e.g. active alcoholic, withdrawal, protracted abstinence) and what craving may contribute to major signs and symptoms of alcoholism. Turning to animal models, a plea is made for development of a standardized definition of human craving that can be represented and operationalized in animal models. Until there is scientific consensus on such a definition, four ways are elucidated in which animal model research can contribute to advances in our knowledge of human craving and the role it plays in addictive behavior: (1) engaging both basic and clinical researchers to identify parallel constructs of craving and predictors of craving for adoption in comparative human and animal model studies; (2) conducting exploratory research on craving in animal models using relapse to drinking as the dependent measure; (3) identifying mechanisms that underlie clinical signs and symptoms of alcoholism in animal models; and (4) identifying genetic models in basic research that account for variations in response to alcohol that may also occur in humans. This latter point is made in a discussion of the genetic contribution to voluntary alcohol consumption, the alcohol deprivation effect, tolerance and dependence, as illustrated by differences between alcohol-preferring (P) rats and -nonpreferring (NP) rats. The review concludes with four questions and issues that need to be among those that guide future research on craving. PMID:11002902
Li, T K
Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.
The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(?M51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors). PMID:20808290
Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A
The usefulness of severe combined immunodeficiency (SCID) mice to study human carcinogenesis
In the present study, we engrafted normal colonic epithelia and histologically diagnosed colonic adenomas from a familial adenomatous polyposis (FAP) patient into severe combined immunodeficient (SCID) mice and subsequently examined them histologically and molecular biologically. Successful engraftment and metastasis was observed. The facts that human normal colonic epithelium and adenomatous polyps can take in SCID mice indicates the possibility that
Takashi Ito; Toshio Seyama; Seishi Kyoizumi; Seigo Teraoka; Keisuke S. Iwamoto; Terumi Mizuno; Naohiro Tsuyama; Toshimasa Asahara; Kiyohiko Dohi; Mitoshi Akiyama
Cytogenetic studies in mice treated with the jet fuels, Jet-A and JP-8 Abstract The genotoxic potential of the jet fuels, Jet-A and JP-8, were examined in mice treated on the skin with a single dose of 240 ug/mouse. Peripheral blood smears were prepared at the start of the ...
Preliminary Studies on the Antinociceptive Activity of Vaccinium ashei Berry in Experimental Animal Models
Abstract The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2–6.4?mg/kg/day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10?mg/kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.
Ramirez, Maria Rosana; Guterres, Leandra; Dickel, Odila E.; de Castro, Micheli R.; Henriques, Amelia T.; de Souza, Marcia M.
Measurement of the toughness of bone: A tutorial with special reference to small animal studies?
Quantitative assessment of the strength and toughness of bone has become an integral part of many biological and bioengineering studies on the structural properties of bone and their degradation due to aging, disease and therapeutic treatment. Whereas the biomechanical techniques for characterizing bone strength are well documented, few studies have focused on the theory, methodology, and various experimental procedures for evaluating the fracture toughness of bone, i.e., its resistance to fracture, with particular reference to whole bone testing in small animal studies. In this tutorial, we consider the many techniques for evaluating toughness and assess their specific relevance and application to the mechanical testing of small animal bones. Parallel experimental studies on wild-type rat and mouse femurs are used to evaluate the utility of these techniques and specifically to determine the coefficient of variation of the measured toughness values.
Ritchie, R.O.; Koester, K.J.; Ionova, S.; Yao, W.; Lane, N.E.; Ager, J.W.
Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals.
The purpose of this work was to improve of the spatial resolution of a whole-body positron emission tomography (PET) system for experimental studies of small animals by incorporation of scanner characteristics into the process of iterative image reconstruction. The image-forming characteristics of the PET camera were characterized by a spatially variant line-spread function (LSF), which was determined from 49 activated copper-64 line sources positioned over a field of view (FOV) of 21.0 cm. This information was used to model the image degradation process. During the course of iterative image reconstruction, the forward projection of the estimated image was blurred with the LSF at each iteration step before the estimated projections were compared with the measured projections. The imaging characteristics of the high-resolution algorithm were investigated in phantom experiments. Moreover, imaging studies of a rat and two nude mice were performed to evaluate the imaging properties of our approach in vivo. The spatial resolution of the scanner perpendicular to the direction of projection could be approximated by a one-dimensional Gaussian-shaped LSF with a full-width at half-maximum increasing from 6.5 mm at the centre to 6.7 mm at a radial distance of 10.5 cm. The incorporation of this blurring kernel into the iteration formula resulted in a significantly improved spatial resolution of about 3.9 mm over the examined FOV. As demonstrated by the phantom and the animal experiments, the high-resolution algorithm not only led to a better contrast resolution in the reconstructed emission scans but also improved the accuracy for quantitating activity concentrations in small tissue structures without leading to an amplification of image noise or image mottle. The presented data-handling strategy incorporates the image restoration step directly into the process of algebraic image reconstruction and obviates the need for ill-conditioned "deconvolution" procedures to be performed on the projections or on the reconstructed image. In our experience, the proposed algorithm is of special interest in experimental studies of small animals. PMID:9211765
Brix, G; Doll, J; Bellemann, M E; Trojan, H; Haberkorn, U; Schmidlin, P; Ostertag, H
Development of a high-sensitivity BGO well counter for small animal PET studies.
In quantitative measurements of small animal PET studies, blood sampling is limited due to the small amounts of blood such animals can provide. In addition, injection doses are quite limited. In this situation, a high-sensitivity well counter would be useful for reducing the amount of the blood sample needed from small animals. Bismuth germinate (BGO) has a high stopping power for high-energy gamma rays compared to NaI(Tl), which is commonly used for conventional well counters. We have developed a BGO well counter and have tested it for blood-sampling measurements in small animals. The BGO well counter uses a square BGO block (59 × 59 × 50 mm) with a square open space (27 × 27 × 34 mm) in the center of the block. The BGO block was optically coupled to a 59-mm square-shaped photomultiplier tube (PMT). Signals from the PMT were digitally processed for the integration and energy window setting. The results showed that the energy spectrum of the BGO well counter measured with a Na-22 point source provided counts that were about 6 times higher for a 1022-keV (511 keV × 2) gamma peak than the spectrum of a 2-in. NaI(Tl) well counter. The relative sensitivity of the developed BGO well counter was 3.4 times higher than that of a NaI(Tl) well counter. The time activity curve of arterial blood was obtained successfully with the BGO well counter for a F-18-FDG study on rat. The BGO well counter will contribute to reducing the amount of sampled blood and to improving the throughput of quantitative measurements in small animal PET studies. PMID:21987349
Yamamoto, Seiichi; Watabe, Hiroshi; Kanai, Yasukazu; Watabe, Tadashi; Imaizumi, Masao; Shimosegawa, Eku; Hatazawa, Jun
In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study
The neurotensin receptor (NTS1) has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET) using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The 177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals). Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [68Ga]DOTA-RGD. At days 7–10 after treatment with four fractionated doses of 11–14 MBq (each at days 0, 3, 6 and 10), the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy.
Maschauer, Simone; Ruckdeschel, Tina; Tripal, Philipp; Haubner, Roland; Einsiedel, Jurgen; Hubner, Harald; Gmeiner, Peter; Kuwert, Torsten; Prante, Olaf
Intravital microscopy: a novel tool to study cell biology in living animals
Intravital microscopy encompasses various optical microscopy techniques aimed at visualizing biological processes in live\\u000a animals. In the last decade, the development of non-linear optical microscopy resulted in an enormous increase of in vivo\\u000a studies, which have addressed key biological questions in fields such as neurobiology, immunology and tumor biology. Recently,\\u000a few studies have shown that subcellular processes can be imaged
Roberto Weigert; Monika Sramkova; Laura Parente; Panomwat Amornphimoltham; Andrius Masedunskas
Effect of Tranquilizers on Animal Resistance to the Adequate Stimuli of the Vestubular Apparatus.
National Technical Information Service (NTIS)
The effect of tranquilizers on vestibulospinal reflexes and motor activity was studied in 900 centrifuged albino mice. Actometric studies have shown that the tranquilizers have a group capacity for increasing animal resistance to the action of adequate st...
Y. B. Maksimovich N. V. Khinchikashvili
[Light and scanning electron studies on the morphology of the vaginal plug in laboratory animals].
Serial sections of vaginal plugs of mice, rats, guinea pigs and hamsters (Cricetulus griseus) were studied by light microscopy as well as whole plugs and freeze-fractures by scanning electron microscopy. The vaginal plugs are encircled by a layer of superficial cells of the vaginal epithelium and consist of coagulated seminal fluid, containing irregular holes. The spermatoza are mainly localized inside bigger cavities. Scanning electron microscopic study of freeze-fractured plugs reveals, that this method gives useful information about the inner structure of spermatozoa tails. PMID:6893258
Rosenbauer, K A; Campean, N; Campean, C
Assessment of GE food safety using '-omics' techniques and long-term animal feeding studies.
Despite the fact that a thorough, lengthy and costly evaluation of genetically engineered (GE) crop plants (including compositional analysis and toxicological tests) is imposed before marketing some European citizens remain sceptical of the safety of GE food and feed. In this context, are additional tests necessary? If so, what can we learn from them? To address these questions, we examined data from 60 recent high-throughput '-omics' comparisons between GE and non-GE crop lines and 17 recent long-term animal feeding studies (longer than the classical 90-day subchronic toxicological tests), as well as 16 multigenerational studies on animals. The '-omics' comparisons revealed that the genetic modification has less impact on plant gene expression and composition than that of conventional plant breeding. Moreover, environmental factors (such as field location, sampling time, or agricultural practices) have a greater impact than transgenesis. None of these '-omics' profiling studies has raised new safety concerns about GE varieties; neither did the long-term and multigenerational studies on animals. Therefore, there is no need to perform such long-term studies in a case-by-case approach, unless reasonable doubt still exists after conducting a 90-day feeding test. In addition, plant compositional analysis and '-omics' profiling do not indicate that toxicological tests should be mandatory. We discuss what complementary fundamental studies should be performed and how to choose the most efficient experimental design to assess risks associated with new GE traits. The possible need to update the current regulatory framework is discussed. PMID:23253614
Ricroch, Agnčs E
Animal Science Experts' Opinions on the Non-Technical Skills Secondary Agricultural Education Graduates Need for Employment in the Animal Science Industry: A Delphi Study
ERIC Educational Resources Information Center
Non-technical, employability skills are in high demand for entry-level job-seekers. As such, this study sought to describe the perceptions of Oklahoma's animal science industry leaders as it related to the employability skills needed for entry-level employment of high school graduates who had completed coursework in Oklahoma's Agricultural, Food…
Slusher, Wendy L.; Robinson, J. Shane; Edwards, M. Craig
Interleukin-6 reduces cartilage destruction during experimental arthritis. A study in interleukin-6-deficient mice.
Using interleukin (IL)-6-deficient (IL-6(0/0) mice or wild-type mice, we investigated the controversial role of IL-6 in joint inflammation and cartilage pathology during zymosan-induced arthritis (ZIA). Monoarticular arthritis was elicited by injection of zymosan into the right knee joint cavity. Production of IL-1, tumor necrosis factor (TNF), IL-6, and nitric oxide by the inflamed knee was assessed in washouts of joint capsule specimens. Plasma corticosterone was measured using a radioimmunoassay. Proteoglycan synthesis was assessed using [35S]sulfate incorporation into patellas ex vivo. Joint swelling was quantified by joint uptake of circulating 99mTechnetium pertechnetate. Histology was taken to evaluate cellular infiltration and cartilage damage. Zymosan caused a rapid increase in articular IL-1, IL-6, TNF, and NO levels. Except for IL-6, the released amounts and time course of these mediators were comparable in the IL-6-deficient mice and the wild-type mice. Elevated plasma corticosterone levels were measured during the first day of arthritis in both strains. At day 2 of ZIA, joint inflammation (joint swelling and cell exudate) in IL-6-deficient mice was comparable with that in the wild-type mice. The marked suppression of chondrocyte proteoglycan synthesis and proteoglycan degradation were on the average higher in the IL-6-deficient mice. Together this resulted in a more pronounced proteoglycan depletion in the IL-6-deficient mice as compared with the wild-type mice during the first week of arthritis. Injection of recombinant IL-6 into the joint cavity corrected the IL-6 deficiency and significantly reduced cartilage destruction. Inflammation was more chronic in the wild-type mice, and these mice also showed a higher prevalence for osteophyte formation. In ZIA, IL-6 plays a dual role in connective tissue pathology, reducing proteoglycan loss in the acute phase and enhancing osteophyte formation in the chronic phase. The latter could be related to the more severe joint inflammation as seen in the normal (IL-6-producing) animals during the chronic phase of arthritis. Images Figure 2 Figure 2
van de Loo, F. A.; Kuiper, S.; van Enckevort, F. H.; Arntz, O. J.; van den Berg, W. B.
Dominant lethal studies with the halogenated olefins vinyl chloride and vinylidene dichloride in male CD-1 mice
The mutagenic activity of vinyl chloride (VC) and vinylidene dichloride (VDC) at three exposure levels was assessed in fertile male CD-1 mice with the dominant lethal test. Each compound was assessed in a separate study. Male mice were exposed by inhalation to VC at 3000, 10,000, and 30,000 ppm and to VDC at 10, 30, and 50 ppm for 6 hr/day for 5 days. By comparison with control males exposed to air, no mutagenic effects on any maturation stage of spermatogenesis in treated males were detected. There was no significant increase in the number of postimplantational early fetal deaths as shown by the number of females with one or more early deaths or the number of early deaths/pregnancy or the number of early deaths/total implants/pregnancy. There was no evidence of pre-implantational egg losses as indicated by the total implants/pregnant female. There was also no reduction in fertility. (The reduction in fertility at 50 ppm VDC was unproven). The lack of effect was not due to the insensitivity of the system used, since both the VC and VDC study a mutagenic effect was clearly demonstrated in male mice dosed IP with the positive control compounds cyclophosphamide (CTX) and/or ethylmethane sulfonate (EMS). During dosing these animals were housed under similar exposure conditions to those animals exposed to the test substances but with a flow of air through the exposure chambers. Thus, neither VC nor VDC is mutagenic in the mouse at the stated exposure levels as measured by the dominant lethal test.
Anderson, Diana; Hodge, M. C. E.; Purchase, I. F. H.
A comparative study of free oligosaccharides in the milk of domestic animals.
The present study was conducted to obtain a comprehensive overview of oligosaccharides present in the milk of a variety of important domestic animals including cows, goats, sheep, pigs, horses and dromedary camels. Using an analytical workflow that included ultra-performance liquid chromatography-hydrophilic interaction liquid chromatography with fluorescence detection coupled to quadrupole time-of-flight MS, detailed oligosaccharide libraries were established. The partial or full characterisation of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar-specific exoglycosidases. Relative peak quantification of the 2-aminobenzamide-labelled oligosaccharides provided additional information. Milk from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed, and thirteen of these structures have been identified previously in human milk. The direct comparison of the oligosaccharide mixtures reflects their role in the postnatal maturation of different types of gastrointestinal systems, which, in this way, are prepared for certain post-weaning diets. The potential value of animal milk for the commercial extraction of oligosaccharides to be used in human and animal health is highlighted. PMID:24635885
Albrecht, Simone; Lane, Jonathan A; Marińo, Karina; Al Busadah, Khalid A; Carrington, Stephen D; Hickey, Rita M; Rudd, Pauline M
Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking
Aims: To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers. Methods: Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994–97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers. Results: Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (ORdairy = 1.26; OReggs = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OReggs was 2.88 among past smokers but only 1.46 for never smokers. The OReggs for current smokers of 0.80 might reflect self selection of exposure among smokers. Conclusions: Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.
Hoppin, J; Umbach, D; London, S; Alavanja, M; Sandler, D
The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment
Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies.
Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap
Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake), intermittent fasting (IF, every-other-day feeding), and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer's disease—with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function.
Dias, Gisele Pereira
Effects of diet on brain plasticity in animal and human studies: mind the gap.
Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake), intermittent fasting (IF, every-other-day feeding), and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer's disease-with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function. PMID:24900924
Murphy, Tytus; Dias, Gisele Pereira; Thuret, Sandrine
Re-Evaluate the Effect of Hyperbaric Oxygen Therapy in Cancer - A Preclinical Therapeutic Small Animal Model Study
Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.
Pande, Sneha; Sengupta, Amit; Srivastava, Anurag; Gude, Rajiv P.; Ingle, Arvind
This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.
Study on the Mechanical Instability of MICE Coupling Magnets
The superconducting coupling solenoid magnet is one of the key equipment in the Muon Ionization Cooling Experiment (MICE). The coil has an inner radius of 750 mm, length of 281 mm and thickness of 104 mm at room temperature. The peak in- duction in the coil is about 7.3 T with a full current of 210 A. The mechanical disturbances
Li Wang; Heng Pan; X. L. Guo; Hong Wu; Shi Xian Zheng; Michael A Green
Optical coherence tomography technique for noninvasive blood glucose monitoring: phantom, animal, and human studies
NASA Astrophysics Data System (ADS)
Continuous noninvasive monitoring of blood glucose concentration can improve management of Diabetes Mellitus, reduce mortality, and considerably improve quality of life of diabetic patients. Recently, we proposed to use the OCT technique for noninvasive glucose monitoring. In this paper, we tested noninvasive blood glucose monitoring with the OCT technique in phantoms, animals, and human subjects. An OCT system with the wavelength of 1300 nm was used in our experiments. Phantom studies performed on aqueous suspensions of polystyrene microspheres and milk showed 3.2% decrease of exponential slope of OCT signals when glucose concentration increased from 0 to 100 mM. Theoretical calculations based on the Mie theory of scattering support the results obtained in phantoms. Bolus glucose injections and glucose clamping experiments were performed in animals (New Zealand rabbits and Yucatan micropigs). Good correlation between changes in the OCT signal slope and actual blood glucose concentration were observed in these experiments. First studies were performed in healthy human subjects (using oral glucose tolerance tests). Dependence of the slope of the OCT signals on the actual blood glucose concentration was similar to that obtained in animal studies. Our studies suggest that the OCT technique can potentially be used for noninvasive blood glucose monitoring.
Larin, Kirill V.; Ashitkov, Taras V.; Larina, Irina V.; Petrova, Irina Y.; Eledrisi, Mohsen S.; Motamedi, Massoud; Esenaliev, Rinat O.
Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a micro-PET study.
The Brattleboro rat is an animal model of genetically induced central diabetes insipidus. These rats show cognitive and behavioral disorders, but no neurodegenerative disease has been observed. We studied brain glucose uptake, a marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats was studied in vivo and another group of animals was studied ex vivo. In vivo studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F-FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F-FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo (p<0.05), but only a trend towards higher values was found ex vivo. Our results show for the first time that brain glucose metabolism is modified in Brattleboro rats. This altered brain glucose metabolism in Brattleboro rats may be related to the observed cognitive and behavioral disorders. Functional analyses of brain metabolism are promising to investigate cognitive behavioral disturbances observed in Brattleboro rats and their link to diabetes insipidus. PMID:17559814
Idbaih, Ahmed; Burlet, Arlette; Adle-Biassette, Homa; Boisgard, Raphaël; Coulon, Christine; Paris, Sophie; Marie, Yannick; Donadieu, Jean; Hoang-Xuan, Khę; Ribeiro, Maria-Joao
Animal health studies using participatory epidemiology in the Mandrare Valley, Madagascar.
Pastoral herders in Madagascar have limited access to animal health workers and veterinary medicines, and more information on their livestock diseases is needed, so that effective animal health programmes can be implemented. In this study, participatory epidemiology methods were used to gather such information in the Mandrare Valley. These included pair-wise ranking and matrix scoring. Eleven diseases were deemed to be priorities by pair-wise ranking. Matrix scoring and characterisation showed that the informant groups associated many disease syndromes with the same diseases, indicating agreement and understanding of the key diseases. The Malagasy-named syndromes, Soko, Besorko and Mamany lio, which are gastrointestinal parasitism, clostridial disease and babesiosis, respectively, were identified by every informant group. A greater sample size may be needed to characterise the diseases precisely with matrix scoring because, in this study, the matrices' scores had wide confidence intervals. PMID:23999777
Bardsley, Elise L; Thrusfield, Michael V
Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica in experimental animals.
This study was aimed to provide pharmacological basis for the medicinal use of Phyllanthus emblica fruit in indigestion and constipation using the in-vivo and in-vitro assays. The crude extract of the dried fruits of Phyllanthus emblica (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300?mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea-pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration-dependent and partially atropine-sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003-0.1?mg/mL) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003-1.0?mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that the Phyllanthus emblica possesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use of Phyllanthus emblica fruits in indigestion and constipation. PMID:22972571
Mehmood, Malik Hassan; Rehman, Abdul; Rehman, Najeeb-Ur; Gilani, Anwarul-Hassan
Spontaneous acute tumor lysis syndrome as a cause of early deaths in short-term carcinogenicity studies using p53 +/- mice.
Acute tumor lysis syndrome (ATLS) is a potentially lethal condition precipitated by the massive release of intracellular components such as nucleic acids, potassium, and phosphorus, following a rapid and widespread lysis of tumor cells. Herein, the authors describe the high incidence and characteristic histopathologic lesions of acute ATLS in p53-deficient mice used in 2 short-term carcinogenicity studies. ATLS was a frequent cause of early death in p53 (+/-) mice in these studies and was consistently associated with the presence of disseminated lymphoma and leukemia. Although a heavy tumor burden and leukemia were present in all affected mice, the absence of ATLS in other mice with equally severe lymphoma and leukemia indicates that these tumor burdens are necessary but insufficient to cause ATLS in mice. The hallmark histopathologic findings of ATLS in mice are the disseminated microemboli composed of nuclear and cytoplasmic debris derived from lysed tumor cells. The mechanical obstruction of capillary beds by these microemboli appeared to be the proximate cause of the early deaths of mice in these studies. Microemboli may contribute to the pathogenesis of acute renal failure and other clinical signs associated with ATLS in other species. Recognition of ATLS in laboratory animals is critical in studies intended to evaluate the efficacy and/or toxicity of anticancer treatments, where early deaths due to ATLS might otherwise be attributed to test article toxicity. Further studies on the role of microemboli in the pathogenesis of ATLS may elucidate pathogenetic mechanisms and lead to improved approaches to clinical management and treatment of this potentially lethal condition. PMID:20435782
Vogel, P; Pletcher, J M; Liang, Y
Toxicological studies on Amfenac sodium (AHR-5850) (I) Acute toxicities in mice and rats.
Acute toxicities of Amfenac sodium (AHR-5850), new nonsteroidal anti-inflammatory agent, were studied in mice and rats. Each value of LD50 by oral, sc, im, iv and ip administration with this compound was 1190, 580, 540, 550 and 790 mg/kg for male mice and 1450, 625, 610, 630 and 710 mg/kg for female mice, respectively. Rats showed higher lethality than mice. There was no significant difference of sex in the values of LD50 for mice and rats. Movement and respiration rate followed by gastrointestinal ulcer, secondary peritonitis and systemic emaciation. These results suggest that the death is caused by secondary peritonitis and systemic emaciation due to gastrointestinal ulcer. PMID:6471132
Sasaki, H; Odaki, M; Yokota, M; Kawaoto, H; Watanabe, H; Itoh, T; Ishiwatari, N; Wada, T; Seki, M; Takeda, U
Study of DNA synthesis and mitotic activity of hepatocytes and its relation to angiogenesis in hepatectomised tumour bearing mice.
Partial hepatectomy (PH) alters serum concentrations of substances involved in cellular proliferation, leading to the compensatory liver hyperplasia. Furthermore, angiogenesis is mainly stimulated by vascular endothelial growth factor (VEGF) and is a fundamental requirement either in liver regeneration or in tumours growth. This study looks at the expression of VEGF, DNA synthesis (DNAs) and mitotic activity (MA) in hepatectomised (H) and hepatectomised-tumour bearing (HTB) mice throughout a 24?h period. Adult male mice were sacrificed every 4?h from 26 to 50?h post-hepatectomy. H mice show a circadian rhythm in VEGF expression with a maximum value of 2.6?±?0.1 at 08/46?h of day/hours posthepatectomy (HD/HPH); in DNAs, the maximum value was 3.4?±?0.3 at 16/30 (HD/HPH) and in MA it was 2.3?±?0.01 at 12/50 (HD/HPH). In HTB animals the peak of VEGF expression appears at 16/30 (HD/HPH) with a maximum value of 3.7?±?0.1, the peak of DNAs was at 00/38 (HD/HPH) with a value of 4.6?±?0.3 and the maximum value of MA of 08/46 (HD/HPH) with a value of 3.01?±?0.3. We can conclude that the presence of the tumour induces modifications in the intensity and the temporal distribution of the circadian curves of VEGF expression, DNAs and MA of hepatectomised animals. PMID:23881839
Andrini, Laura B; García, Marcela N; Inda, Ana María; Errecalde, Ana Lía
CorLink™ sutureless aortic anastomotic device: results of an animal study
Background. The CorLink™ Automated Anastomotic Device (AD) was developed to create a sutureless vein-to-aorta anastomosis without the need to clamp the aorta. This study examined the effectiveness and safety of this device in an animal model.Materials and methods. Forty-seven vein-to-aorta anastomoses using the AD and 27 control hand-sutured anastomoses were constructed in 28 sheep. The distal part of these grafts
Yaron Bar-El; Fermin O Tio; Rona Shofti
In vivo animal studies with gadolinium (III) texaphyrin as a radiation enhancer
Purpose: Gadolinium texaphyrin (Gd-Tex, PCI-0120) is an expanded porphyrin that has demonstrated radiation enhancement. In this study, we evaluated the radiation enhancement and biolocalization of Gd-Tex in three animal tumor models.Methods and Materials: EMT6, SMT-F, and MCa tumors were established intramuscularly or subcutaneously. Gd-Tex and other metallotexaphyrins were administered prior to single or multiple fractions of radiation. 14C-labeled Gd-Tex was
Richard A Miller; Kathryn Woodburn; Qing Fan; Markus F Renschler; Jonathan L Sessler; Jason A Koutcher
Wireless Intracranial Pressure Monitoring Through Scalp at Microwave Frequencies; Preliminary Phantom and Animal Study
Clinical determination of intracranial pressure (ICP) is critical to the management of head injuries and diseases of the brain (e.g., hydrocephalus), in order to avoid death and disability. The feasibility of acquiring intracranial pressure information through scalp at 2.4 GHz ISM band is demonstrated through in-vivo animal study. A previously fabricated device, including a piezoresistive sensor, an oscillator, and a
M.-R. Tofighi; U. Kawoos; F. A. Kralick; A. Rosen
Animal Origin Foods and Colorectal Cancer Risk: A Report From the Shanghai Women's Health Study
The association of animal-origin food consumption and cooking patterns with colorectal cancer (CRC) risk was evaluated in a cohort of 73,224 participants of the Shanghai Women's Health Study. After a mean follow-up time of 7.4 yr, 394 incident cases of CRC (colon = 236; rectal = 158) were diagnosed. Overall, no association was found between the risk of CRC and
Sang-Ah Lee; Xiao Ou Shu; Gong Yang; Honglan Li; Yu-Tang Gao; Wei Zheng
My Brother's Keeper A Case Study in Evolutionary Biology and Animal Behavior
NSDL National Science Digital Library
In this interrupted case study, students work in teams to interpret behavioral data with respect to evolutionary biology. Specifically, the case examines the behavior of alarm calling in a certain type of squirrel, Belding's ground squirrel, which was first reported by Paul Sherman in Science magazine in 1977. The case is appropriate for use in animal behavior, ecology, evolutionary biology, or introductory biology courses.
Benson, Kari E.
A study of cystic echinococcosis in slaughter animals in three selected areas of northern Turkana, Kenya
In an attempt to establish the prevalence of cystic echinococcosis, a study was conducted in slaughter animals in three divisions of northern Turkana, Kenya. A total of 5752 goats, 588 sheep, 381 cattle and 70 camels were examined at slaughter. Echinococcus granulosus metacestodes were found in 19.4% of the cattle, 3.6% of sheep, 4.5% of goats and 61.4% of camels.
E. M Njoroge; P. M. F Mbithi; J. M Gathuma; T. M Wachira; P. B Gathura; J. K Magambo; E Zeyhle
Herd-level interpretation of test results for epidemiologic studies of animal diseases
Correct classification of the true status of herds is an important component of epidemiologic studies and animal disease-control programs. We review theoretical aspects of herd-level testing through consideration of test performance (herd-level sensitivity, specificity and predictive values), the factors affecting these estimates, and available software for calculations. We present new aspects and considerations concerning the effect of precision and bias
Jette Christensen; Ian A. Gardner
Recurrent herpetic stromal keratitis in mice, a model for studying human HSK.
Herpetic eye disease, termed herpetic stromal keratitis (HSK), is a potentially blinding infection of the cornea that results in over 300,000 clinical visits each year for treatment. Between 1 and 2 percent of those patients with clinical disease will experience loss of vision of the infected cornea. The vast majority of these cases are the result of reactivation of a latent infection by herpes simplex type I virus and not due to acute disease. Interestingly, the acute infection is the model most often used to study this disease. However, it was felt that a recurrent model of HSK would be more reflective of what occurs during clinical disease. The recurrent animal models for HSK have employed both rabbits and mice. The advantage of rabbits is that they experience reactivation from latency absent any known stimulus. That said, it is difficult to explore the role that many immunological factors play in recurrent HSK because the rabbit model does not have the immunological and genetic resources that the mouse has. We chose to use the mouse model for recurrent HSK because it has the advantage of there being many resources available and also we know when reactivation will occur because reactivation is induced by exposure to UV-B light. Thus far, this model has allowed those laboratories using it to define several immunological factors that are important to this disease. It has also allowed us to test both therapeutic and vaccine efficacy. PMID:23271160
Morris, Jessica; Stuart, Patrick M; Rogge, Megan; Potter, Chloe; Gupta, Nipun; Yin, Xiao-Tang
[The study of tool use as the way for general estimation of cognitive abilities in animals].
Investigation of tool use is an effective way to determine cognitive abilities of animals. This approach raises hypotheses, which delineate limits of animal's competence in understanding of objects properties and interrelations and the influence of individual and social experience on their behaviour. On the basis of brief review of different models of manipulation with objects and tools manufacturing (detaching, subtracting and reshaping) by various animals (from elephants to ants) in natural conditions the experimental data concerning tool usage was considered. Tool behaviour of anumals could be observed rarely and its distribution among different taxons is rather odd. Recent studies have revealed that some species (for instance, bonobos and tamarins) which didn't manipulate tools in wild life appears to be an advanced tool users and even manufacturers in laboratory. Experimental studies of animals tool use include investigation of their ability to use objects physical properties, to categorize objects involved in tool activity by its functional properties, to take forces affecting objects into account, as well as their capacity of planning their actions. The crucial question is whether animals can abstract general principles of relations between objects regardless of the exact circumstances, or they develop specific associations between concerete things and situations. Effectiveness of laboratory methods is estimated in the review basing on comparative studies of tool behaviour, such as "support problem", "stick problem", "tube- and tube-trap problem", and "reserve tube problem". Levels of social learning, the role of imprinting, and species-specific predisposition to formation of specific domains are discussed. Experimental investigation of tool use allows estimation of the individuals' intelligence in populations. A hypothesis suggesting that strong predisposition to formation of specific associations can serve as a driving force and at the same time as obstacle to animals' activity is discussed. In several "technically gifted" species (such as woodpecker finches, New Caledonian crows, and chimpanzees) tool use seems to be guided by a rapid process of trial and error learning. Individuals that are predisposed to learn specific connections do this too quickly and thus become enslaved by stereotypic solutions of raising problems. PMID:16521567
Reznikova, Zh I
Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.
Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10g/kg bw. No death and abnormal behaviors occurred during 14days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7g/kg bw/day in both sexes of rats. PMID:24713262
Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan
Toxicology and NTP Carcinogenesis Studies of a Polybrominated Biphenyl Mixture (Firemaster FF-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
Firemaster FF-1, a flame retardant composed of polybrominated biphenyls (PBB), was responsible for widespread environmental contamination and animal losses in Michigan starting in 1973. This study was undertaken to characterize the long-term toxic and carcinogenic potential of this PBB mixture in rats and mice of each sex. Fisher 344/N rats and B6C3F1 mice were given 125 oral doses of PBB over a 6-month period--0, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg body weight/day (5 days/week). A dose-related decrease in body weight gain was observed in both male and female rats and male mice, although there was no significant difference in food consumption. At the end of the 6-month exposure, there was a dose-dependent decrease in thymus weights in rats. The liver appeared to be the primary target organ. Dose-related hepatotoxic effects were characterized by a marked increase in liver weight, with accentuation of hepatic lobular markings. Microscopically, there was moderate to marked hepatocellular swelling, disorganization and single cell necrosis of hepatocytes, fatty infiltration, and bile duct proliferation. At the 6-month observation, atypical hepatocellular foci were observed at a low incidence in dosed rats and mice. Hepatic porphyrin levels were markedly increased in both rats and mice, excessively in females. Levels of porphyrin tended to decrease gradually, primarily in mice, following cessation of exposure. The significant decreases in serum thyroxine (T4) and triiodothyronine (T3) in rats suggest that PBB may interfere with thyroid hormone secretion. Total serum protein was decreased in dose-related fashion in female rats primarily due to dose-related decreases in albumin. There was a significant increase in the serum levels of gamma glutamyl transpeptidase (GGTP) in female rats given 10.0 mg/kg of PBB. There was a dose-related decrease in serum glucose in female rats, a dose-related decrease in the serum triglyceride level in dosed male rats, except at the lowest dose (0.1 mg/kg), and a dose-related increase in the serum levels of cholesterol in both male and female rats. Serum levels of GGTP were increased only in female mice given 10.0 mg/kg of PBB. There was a 5- to 6-fold increase in the activity of serum glutamic pyruvic transaminase (SGPT) in male and female mice in the 10.0 mg/kg groups. Serum enzyme activity of alkaline phosphate (AP) was also increased in mice given the highest dose of PBB. There was a significant dose-related increase in the serum levels of cholesterol in female mice, and the highest dose group was significantly greater than the control female mice. Serum glucose was significantly decreased in female mice administered 10.0 mg/kg of PBB. To determine the carcinogenic potential of PBB, rats and mice dosed for 6 months were observed without exposure to PBB for an additional 23 or 24 months, respectively (lifetime observation). The dosing (0.3 mg/kg or higher dose levels) shortened the survival time in male rats, whereas no such effect was observed in dosed females. There was also evidence of shortened survival time in the 10.0 mg/kg PBB-dosed mice. A significantly higher incidence of atypical hepatocellular foci, neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas was observed in dosed rats. The incidence of hepatocellular carcinoma was increased in both male and female mice (highest dose level) compared with control male and female mice. The incidence of hepatic neoplasms appeared to be dose dependent in rats and mice. Liver tumors were observed primarily in those groups of animals to which PBB was given in doses sufficient to induce readily observable hepatic toxicity. Under the conditions of these studies, polybrominated biphenyl mixture (Firemaster FF-1) was carcinogenic for Fisher 344/N rats and B6C3F1 mice of each sex, inducing neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas in rats and hepatocellular carcinomas in mice. Other toxicities included porphyrogenic effects and hepatotoxicity. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female
Long-term effects of negative pions in female mice exposed to whole-body irradiation
Summary Long-term effects, especially the incidence of tumors, of whole-body exposure of female NMRI mice with either negative pions (peak or plateau region) or X rays have been studied in comparison to controls. Animals were irradiated at the age of 10 days after birth. The mice were then regularly examined for deaths and signs of severe disease, moribund animals being
A. Zimmermann; Ch. Michel; Ch. Stoller
Inhalation studies of Mt. St. Helens volcanic ash in animals. I. Introduction and exposure system
Due to the lack of information on the effects of inhaled Mt. St. Helens volcanic ash and its potential interaction with sulfur dioxide (SO/sub 2/), animal studies were performed to determine the acute and chronic health effects of a short-term exposure. This paper describes the inhalation exposure system designed for these studies and theoretically compares the pulmonary deposition in the rats to that in humans. Considering the similarities and differences in regional pulmonary deposition in humans and animals, inhalation studies were performed with fine-mode (less than 2.5 micron aerodynamic diameter, Dae) ash. Comparisons to coarse-mode (greater than 2.5 micron Dae) ash were made using intratracheal instillation. A whole-body exposure system was designed to provide inhalation exposures of animals to Mt. St. Helens volcanic ash, SO2, or a combination of both. All exposures were conducted using fine-mode ash samples generated by a Wright dust feed mechanism at a mean concentration of 9.4 mg/m/sup 3/ SD. Sulfur dioxide was maintained at 2.5 mg/m/sup 3/ SD. Scanning electron microscopy, X-ray diffraction, and X-ray fluorescence were used to characterize the ash.
Graham, J.A.; Miller, F.J.; Davies, D.W.; Hiteshew, M.E.; Walsh, L.C.
Inhalation studies of Mt. St. Helens volcanic ash in animals. I. Introduction and exposure system.
Due to the lack of information on the effects of inhaled Mt. St. Helens volcanic ash and its potential interaction with sulfur dioxide (SO2), animal studies were performed to determin