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1

Peromyscus leucopus mice: a potential animal model for haematological studies.  

PubMed

Peromyscus leucopus mice share physical similarities with laboratory mice Mus musculus (MM) but have higher agility and longer lifespan. We compared domesticated P. leucopus linville (PLL) and M. musculus C57BL/6 (MMB6) mice for cellular composition of peripheral blood (PB), bone marrow (BM) and spleen. PLL mice had significantly fewer platelets and significantly more monocytes in the blood, and notably fewer megakaryocytes in the BM. Spleens of PLL mice were significantly smaller, with 50% fewer cells and reduced 'red pulp'. There was no obvious haematological change in PLL mice between 2-8 and 16-26 months of age, except for a significant increase in blood monocytes. Cellular reactive oxygen species (ROS) content showed no change with age but differed significantly between different cell types. Treating two to eight month-old PLL mice with antioxidant N-acetylcysteine in drinking water for three months did not affect cellular ROS content, but increased blood leucocytes especially the concentration of monocytes. The low platelets, low megakaryocytes, high monocytes and low splenic erythropoiesis in PLL mice resemble human measurements better than the values seen in MMB6. PMID:25116892

Sun, Yu; Desierto, Marie J; Ueda, Yasutaka; Kajigaya, Sachiko; Chen, Jichun; Young, Neal S

2014-10-01

2

The role of hair in swimming of laboratory mice: implications for behavioural studies in animals  

E-print Network

. Since various hair and skin abnormalities are not uncommon in genetically modified or drug of genetically modified laboratory mouse and rat strains with abnormal hair makes the swim tests importantThe role of hair in swimming of laboratory mice: implications for behavioural studies in animals

Kalueff, Allan V.

3

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.

1969-01-01

4

Suspended animation-like state protects mice from lethal hypoxia.  

PubMed

Joseph Priestley observed the high burn rate of candles in pure oxygen and wondered if people would "live out too fast" if we were in the same environment. We hypothesize that sulfide, a natural reducer of oxygen that is made in many cell types, acts as a buffer to prevent unrestricted oxygen consumption. To test this, we administered sulfide in the form of hydrogen sulfide (H2S) to mice (Mus musculus). As we have previously shown, H2S decreases the metabolic rate of mice by approximately 90% and induces a suspended animation-like state. Mice cannot survive for longer than 20 min when exposed to 5% oxygen. However, if mice are first put into a suspended animation-like state by a 20-min pretreatment with H2S and then are exposed to low oxygen, they can survive for more than 6.5 h in 5% oxygen with no apparent detrimental effects. In addition, if mice are exposed to a 20-min pretreatment with H2S followed by 1 h at 5% oxygen, they can then survive for several hours at oxygen tensions as low as 3%. We hypothesize that prior exposure to H2S reduces oxygen demand, therefore making it possible for the mice to survive with low oxygen supply. These results suggest that H2S may be useful to prevent damage associated with hypoxia. PMID:17414418

Blackstone, Eric; Roth, Mark B

2007-04-01

5

Big mice die young but large animals live longer  

PubMed Central

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. PMID:23603822

Blagosklonny, Mikhail V.

2013-01-01

6

Toward an Animal Model for Antisocial Behavior: Parallels Between Mice and Humans  

Microsoft Academic Search

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

2003-01-01

7

Of ``mice'' and mammals: utilizing classical inbred mice to study the genetic architecture of function and  

E-print Network

Of ``mice'' and mammals: utilizing classical inbred mice to study the genetic architecture of function and performance in mammals Christopher J. Vinyard1, * and Bret A. Payseur *Department of Anatomy successful mammals and the premier research animal in mammalian biology. The classical inbred strains

Payseur, Bret

8

Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice  

PubMed Central

Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice. PMID:25414777

Jung, Yang-Hee; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; Lee, Ju-Hyun; Seo, Jee-Yeon; Lee, Seok-Yong; Jang, Choon-Gon

2014-01-01

9

DEVELOPMENTAL TOXICOGENOMIC STUDIES OF PFOA AND PFOS IN MICE.  

EPA Science Inventory

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are developmentally toxic in rodents. To better understand the mechanism(s) associated with this toxicity, we have conducted transcript profiling in mice. In an initial study, pregnant animals were dosed througho...

10

Shank mutant mice as an animal model of autism  

PubMed Central

In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism. PMID:24298145

Yoo, Juyoun; Bakes, Joseph; Bradley, Clarrisa; Collingridge, Graham L.; Kaang, Bong-Kiun

2014-01-01

11

Animal studies on Spacelab-3  

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.

1987-01-01

12

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.

13

Animal neuropsychology: Validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice  

Microsoft Academic Search

Research in animal neuropsychology is providing an exciting new generation of behavioral tests for mice that promise to overcome many of the limitations of current high-throughput testing, and provide direct animal homologues of clinically important measures in human research. Set shifting tasks are some of the best understood and widely used human neuropsychological tasks, with clinical relevance to traumatic brain

Joseph P. Garner; Collette M. Thogerson; Hanno Würbel; James D. Murray; Joy A. Mench

2006-01-01

14

Detection of Corynebacterium bovis infection in athymic nude mice from a research animal facility in Korea  

PubMed Central

Corynebacterium (C.) bovis infection in nude mice causes hyperkeratosis and weight loss and has been reported worldwide but not in Korea. In 2011, nude mice from an animal facility in Korea were found to have white flakes on their dorsal skin. Histopathological testing revealed that the mice had hyperkeratosis and Gram-positive bacteria were found in the skin. We identified isolated bacteria from the skin lesions as C. bovis using PCR and 16S rRNA sequencing. To the best of our knowledge, this is the first report of C. bovis infection in nude mice from Korea. PMID:24962412

Kim, Tae-Hyoun; Kim, Dong-Su; Han, Ju-Hee; Chang, Seo-Na; Kim, Kyung-Sul; Seok, Seung-Hyeok; Kim, Dong-Jae; Park, Jong-Hwan

2014-01-01

15

Thermal latency studies in opiate-treated mice  

PubMed Central

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. PMID:24459403

Schildhaus, Noam; Trink, Eliana; Polson, Chirs; DeTolla, Louis; Tyler, Betty M.; Jallo, George I.; Tok, Sino; Guarnieri, Michael

2014-01-01

16

Animal models of physiologic markers of male reproduction: genetically defined infertile mice  

SciTech Connect

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 the 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, the authors 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. They 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.

1987-10-01

17

Scanning multiple mice in a small-animal PET scanner: Influence on image quality  

NASA Astrophysics Data System (ADS)

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 can be expected. In this study, the NEMA NU 4-2008 image quality (NU4IQ) phantom and up to three FDG-filled cylindrical "mouse phantoms" were positioned in the FOV of the Siemens Inveon small-animal PET scanner to simulate scans with multiple mice. Five geometrical configurations were examined. In one configuration, the NU4IQ phantom was scanned separately and placed in the center of the FOV (1C). In two configurations, a mouse phantom was added with both phantoms displaced radially (2R) or axially (2A). In two other configurations, the NU4IQ phantom was scanned along with three mouse phantoms with all phantoms displaced radially (4R), or in a combination of radial and axial displacement (2R2A). Images were reconstructed using ordered subset expectation maximization in 2 dimensions (OSEM2D) and maximum a posteriori (MAP) reconstruction. Image quality parameters were obtained according to the NEMA NU 4-2008 guidelines. Optimum image quality was obtained for the 1C geometry. Image noise increased by the addition of phantoms and was the largest for the 4R configuration. Spatial resolution, reflected in the recovery coefficients for the FDG-filled rods, deteriorated by radial displacement of the NU4IQ phantom (2R, 2R2A, and 4R), most strongly for OSEM2D, and to a smaller extent for MAP reconstructions. Photon scatter, as indicated by the spill-over ratios in the non-radioactive water- and air-filled compartments, increased by the addition of phantoms, most strongly for the 4R configuration. Application of scatter correction substantially lowered the spill-over ratios, but caused an over-correction for the recovery coefficients of the FDG-filled rods when the phantom was displaced radially. Image noise was not substantially influenced by scatter correction. In conclusion, when scanning 2 mice, axial displacement (2A) is preferable above to radial displacement (2R) since for axial displacement, the recovery coefficients are higher and spill-over ratios are lower, whereas image noise remains similar. In the case of scanning 4 mice, combined axial and radial displacement (2R2A) is preferable to just radial displacement (4 R).

Siepel, Françoise J.; van Lier, Monique G. J. T. B.; Chen, Mu; Disselhorst, Jonathan A.; Meeuwis, Antoi P. W.; Oyen, Wim J. G.; Boerman, Otto C.; Visser, Eric P.

2010-09-01

18

Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease.  

PubMed

Mutations in the major facilitator superfamily domain containing 8 (MFSD8) gene coding for the lysosomal CLN7 membrane protein result in CLN7 disease, a lysosomal storage disease of childhood. CLN7 disease belongs to a group of inherited disorders, called neuronal ceroid lipofuscinoses (NCL), which are characterized by the accumulation of autofluorescent ceroid lipopigments, neuroinflammation, photoreceptor- and neurodegeneration. We have disrupted the Mfsd8 gene by insertion of a lacZ gene-trap cassette between exons 1 and 2 in mice and have analyzed the impact of Cln7 depletion on neuronal and visceral tissues. Analysis of lacZ reporter gene activity in heterozygous Mfsd8((wt/tm1a)) mice showed strong Mfsd8 mRNA expression in the cerebral cortex, in the hippocampus and in the kidney. Homozygous Mfsd8((tm1a/tm1a)) mice were viable and fertile and resembled biochemically the NCL-phenotype of human CLN7 patients including the accumulation of autofluorescent material in the brain and peripheral tissues and of subunit c of mitochondrial ATP synthase in the cerebellum and nuclei of distinct brain regions, and the degeneration of photoreceptor cells in the retina. Lysosomal storage was found in large neurons of the medulla, the hippocampus and in Purkinje cells of the cerebellum in mutant mice. The ultrastructure of the storage material revealed dense lamellar bodies with irregular forms within cerebellar and hippocampal neurons. In the brain loss of Cln7 was accompanied by mild reactive microgliosis and subtle astrogliosis by 10months of age, respectively. In summary we have generated a mouse model which is partly valuable as some but not all neuropathological features of human CLN7 disease are recapitulated thus representing an animal model to study CLN7-specific disease mechanisms. PMID:24423645

Damme, Markus; Brandenstein, Laura; Fehr, Susanne; Jankowiak, Wanda; Bartsch, Udo; Schweizer, Michaela; Hermans-Borgmeyer, Irm; Storch, Stephan

2014-05-01

19

Classification of human and animal strains of Fusobacterium necrophorum by their pathogenic effects in mice  

Microsoft Academic Search

Forty-six strains of Fusobacterium necrophorum, 24 from animals and 22 of human origin, were examined by pathogenicity tests in mice, while the same strains were being examined in laboratories elsewhere by other methods. The pathogenicity tests consisted of (1) subcutaneous inoculation with a large dose of a pure culture, (2) subcutaneous inoculation with a small dose of E necrophorum mixed

G. R. SMITH; E. A. THORNTON

1997-01-01

20

A SHAPE ANALYSIS FRAMEWORK FOR SMALL ANIMAL PHENOTYPING WITH APPLICATION TO MICE WITH A TARGETED DISRUPTION OF HOXD11  

E-print Network

analysis, Genetics, Biomedical imaging 1. INTRODUCTION Genetically modified mice have become commonplaceA SHAPE ANALYSIS FRAMEWORK FOR SMALL ANIMAL PHENOTYPING WITH APPLICATION TO MICE WITH A TARGETED as the variability in the positions where veins intersect, or the variabil- ity in animal skulls by the suture points

Utah, University of

21

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

PubMed Central

The involvement of autoreactive T cells in the pathogenesis of rheumatoid arthritis (RA) as well as in autoimmune animal models of arthritis has been well established; however, unanswered questions, such as the role of joint-homing T cells, remain. Animal models of arthritis are superb experimental tools in demonstrating how T cells trigger joint inflammation, and thus can help to further our knowledge of disease mechanisms and potential therapies. In this Review, we discuss the similarities and differences in T-cell subsets and functions between RA and mouse arthritis models. For example, various T-cell subsets are involved in both human and mouse arthritis, but differences might exist in the cytokine regulation and plasticity of these cells. With regard to joint-homing T cells, an abundance of synovial T cells is present in humans compared with mice. On the other hand, local expansion of type 17 T helper (TH17) cells is observed in some animal models, but not in RA. Finally, whereas T-cell depletion essentially failed in RA, antibody targeting of T cells can work, at least preventatively, in most arthritis models. Clearly, additional human and animal studies are needed to fill the gap in our understanding of the specific contribution of T-cell subsets to arthritis in mice and men. PMID:24394350

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

2014-01-01

22

Chemotherapy-induced peripheral neurotoxicity in immune-deficient mice: New useful ready-to-use animal models.  

PubMed

Cisplatin, paclitaxel and bortezomib are effective chemotherapy drugs in cancer treatment. However, they share severe peripheral neurotoxicity (PN) as one of their major dose-limiting side effects, often impairing cancer patients' quality of life and sometimes being permanent. Even if preclinical oncology is largely based on the use of immune-deficient mice, rodent models used to study the chemotherapy-induced PN are available only in immune-competent animals. In this study we characterized for the first time the PN induced by this chemotherapy through neurophysiological, behavioral, morphological and morphometric studies in athymic nude mice, a commonly employed strain in the preclinical oncology. The animals, divided into four groups, were chronically treated with cisplatin, paclitaxel or bortezomib once or twice a week for 4 or 6weeks or were left untreated. These schedules were tolerated, neurotoxic and in the range of antineoplastic effectiveness. Despite similarities, differences in the features of PN were evident if compared with immune-competent models under comparable regimens of treatment. The results of this study may provide a basis for future combined analysis of antineoplastic and neurotoxic effects of chemotherapy in the same animals. PMID:25450467

Carozzi, Valentina Alda; Chiorazzi, Alessia; Canta, Annalisa; Meregalli, Cristina; Oggioni, Norberto; Cavaletti, Guido; Marmiroli, Paola

2014-11-18

23

Clinical concepts derived from animal chemotherapy studies  

SciTech Connect

Animal chemotherapy studies have contributed significantly to clinical concepts in tumor therapy. Preclinical investigations have led to the discovery of new drugs and have demonstrated that it is possible to cure advanced metastatic neoplasia. A fundamental clinical concept stemming from animal chemotherapy studies is that increased selectivity and improved therapeutic effectiveness of antitumor agents may result from appropriate pharmacologic, biochemical, and biologic manipulation of the host-tumor drug relationship. Clinically important factors that may increase antitumor drug selectivity are reviewed and pertinent studies in animal model systems are cited.

Goldin, A.; Schabel, F.M.

1981-01-01

24

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

25

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.

1975-01-01

26

A Study of Statistical Errors in MICE  

SciTech Connect

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)

2010-03-30

27

Optimum Transfer Guide: Animal Science Why Study Animal Science?  

E-print Network

, nutrition, animal well being, breeding and genetics, physiology and with special- ties in cattle, horse approximately $35,000 in scholarships. Most of the scholarship money is set up in endow- ments ensuring that our

Gelfond, Michael

28

Record Keeping and Care for Animals in Study Areas Definitions  

E-print Network

on study areas http://wise.fau.edu/research/rcs/files/P4StudyAreas.doc 2. Tracking animals used in researchRecord Keeping and Care for Animals in Study Areas Definitions: Animal facility ­ a facility used to house animals full time and is registered with NIH and/or USDA Study area ­ an area where animals

Fernandez, Eduardo

29

Animals  

NSDL National Science Digital Library

Explore the wonderful world of animals Listen to the animal sound. See if you can identify the animal.Animal sounds. Explore and find out about different animals.Kids Planet Create a animal report using one of the animals found in the web site.Kids Planet,SeaWorld/animals Create a picture of your animal examples are found...Your big backyard ...

Mrs. Unsworth

2005-03-31

30

have knocked out the AID gene in mice, and found that these animals are normal  

E-print Network

CSR,asallknowncellular eventsleadinguptothisprocessarenormal. In complementary studies, Revy et al.1 have tracked down the gene that is mutated in a rare form of human immunodeficiency known as hyper-IgM syndrome -- a disease inwhichthe of this disease1 are very similar to the characteristics seen in the AID- knockout mice2 . The specific effect

Zare, Richard N.

31

Immunology and Homeopathy. 3. Experimental Studies on Animal Models  

PubMed Central

A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials. PMID:16786046

Bellavite, Paolo; Ortolani, Riccardo; Conforti, Anita

2006-01-01

32

Evidence of lung cancer risk from animal studies  

SciTech Connect

Human epidemiological data provide the most important basis for assessing risks of radon exposures. However, additional insight into the nature of exposure-response relationships is provided by animal experimentation and dosimetric determinations. Animal studies have now been conducted for more than 50 years to examine the levels of pollutants in underground mines that were responsible for the respiratory effects observed among miners. This work has emphasized respiratory cancer and the interaction of radon with other agents, such as ore dust, diesel-engine-exhaust fumes and cigarette smoke. The more recent data on radon-daughter inhalation exposures were provided by two American research centers, The University of Rochester (UR) and the Pacific Northwest Laboratory (PNL), and by the Compagnie Generale des Matieres Nucleaires (COGEMA) laboratory in France. Approximately 2000 mice, 100 rats and 80 dogs were employed in the completed UR studies, begun in the mid 1950s; 800 hamsters, 5000 rats and 100 dogs in the ongoing PNL studies, begun in the late 1960s; and 10,000 rats in the ongoing COGEMA studies, also begun in the late 1960s. More complete updated biological effects, data resulting from chronic radon-daughter inhalation exposures of mice, hamsters, rats and beagle dogs were examined. Emphasis on the carcinogenic effects of radon-decay product exposure, including the influences of radon-daughter exposure rate, unattached fraction and disequilibrium, and co-exposures to other pollutants. Plausible values for the radon (radon-daughter) lifetime lung-cancer risk coefficients are also provided. 13 refs., 1 fig., 1 tab.

Cross, F.T.

1988-03-01

33

Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study  

PubMed Central

Abstract It was reported using various biological models that the administration of blood factors from young animals to old animals could rejuvenate certain functions. To assess the anti-aging effect of young blood we tested the influence of repeated injections of plasma from young mice on the lifespan of aged mice. One group of 36 CBA/Ca female mice aged 10–12 months was treated by repeated injections of plasma from 2- to 4-month-old females (averaging 75–150??L per injection, once intravenously and once intraperitoneally per week for 16 months). Their lifespan was compared to a control group that received saline injections. The median lifespan of mice from the control group was 27 months versus 26.4 months in plasma-treated group; the repeated injections of young plasma did not significantly impact either median or maximal lifespan. PMID:25371859

Shytikov, Dmytro; Balva, Olexiy; Debonneuil, Edouard; Glukhovskiy, Pavel

2014-01-01

34

Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome  

SciTech Connect

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.

1987-11-01

35

Electron microscope study on the regenerative process of peripheral nerves of mice  

Microsoft Academic Search

An electron microscope study of the reactive process taking place in the proximal segment of sectioned dorso-spinal nerves of white mice was carried out in about 50 animals. Attention was mainly directed to the study of the earliest changes (30') observable in the neuroplasm but the series of experiments included the study of nerves fixed up to 20 days after

R. Wettstein; J. Roberto Sotelo

1963-01-01

36

Animal models of anxiety disorders in rats and mice: some conceptual issues  

PubMed Central

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. PMID:22275854

Steimer, Thierry

2011-01-01

37

Transgenic mice with increased Cu\\/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome  

Microsoft Academic Search

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

C. J. Epstein; K. B. Avraham; M. Lovett; S. Smith; O. Elroy-Stein; G. Rotman; C. Bry; Y. Groner

1987-01-01

38

Transgenic Mice with Increased Cu\\/Zn-Superoxide Dismutase Activity: Animal Model of Dosage Effects in Down Syndrome  

Microsoft Academic Search

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. These animals express the transgene

Charles J. Epstein; Karen B. Avraham; Michael Lovett; Sandra Smith; Orna Elroy-Stein; Galit Rotman; Cheryl Bry; Yoram Groner

1987-01-01

39

MOSFET assessment of radiation dose delivered to mice using the Small Animal Radiation Research Platform (SARRP).  

PubMed

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

2011-12-01

40

Animal escapology II: escape trajectory case studies  

PubMed Central

Summary Escape trajectories (ETs; measured as the angle relative to the direction of the threat) have been studied in many taxa using a variety of methodologies and definitions. Here, we provide a review of methodological issues followed by a survey of ET studies across animal taxa, including insects, crustaceans, molluscs, lizards, fish, amphibians, birds and mammals. Variability in ETs is examined in terms of ecological significance and morpho-physiological constraints. The survey shows that certain escape strategies (single ETs and highly variable ETs within a limited angular sector) are found in most taxa reviewed here, suggesting that at least some of these ET distributions are the result of convergent evolution. High variability in ETs is found to be associated with multiple preferred trajectories in species from all taxa, and is suggested to provide unpredictability in the escape response. Random ETs are relatively rare and may be related to constraints in the manoeuvrability of the prey. Similarly, reports of the effect of refuges in the immediate environment are relatively uncommon, and mainly confined to lizards and mammals. This may be related to the fact that work on ETs carried out in laboratory settings has rarely provided shelters. Although there are a relatively large number of examples in the literature that suggest trends in the distribution of ETs, our understanding of animal escape strategies would benefit from a standardization of the analytical approach in the study of ETs, using circular statistics and related tests, in addition to the generation of large data sets. PMID:21753040

Domenici, Paolo; Blagburn, Jonathan M.; Bacon, Jonathan P.

2011-01-01

41

Animal escapology II: escape trajectory case studies.  

PubMed

Escape trajectories (ETs; measured as the angle relative to the direction of the threat) have been studied in many taxa using a variety of methodologies and definitions. Here, we provide a review of methodological issues followed by a survey of ET studies across animal taxa, including insects, crustaceans, molluscs, lizards, fish, amphibians, birds and mammals. Variability in ETs is examined in terms of ecological significance and morpho-physiological constraints. The survey shows that certain escape strategies (single ETs and highly variable ETs within a limited angular sector) are found in most taxa reviewed here, suggesting that at least some of these ET distributions are the result of convergent evolution. High variability in ETs is found to be associated with multiple preferred trajectories in species from all taxa, and is suggested to provide unpredictability in the escape response. Random ETs are relatively rare and may be related to constraints in the manoeuvrability of the prey. Similarly, reports of the effect of refuges in the immediate environment are relatively uncommon, and mainly confined to lizards and mammals. This may be related to the fact that work on ETs carried out in laboratory settings has rarely provided shelters. Although there are a relatively large number of examples in the literature that suggest trends in the distribution of ETs, our understanding of animal escape strategies would benefit from a standardization of the analytical approach in the study of ETs, using circular statistics and related tests, in addition to the generation of large data sets. PMID:21753040

Domenici, Paolo; Blagburn, Jonathan M; Bacon, Jonathan P

2011-08-01

42

Why the Study of Animal Behavior Is Associated with the Animal Welfare Issue  

Microsoft Academic Search

Of the various disciplines within the modate normal behavior. The issue of behavioral animal sciences, the issue of animal welfare has been needs has been addressed and research interest in most closely associated with ethology, the study of motivation has developed. Preference tests have been animal behavior. Prior to the modern welfare move- used for their traditional role of improving

Harold W. Gonyou

2009-01-01

43

Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals.  

PubMed

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. PMID:23640454

Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L M T; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

2013-01-01

44

Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals  

PubMed Central

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. PMID:23640454

Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

2013-01-01

45

A carcinogenicity study of instant coffee in Swiss mice.  

PubMed

Commercially available regular instant coffee was given in the diet to barrier-maintained, specified pathogen-free Swiss mice for 2 yr. Groups of 150 males and 150 females were fed diets containing 10, 25 or 50 g instant coffee powder/kg. The animals had already been exposed to coffee in utero. Coffee increased the energy expenditure of the animals as shown by increased daily calorific intake and depressed growth. The overall tumour incidence was inversely correlated to the coffee intake, and no unusual tumour or site of origin was found. The most frequent neoplasms were lymphosarcomas, bronchiolo-alveolar adenomas and adenocarcinomas, as well as hepatocellular adenomas. The incidence of total neoplasms (benign and malignant) decreased from 70.6 and 56.8% in control males and females, respectively, to 34.8 and 36.2%, respectively, in the high-dose group. This decrease, which was essentially due to a reduction in the number of lymphosarcomas and hepatocellular adenomas, was associated with a slower growth rate. The number of leiomyomas in the uterus was slightly increased due to coffee intake as shown by the analysis of positive trend (P less than or equal to 0.05). However, the incidence of this benign tumour was very low; 2.72% of mice affected in the high-dose group, 1.37% in the low-dose group and 0% in the control and medium-dose groups. From this study it is concluded that instant coffee did not increase the incidence of malignant neoplasms in mice when fed at dietary levels of up to 5% for 2 yr. PMID:2148922

Stalder, R; Bexter, A; Würzner, H P; Luginbühl, H

1990-12-01

46

Biosimilars entering the clinic without animal studies.  

PubMed

The concept of biosimilars has spread from Europe to other regions throughout the world, and many regions have drafted regulatory guidelines for their development. Recently, a paradigm shift in regulatory thinking on the non-clinical development of biosimilars has emerged in Europe: In vivo testing should follow a step-wise approach rather than being performed by default. To not require animal testing at all in some instances can well be seen as a revolutionary, but science-based, step. Here, we describe the internal discussions that led to this paradigm shift. The mainstay for the establishment of biosimilarity is the pharmaceutical comparability based on extensive physicochemical and biological characterization. Pharmacodynamic comparability can be evaluated in in vitro assays, whereas pharmacokinetic comparability is best evaluated in clinical studies. It is considered highly unlikely that new safety issues would arise when comparability has been demonstrated based on physicochemical and in vitro comparative studies. PMID:25517301

van Aerts, Leon Agjm; De Smet, Karen; Reichmann, Gabriele; van der Laan, Jan Willem; Schneider, Christian K

2014-09-01

47

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.

2001-01-01

48

Animation  

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).

49

Animal Studies Last updated: 1st July 2009  

E-print Network

Animal Studies Last updated: 1st July 2009 1. Purpose of the collection The Gatton LibraryDirect (Elsevier) 4. Interdisciplinary relationships The School of Animal Studies shares common areas of interest collection in this area is intended to support the teaching and research activities of the School of Animal

Blows, Mark

50

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

2000-01-01

51

Guidelines for Diet Control in Behavioral Animal Studies Introduction  

E-print Network

1 Guidelines for Diet Control in Behavioral Animal Studies Introduction The purpose the period of study. Behavioral research often requires that an animal perform a task for which it receives, performing a task for reinforcement is behaviorally enriching for laboratory animals. As noted in the Guide

Bandettini, Peter A.

52

Interferon ?/? receptor knockout mice as a model to study bluetongue virus infection.  

PubMed

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

2014-03-01

53

Study of hepatitis C virus entry in genetically humanized mice  

PubMed Central

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

2013-01-01

54

ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY  

PubMed Central

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. PMID:24553602

Loría-Cervera, Elsy Nalleli; Andrade-Narváez, Fernando José

2014-01-01

55

Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans  

SciTech Connect

For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals.

Price, Paul S. [Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland MI 48674 (United States)], E-mail: pprice@dow.com; Keenan, Russell E. [AMEC Earth and Environmental, 15 Franklin Street, Portland, ME 04101 (United States); Swartout, Jeffrey C. [National Center for Environmental Assessment U.S. Environmental Protection Agency, 26 W. M. L. King Drive, Cincinnati, OH 45268 (United States)

2008-11-15

56

Gene Expression Changes in the Olfactory Bulb of Mice Induced by Exposure to Diesel Exhaust Are Dependent on Animal Rearing Environment  

PubMed Central

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. PMID:23940539

Yokota, Satoshi; Hori, Hiroshi; Umezawa, Masakazu; Kubota, Natsuko; Niki, Rikio; Yanagita, Shinya; Takeda, Ken

2013-01-01

57

Gene expression changes in the olfactory bulb of mice induced by exposure to diesel exhaust are dependent on animal rearing environment.  

PubMed

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/m(3), 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. PMID:23940539

Yokota, Satoshi; Hori, Hiroshi; Umezawa, Masakazu; Kubota, Natsuko; Niki, Rikio; Yanagita, Shinya; Takeda, Ken

2013-01-01

58

Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease.  

PubMed

Lafora progressive myoclonous epilepsy (Lafora disease; LD) is caused by mutations in the EPM2A gene encoding a dual specificity protein phosphatase named laforin. Our analyses on the Epm2a gene knock-out mice, which developed most of the symptoms of LD, reveal the presence of hyperphosphorylated Tau protein (Ser(396) and Ser(202)) as neurofibrillary tangles (NFTs) in the brain. Intriguingly, NFTs were also observed in the skeletal muscle tissues of the knock-out mice. The hyperphosphorylation of Tau was associated with increased levels of the active form of GSK3 beta. The observations on Tau protein were replicated in cell lines using laforin overexpression and knockdown approaches. We also show here that laforin and Tau proteins physically interact and that the interaction was limited to the phosphatase domain of laforin. Finally, our in vitro and in vivo assays demonstrate that laforin dephosphorylates Tau, and therefore laforin is a novel Tau phosphatase. Taken together, our study suggests that laforin is one of the critical regulators of Tau protein, that the NFTs could underlie some of the symptoms seen in LD, and that laforin can contribute to the NFT formation in Alzheimer disease and other tauopathies. PMID:19542233

Puri, Rajat; Suzuki, Toshimitsu; Yamakawa, Kazuhiro; Ganesh, Subramaniam

2009-08-21

59

Animation  

Microsoft Academic Search

\\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

60

Studying Biotechnological Methods Using Animations: The Teacher's Role  

ERIC Educational Resources Information Center

Animation has great potential for improving the way people learn. A number of studies in different scientific disciplines have shown that instruction involving computer animations can facilitate the understanding of processes at the molecular level. However, using animation alone does not ensure learning. Students sometimes miss essential features…

Yarden, Hagit; Yarden, Anat

2011-01-01

61

Rodents for comparative aging studies: from mice to beavers  

Microsoft Academic Search

After humans, mice are the best-studied mammalian species in terms of their biology and genetics. Gerontological research\\u000a has used mice and rats extensively to generate short- and long-lived mutants, study caloric restriction and more. Mice and\\u000a rats are valuable model organisms thanks to their small size, short lifespans and fast reproduction. However, when the goal\\u000a is to further extend the

Vera Gorbunova; Michael J. Bozzella; Andrei Seluanov

2008-01-01

62

CENSHARE - Center to Study Human Animal Relationships and Environments  

NSDL National Science Digital Library

Established in 1981 at the University of Minnesota's School of Public Health, the Center to Study Human Animal Relationships and Environments (CENSHARE) is an umbrella organization that supports groups that aim to educate about the human animal relationship and the environment they share. This mission of this education is to improve the quality of life for both, encourage scientific study of such relationships, and also serve as a resource for the community on these relationships. Visitors should check out the thorough explanation of "Animal Assisted Therapy" (AAT), and learn how it differs from, say, Animal Assisted Activities (AAA). As animal therapy can be stressful on the animal if it is not properly trained for such demanding work, the AAT link gives helpful tips to visitors on how to get an animal ready to be a therapy animal. Visitors will also learn from the AAT link that such animals have been evaluated and registered by national groups that specialize in therapy animals, but are not given the federal protections that specially-trained service dogs are, such as access to public transportation and public buildings. Finally, visitors should check out the "Companion Animals in Care Environments" link. Here they can read a bittersweet story titled "Lessons to be Learned from the Saga of Mae" which addresses the considerations that should be made when deciding whether to allow a resident animal in a care facility.

63

Assessing clinical prospects of silicon quantum dots: studies in mice and monkeys.  

PubMed

Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots. PMID:23841561

Liu, Jianwei; Erogbogbo, Folarin; Yong, Ken-Tye; Ye, Ling; Liu, Jing; Hu, Rui; Chen, Hongyan; Hu, Yazhuo; Yang, Yi; Yang, Jinghui; Roy, Indrajit; Karker, Nicholas A; Swihart, Mark T; Prasad, Paras N

2013-08-27

64

Pancreatic Insulin-Producing Cells Differentiated from Human Embryonic Stem Cells Correct Hyperglycemia in SCID/NOD Mice, an Animal Model of Diabetes  

PubMed Central

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. PMID:25009980

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

2014-01-01

65

Exploratory study of oral mucosal colonization of human gastric Helicobacter pylori in mice  

PubMed Central

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. PMID:24753744

Wan, Xueqin; Tang, Dongsheng; Zhang, Xiaohuan; Li, Hongming; Cui, Zhixin; Hu, Sijuan; Huang, Ming

2014-01-01

66

Animations  

NSDL National Science Digital Library

This collection contains animations of a nuclear chain reaction, nuclear fission and nuclear fusion. It also showcases interactive models of the first atomic bombs and simulation of the "Nuclear Winter" effect.

Christopher Griffith

67

Stanford study shows anxiety increases cancer severity in mice  

Cancer.gov

In a new study led by researchers at the Stanford University School of Medicine, anxiety-prone mice developed more severe cancer then their calm counterparts. The study, published online April 25 in PLoS ONE, found that after hairless mice were dosed with ultraviolet rays, the nervous ones — with a penchant for reticence and risk aversion — developed more tumors and invasive cancer.

68

Studies on induction of lamotrigine metabolism in transgenic UGT1 mice  

PubMed Central

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. PMID:19845433

Argikar, U. A.; Senekeo-Effenberger, K.; Larson, E. E.; Tukey, R. H.; Remmel, R. P.

2010-01-01

69

Hydration with Saline Decreases Toxicity of Mice Injected With Calcitriol in Preclinical Studies  

PubMed Central

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. PMID:24266410

Azari, Amir A; Kanavi, Mozhgan R.; Darjatmoko, Soesiawati R.; Lee, Vivian; Kim, KyungMann; Potter, Heather D.; Albert, Daniel M.

2014-01-01

70

Metabolomic analysis of long-term spontaneous exercise in mice suggests increased lipolysis and altered glucose metabolism when animals are at rest.  

PubMed

Exercise has been associated with several beneficial effects and is one of the major modulators of metabolism. The working muscle produces and releases substances during exercise that mediate the adaptation of the muscle but also improve the metabolic flexibility of the complete organism, leading to adjustable substrate utilization. Metabolomic studies on physical exercise are scarce and most of them have been focused on the effects of intense exercise in professional sportsmen. The aim of our study was to determine plasma metabolomic adaptations in mice after a long-term spontaneous exercise intervention study (18 mo). The metabolic changes induced by long-term spontaneous exercise were sufficient to achieve complete discrimination between groups in the principal component analysis scores plot. We identified plasma indicators of an increase in lipolysis (elevated unsaturated fatty acids and glycerol), a decrease in glucose and insulin plasma levels and in heart glucose consumption (by PET), and altered glucose metabolism (decreased alanine and lactate) in the wheel running group. Collectively these data are compatible with an increase in skeletal muscle insulin sensitivity in the active mice. We also found an increase in amino acids involved in catecholamine synthesis (tyrosine and phenylalanine), in the skeletal muscle pool of creatine phosphate and taurine, and changes in phospholipid metabolism (phosphocholine and choline in lipids) between the sedentary and the active mice. In conclusion, long-term spontaneous wheel running induces significant plasma and tissue (heart) metabolic responses that remain even when the animal is at rest. PMID:25190738

Monleon, Daniel; Garcia-Valles, Rebeca; Morales, Jose Manuel; Brioche, Thomas; Olaso-Gonzalez, Gloria; Lopez-Grueso, Raul; Gomez-Cabrera, Mari Carmen; Viña, Jose

2014-11-15

71

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  

PubMed Central

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

2014-01-01

72

Studies on the diversity of soil animals in Taishan Mountain  

Microsoft Academic Search

Taishan Mountain has diverse habitats and abundant groups of soil animals. Five habitats,Platycladus orientalis forest,Pinus densiflora forest,Robinia pseudoacacia forest,Pinus tablaerormis forest and Grassland, were selected and the diversity of soil animals in different habitats in Mt. Taishan were investigated\\u000a and studied in 1997–1999. Totally 52 groups of soil animals were found, belonging separately to 7 Phyla, 11 Classes, 25 Orders

Yuan Xing-zhong; Liu Hong

2000-01-01

73

Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an immunohistochemical study.  

PubMed

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone macrophages (MOMA-1). All macrophages were negative for the scavenger receptor MARCO and 50% were positive for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for more than 70% CD4-positive. ICAM-1 was positive both in atherosclerotic and control mice. In early plaques, fibrosis was observed on the luminal and medial site of the foam cells while smooth muscle cells were only observed in the fibrous cap. To study regression, we used a high fat, high cholesterol diet to rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow. Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels dropped in 4 weeks to control levels. The animals did not show a significantly decrease in plaque size over time. but the percentage macrophages was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leiden mouse is a useful model to study the progression and regression of atherosclerosis. PMID:10208477

Gijbels, M J; van der Cammen, M; van der Laan, L J; Emeis, J J; Havekes, L M; Hofker, M H; Kraal, G

1999-03-01

74

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

2000-01-01

75

Wound-healing studies in transgenic and knockout mice  

Microsoft Academic Search

Injury to the skin initiates a cascade of events including inflammation, new tissue formation, and tissue remodeling, that\\u000a finally lead to at least partial reconstruction of the original tissue. Historically, animal models of repair have taught\\u000a us much about how this repair process is orchestrated and, over recent years, the use of genetically modified mice has helped\\u000a define the roles

Richard Grose; Sabine Werner

2004-01-01

76

GUIDELINE FOR COMPLETING THE NIH INTRAMURAL ANIMAL STUDY PROPOSAL FORM  

E-print Network

(AWA) Regulations and the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) require review and approval of an Animal Study Proposal (ASP) by the Institute/Center (IC of the ASP form, but are targeted to new investigators. The goal of this guideline is to help an investigator

Bandettini, Peter A.

77

Empirical Studies of Animation-embedded Hypermedia Algorithm Visualizations  

E-print Network

1 Empirical Studies of Animation-embedded Hypermedia Algorithm Visualizations Steven Hansen, Daniel Schrimpsher, N. Hari Narayanan and Mary Hegarty Technical Report CSE98-06 November 4, 1998 Visual Information of Animation-embedded Hypermedia Algorithm Visualizations Steven Hansen, N. Hari Narayanan, and Daniel

78

A qualitative study of animation programming in the wild  

Microsoft Academic Search

Scratch is the latest iteration in a series of animation tools aimed at teaching programming skills. Scratch, in particular, aims not only to teach technical skills, but also skills related to collaboration and code reuse. In order to assess the strengths and weaknesses of Scratch relative to these goals, we have performed an empirical field study of Scratch animations and

Aniket Dahotre; Yan Zhang; Christopher Scaffidi

2010-01-01

79

GPS ERROR IN STUDIES ADDRESSING ANIMAL MOVEMENTS AND ACTIVITES  

Technology Transfer Automated Retrieval System (TEKTRAN)

One concern in animal behavior studies employing global positioning system (GPS) collars centers on effects of GPS error on measures of animal movement. Errors may be additive over time and potentially intensify with high frequency sampling or fine scale movements. We addressed issues related to t...

80

Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals  

Microsoft Academic Search

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

Tamás RoSzer; Éva Pintye; Ilona Benko

2008-01-01

81

John Buckley, Animal Technician  

Cancer.gov

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.

82

Animal Models to Study Gluten Sensitivity1  

PubMed Central

The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease. PMID:22572887

Marietta, Eric V.; Murray, Joseph A.

2012-01-01

83

Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD.  

PubMed

Non-alcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that includes a wide spectrum of morphological alterations. In research, animal models are crucial in evaluating not only the pathogenesis of NAFLD and its progression, but also the therapeutic effects of various agents. Investigations on the ultrastructural features of NAFLD in humans are not copious, due to the difficulty to obtain human samples and to the long time of NAFLD to evolve. Translational comparative studies on the reliability of animal models in representing the histopathologic picture as seen in humans are missing. To overcome this lack of investigations, we compared the ultrastructural NAFLD features of an animal model versus human. Sprague-Dawley rats were fed with a high fat diet (HFD) for 1-4 weeks, while control rats were fed with a standard diet. Human specimens were collected from patients with diagnosed fatty liver disease, undergoing liver biopsies or surgery. Rat and human samples were examined by light microscopy and by transmission and high resolution scanning electron microscopy. The present work demonstrated that NAFLD in animal model and in human, share overlapping ultrastructural features. In conclusion, animal HFD represent an appropriate tool in studying the pathogenesis of NAFLD. PMID:25044260

Solinas, Paola; Isola, Michela; Lilliu, Maria Alberta; Conti, Gabriele; Civolani, Alberto; Demelia, Luigi; Loy, Francesco; Isola, Raffaella

2014-10-01

84

Animal PerformancesAn Exploration of Intersections between Feminist Science Studies and Studies of Human\\/Animal Relationships  

Microsoft Academic Search

Feminist science studies have given scant regard to non-human animals. In this paper, we argue that it is important for feminist theory to address the complex relationships between humans and other animals, and the implications of these for feminism. We use the notion of performativity, particularly as it has been developed by Karen Barad, to explore the intersections of feminism

Lynda Birke; Mette Bryld; Nina Lykke

2004-01-01

85

Of mice and men (and women and children): Scientific and ethical implications of animal models  

Microsoft Academic Search

1.1. Animal models of human behavior and disease are commonly used and have contributed significantly to progress in understanding the physiological mechanisms of both normal function and disease, and in the development of effective therapies.2.2. Little attention has been given, however, to the scientific and ethical implications of choosing a particular animal model.3.3. This paper discusses the rationale for the

Stephanie J. Bird; Mary Brown Parlee

2000-01-01

86

An Animal Model of Chronic Aplastic Bone Marrow Failure Following Pesticide Exposure in Mice  

PubMed Central

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. PMID:24855541

Chatterjee, Sumanta; Chaklader, Malay; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaudhuri, Samaresh; Law, Sujata

2010-01-01

87

Collagen studies in late pregnant relaxin null mice.  

PubMed

The relaxin knockout (rlx -/-) mouse was used to assess the effect, during pregnancy, of relaxin with regard to water, collagen content, growth, and morphology of the nipple (N), vagina (V), uterus, cervix (C), pubic symphysis (PS), and mammary gland (MG). The results presented here indicate that during pregnancy, relaxin increases the growth of the N, C, V, and PS. Large increases in water content in the PS (20%) occurred in pregnant (Day 18.5) wild-type (rlx +/+) mice but not in rlx -/- animals. This indicates that in the PS, relaxin might increase the concentration of a water-retaining extracellular matrix component (hyaluronate). In the pregnant rlx +/+ mouse, collagen content decreased significantly in the N and V but not in other tissues. There were no significant changes in the rlx -/- mouse. This contrasts with findings in the rat, in which relaxin has been found to cause decreases in collagen concentrations in the V, C, and PS. Histological analysis showed that the collagen stain was more condensed in the tissues (V, C, PS, N, and MG) of rlx -/- mice than in those of rlx +/+ mice. This phenomenon indicates that the failure of collagen degradation and lack of growth in the N underlie the inability of the rlx -/- mice to feed their young, as reported previously. Vaginal and cervical luminal epithelia, which proliferated markedly in the rlx +/+ pregnant mice, remained relatively atrophic in the rlx -/- mice. As proliferation and differentiation of uterine and vaginal epithelia are thought to be induced by a paracrine stromal factor that acts upon estrogen stimulation, our results indicate that relaxin may be this paracrine factor. PMID:10952910

Zhao, L; Samuel, C S; Tregear, G W; Beck, F; Wintour, E M

2000-09-01

88

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

NASA Technical Reports Server (NTRS)

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

Sonnenfeld, Gerald

2005-01-01

89

Controlling airborne cues to study small animal navigation  

PubMed Central

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). PMID:22245808

Gershow, Marc; Berck, Matthew; Mathew, Dennis; Luo, Linjiao; Kane, Elizabeth A.; Carlson, John R.; Samuel, Aravinthan D.T.

2012-01-01

90

Automated, quantitative cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction.  

PubMed

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be controlled by one computer. PMID:24637442

Gallistel, C R; Balci, Fuat; Freestone, David; Kheifets, Aaron; King, Adam

2014-01-01

91

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.

2014-01-01

92

Acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice: a comparative study.  

PubMed

Lungs play an important role in the body's defense against a variety of pathogens, but this network of immune system-mediated defense can be deregulated during acute pulmonary infections. The present study compares acute lung inflammation occurring during Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice. Pneumonia was induced by intranasal instillation of bacteria (10(4) cfu), while sepsis was developed by placing the fibrin-thrombin clot containing known amount of bacteria (10(2) cfu) into the peritoneal cavity of animals. Mice with sepsis showed 100% mortality within five post-infection days, whereas all the animals with pneumonia survived. In animals suffering from K. pneumoniae B5055-induced pneumonia, all the inflammatory parameters (TNF-?, IL-1?, MPO, MDA, and NO) were found to be maximum till third post-infection day, after that, a decline was observed, whereas in septic animals, all the above-mentioned markers of inflammation kept on increasing. Histopathological study showed presence of alternatively activated alveolar macrophages (or foam cells) in lungs of mice with pneumonia after third post-infection day, which might have contributed to the induction of resolution of inflammation, but no such observation was made in lungs of septic mice. Hence, during pneumonia, controlled activation of macrophages may lead to resolution of inflammation. PMID:20890649

Kumar, Vijay; Chhibber, Sanjay

2011-10-01

93

Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.  

PubMed

Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit. PMID:23103401

Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

2013-02-01

94

An Animal Model of Type A Cystinuria Due to Spontaneous Mutation in 129S2/SvPasCrl Mice  

PubMed Central

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. PMID:25048459

Livrozet, Marine; Vandermeersch, Sophie; Mesnard, Laurent; Thioulouse, Elizabeth; Jaubert, Jean; Boffa, Jean-Jacques; Haymann, Jean-Philippe; Baud, Laurent; Bazin, Dominique; Daudon, Michel; Letavernier, Emmanuel

2014-01-01

95

BALB\\/c and C57Bl\\/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis  

Microsoft Academic Search

Burkholderia pseudomalleiis the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB\\/c and C57Bl\\/6 mice as animal models for the different forms of human melioidosis. The course of

Alison K Leakey; Glen C Ulett; Robert G Hirst

1998-01-01

96

Rodents for comparative aging studies: from mice to beavers  

PubMed Central

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

Bozzella, Michael J.; Seluanov, Andrei

2008-01-01

97

[Acute and subacute toxicity studies of tris (1,3-dichloro-2-propyl) phosphate on mice].  

PubMed

Slc/ddY mice (10 male, 10 female per group) were given a single p.o. intubation of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) in olive oil and were observed for 14 days. LD50 values of male and female mice were 2.67 (2.52 approximately 2.83) and 2.25 2.25 (2.12 approximately 2.39) g/kg, respectively. The animals revealed ataxic gait, hyperactivity, and convulsion. Slc/ddY mice (12 male, 12 female er group) were administered diet containing 1.33, 0.42, 0.13, 0.04, and 0.01% of TDCPP for 3 months. Male and female mice of the 1.33% group showed emaciation, rough hair, and tremor; and all animals died within one month. Hematological studies showed slight anemia in males of the 0.42% group and females of the 0.42% and 0.13% groups. They also exhibited a tendency to increase ALP and GPT levels. The animals of the 0.42%, 0.13% and 0.04% groups exhibited tendency to increase liver weights and kidney weights in both sexes. Histopathologically, very slight focal necrosis was recognized in the liver in only 2 females of the 0.42% group. The NOEL under this condition is 0.01% in the diet of tris (1,3-dichloro-2-propyl) phosphate (male: 13.2 mg/kg/day, female: 15.3 mg/kg/day). PMID:2636931

Kamata, E; Naito, K; Nakaji, Y; Ogawa, Y; Suzuki, S; Kaneko, T; Takada, K; Kurokawa, Y; Tobe, M

1989-01-01

98

The development of response surface pathway design to reduce animal numbers in toxicity studies  

PubMed Central

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. PMID:24661560

2014-01-01

99

Development of two animal models to study the function of Vibrio parahaemolyticus type III secretion systems.  

PubMed

Vibrio parahaemolyticus is an emerging food- and waterborne pathogen that encodes two type III secretion systems (T3SSs). Previous studies have linked type III secretion system 1 (T3SS1) to cytotoxicity and T3SS2 to intestinal fluid accumulation, but animal challenge models needed to study these phenomena are limited. In this study we evaluated the roles of the T3SSs during infection using two novel animal models: a model in which piglets were inoculated orogastrically and a model in which mice were inoculated in their lungs (intrapulmonarily). The bacterial strains employed in this study had equivalent growth rates and beta-hemolytic activity based on in vitro assays. Inoculation of 48-h-old conventional piglets with 10(11) CFU of the wild-type strain (NY-4) or T3SS1 deletion mutant strains resulted in acute, self-limiting diarrhea, whereas inoculation with a T3SS2 deletion mutant strain failed to produce any clinical symptoms. Intrapulmonary inoculation of C57BL/6 mice with the wild-type strain and T3SS2 deletion mutant strains (5 × 10(5) CFU) induced mortality or a moribund state within 12 h (80 to 100% mortality), whereas inoculation with a T3SS1 deletion mutant or a T3SS1 T3SS2 double deletion mutant produced no mortality. Bacteria were recovered from multiple organs regardless of the strain used in the mouse model, indicating that the mice were capable of clearing the lung infection in the absence of a functional T3SS1. Because all strains had a similar beta-hemolysin phenotype, we surmise that thermostable direct hemolysin (TDH) plays a limited role in these models. The two models introduced herein produce robust results and provide a means to determine how different T3SS1 and T3SS2 effector proteins contribute to pathogenesis of V. parahaemolyticus infection. PMID:20823199

Piñeyro, Pablo; Zhou, Xiaohui; Orfe, Lisa H; Friel, Patrick J; Lahmers, Kevin; Call, Douglas R

2010-11-01

100

INTRODUCTION Studies of animal developmental processes have typically  

E-print Network

. The legume/nitrogen-fixing bacteria symbiosis has been studied under laboratory con- ditions for over 100 in development, our knowledge of the influence of bacteria on plant development is comparatively sophisticated experimental system for the study of the influence of bacteria on animal development. Taking advantage

McFall-Ngai, Margaret

101

A Small Scale Experimental Study: Using Animations to Learn Vocabulary  

ERIC Educational Resources Information Center

This study attempts to investigate whether a difference exists between learning vocabulary via animation and via traditional paper-based method. This small scale study was conducted at Karadeniz Technical University in academic year 2009-2010. Two pre-intermediate classes were randomly selected as the experimental group (n = 17), and control group…

Kayaoglu, M. Naci; Dag Akbas, Raside; Ozturk, Zeynep

2011-01-01

102

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

2009-01-01

103

Pathogenicity of Pasteurella multiocida isolated from various animal sources for the domestic turkey and mice  

E-print Network

100 per cent. of the individual birds in the flock. Continuous preventive medication using currently available drugs has not proven to be effective. In 1969, more than 100 million turkeys were raised in the United States. It was estimated... of swine plague which is pathogenic for both mammals and birds. 5. P t 11 b~*t' P t 11 b 11' 2, f d domestic animals. The name Pssteurella multocida suggested by Rosenbusch and Merchant in 1939 (49) has found general acceptance in the North and South...

Villegas Narvaez, Pedro

1971-01-01

104

Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2?/??c?/? Mice?  

PubMed Central

The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells precludes virus infection in most mammalian species and limits the utility of small animal models for studies of disease pathogenesis, therapy, and vaccine development. One way to overcome this limitation is by human cell xenotransplantation in immune-deficient mice. However, this has proved inadequate, as engraftment of human immune cells is limited (both functionally and quantitatively) following transplantation of mature human lymphocytes or fetal thymus/liver. To this end, a human immune system was generated from umbilical cord blood-derived CD34+ hematopoietic stem cells in BALB/c-Rag2?/??c?/? mice. Intrapartum busulfan administration followed by irradiation of newborn pups resulted in uniform engraftment characterized by human T-cell development in thymus, B-cell maturation in bone marrow, lymph node development, immunoglobulin M (IgM)/IgG production, and humoral immune responses following ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor utilizing HIV-1ADA and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We conclude that humanized BALB/c-Rag2?/??c?/? mice represent a unique and valuable resource for HIV-1 pathobiology studies. PMID:17182671

Gorantla, Santhi; Sneller, Hannah; Walters, Lisa; Sharp, John G.; Pirruccello, Samuel J.; West, John T.; Wood, Charles; Dewhurst, Stephen; Gendelman, Howard E.; Poluektova, Larisa

2007-01-01

105

Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2-/-gammac-/- mice.  

PubMed

The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells precludes virus infection in most mammalian species and limits the utility of small animal models for studies of disease pathogenesis, therapy, and vaccine development. One way to overcome this limitation is by human cell xenotransplantation in immune-deficient mice. However, this has proved inadequate, as engraftment of human immune cells is limited (both functionally and quantitatively) following transplantation of mature human lymphocytes or fetal thymus/liver. To this end, a human immune system was generated from umbilical cord blood-derived CD34(+) hematopoietic stem cells in BALB/c-Rag2(-/-)gamma(c)(-/-) mice. Intrapartum busulfan administration followed by irradiation of newborn pups resulted in uniform engraftment characterized by human T-cell development in thymus, B-cell maturation in bone marrow, lymph node development, immunoglobulin M (IgM)/IgG production, and humoral immune responses following ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor utilizing HIV-1(ADA) and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We conclude that humanized BALB/c-Rag2(-/-)gamma(c)(-/-) mice represent a unique and valuable resource for HIV-1 pathobiology studies. PMID:17182671

Gorantla, Santhi; Sneller, Hannah; Walters, Lisa; Sharp, John G; Pirruccello, Samuel J; West, John T; Wood, Charles; Dewhurst, Stephen; Gendelman, Howard E; Poluektova, Larisa

2007-03-01

106

Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock?in mice, an animal model of autism spectrum disorders  

PubMed Central

Abstract Neuroligins are postsynaptic adhesion molecules that interacting with presynaptic neurexins ensure the cross?talk between pre? and postsynaptic specializations. Rare mutations in neurexin–neuroligin genes have been linked to autism spectrum disorders (ASDs). One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs. Animals carrying this mutation (NL3R451C knock?in mice) exhibit impaired social behaviors, reminiscent of those observed in ASD patients, associated with major alterations in both GABAergic and glutamatergic transmission, which vary among different brain regions and at different developmental stages. Here, pair recordings from parvalbumin? (PV) expressing basket cells and spiny neurons were used to study GABAergic synaptic signaling in layer IV barrel cortex of NL3R451C mutant mice. We found that the R451C mutation severely affects the probability of GABA release from PV?expressing basket cells, responsible for controlling via thalamo?cortical inputs the feed?forward inhibition. No changes in excitatory inputs to parvalbumin?positive basket cells or spiny neurons were detected. These data clearly show that primary targets of the NL3 mutation are PV?expressing basket cells, independently of the brain region where they are localized. Changes in the inhibitory gate of layer IV somatosensory cortex may alter sensory processing in ASD patients leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole. PMID:25347860

Cellot, Giada; Cherubini, Enrico

2014-01-01

107

Animal Ethics and the Scientific Study of Animals: Bridging the “Is” and the “Ought”  

Microsoft Academic Search

From ancient Greece to the present, philosophers have variously emphasized either the similarities or the differences between humans and nonhuman animals as a basis for ethical conclusions. Thus animal ethics has traditionally involved both factual claims, usually about animals’ mental states and capacities, and ethical claims about their moral standing. However, even in modern animal ethics the factual claims are

David Fraser; Rod Preece

2004-01-01

108

Study of the dynamic expression of Meis1 in mice  

PubMed Central

Background: Aggressive embryo and receptive endometrium are necessary for successful implantation. On this time endometrium transformates to receptive state, which permits embryonic implantation. Studies about embryonic implantation and endometrial receptivity are always a hot spot in the field of reproductive medicine. Objective: To investigate the expression pattern of Meis1 during peri-implantation in mice endometrium. Materials and Methods: Mice for experiment were raised in SPF environment. The mice were mated with a female/male ratio of 2:1. The female mice with detected plugs were regarded as pregnant day 1 (pd1). Endometrial tissues were collected respectively on pd1, pd2, pd4, pd5 and pd6. Immunohistochemistry was used to detect the location of Meis1 in mice endometrium. The expression level of mRNA and protein of Meis1 were further detected using Quantitative PCR and Western blotting, respectively. Results: We found that Meis1 is located in the cytoplasm and membrane of endometrial glandual epithelium cells and the nucleus of endometrial stromal and decidual cells. Both Quantitative RT-PCR and western blotting showed that Meis1 expressed regularly in mice endometrium. Meis1 mRNA expressed weakly on pd1, then significantly increased on pd4 (p=0.018), and achieved to a peak on pd5 (p=0.0012), it showed a decrease trend on pd6. Meis1 protein expressed weakly on pd1 and pd2, then significantly increased on pd4 and pd5 (p=0.0019), it showed a decrease trend on pd6 Conclusion: Meis1 is dynamically expressed in mice endometrium during peri-implantation. The time that Meis1 expression reaches its peak value is coincident with the implantation window, which implied that Meis1 is closely related with embryonic implantation. PMID:24639739

Hai-Xia, Li; Xin-Yu, Guo; Yan, Xie; Qi-Long, Yuan; Ming-Xiao, Ge; Jin-Yu, Zhang

2013-01-01

109

Oral Toxicity of Okadaic Acid in Mice: Study of Lethality, Organ Damage, Distribution and Effects on Detoxifying Gene Expression  

PubMed Central

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. PMID:24217398

Vieira, Andres C.; Rubiolo, Juan A.; López-Alonso, Henar; Cifuentes, José Manuel; Alfonso, Amparo; Bermúdez, Roberto; Otero, Paz; Vieytes, Mercedes R.; Vega, Félix V.; Botana, Luis M.

2013-01-01

110

Individual study of chromium in the stainless steel implants degradation: an experimental study in mice.  

PubMed

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 as controls. The levels of chromium found in the liver, kidney and spleen of the control and the treated animals were obtained by atomic absorption spectrometry (AAS) and were compared to those obtained by AdSV (adsorptive stripping voltammetry) to test the accuracy of the results. During the experimental period, the liver and spleen showed a progressive and significant accumulation of chromium whereas in the kidney the significant accumulation found after the first week practically remained unchanged during the four weeks. Apparently, the histological analysis of these tissues did not evidence any relevant morphological alteration induced by the chromium accumulations during the four weeks of treatment. PMID:10581692

Pereira, M do C; Pereira, M de L; Sousa, J P

1999-09-01

111

Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals  

PubMed Central

Objective To investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetula braunii, a plant used in ethnomedicine for the treatment of epilepsy. Methods The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks, pentylenetetrazole and 4-aminopyridine-induced seizures in mice. Results The preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins, carbohydrates, flavonoids, tannins, anthraquinones and steroids. Similarly, tannins, flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction. In the pharmacological screening, 150 mg/kg of the fraction protected 83.33% of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100% protection. In the 4-aminopyridine-induced seizure model, the fraction produced a significant (P<0.05) increase in the mean onset of seizure in unprotected animals. The fraction did not exhibit a significant activity against maximal electroshock convulsion. The median lethal dose of the fraction was found to be 1?261.91 mg/kg. Conclusions These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy. PMID:25182552

Aliyu, Musa Mumammad; Musa, Abdullahi Isma'il; Kamal, Muhammad Ja'afar; Mohammed, Magaji Garba

2014-01-01

112

Biocompatibility of electrochemically activated aqueous solutions: an animal study.  

PubMed

The purpose of the study was to evaluate the biocompatibility of electrochemically activated aqueous solutions on experimental animals. Nine rabbits were subjected to acute eye irritation/corrosion tests, nine rabbits to acute dermal irritation/corrosion and 30 rats to acute oral toxicity (LD50) tests. No significant negative effects were noted. Considering the relatively high levels of exposure of the animals to the solutions and the low levels in the anticipated real clinical situation it is argued that these solutions are indeed biocompatible. PMID:11901580

Marais, J T

2002-01-01

113

Why zoology? Zoology is the study of animals how they  

E-print Network

Why zoology? Zoology is the study of animals ­ how they function, behave and evolve. As well as being intrinsically fascinating, zoology is also of real- world importance. Understanding zoology for zoologists than today. Courses Essentials Courses MSci (Hons) in Zoology MSci (Hons) in Zoology (research

Sussex, University of

114

Study of different pinhole configurations for small animal tumor imaging  

Microsoft Academic Search

In this work, we design and study the properties of a novel geometric criteria-based multipinhole (MP) SPECT system, for imaging tumors and gene expression in small animals. The MP configuration was determined based on the following geometric criteria viz: 1) place the pinholes evenly in the vertical and horizontal directions of the collimator (so that a large number of axial

G. Bal; G. L. Zeng; R. M. Lewitt; Z. Cao; P. D. Acton

2004-01-01

115

Pain assessment in animal models: do we need further studies?  

PubMed Central

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. PMID:24855386

Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Viganò, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo

2014-01-01

116

Sepsis in Old Age: Review of Human and Animal Studies  

PubMed Central

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. PMID:24729938

Starr, Marlene E; Saito, Hiroshi

2014-01-01

117

[Animal experimentation, animal welfare and scientific research].  

PubMed

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

2013-10-01

118

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.

119

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

PubMed

Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion-repletion of hemoglobin is a method commonly used in animal studies. Three depletion-repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs. PMID:23790319

García, Y; Díaz-Castro, J

2013-10-01

120

Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations.  

PubMed

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. PMID:16039683

Dasenbrock, Clemens

2005-09-01

121

Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations  

SciTech Connect

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: clemens-dasebrock@bc.boehringer-ingelheim.com

2005-09-01

122

The use of transgenic animals to study lipoprotein metabolism  

SciTech Connect

The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

Rubin, E.M.; Plump, A.S.

1993-12-01

123

Quantitative in vivo analysis of small bowel motility using MRI examinations in mice - proof of concept study.  

PubMed

Small bowel motility analyses using magnetic resonance imaging (MRI) could reduce current invasive techniques in animal studies and comply with the 'three Rs' rule for human animal experimentation. Thus we investigated the feasibility of in vivo small bowel motility analyses in mice using dynamic MRI acquisitions. All experimental procedures were approved by the institutional animal care committee. Six C57BL/6 mice underwent MRI without additional preparation after isoflurane anaesthetization in the prone position on a 4.7 T small animal imager equipped with a linear polarized hydrogen birdcage whole-body mouse coil. Motility was assessed using a true fast imaging in a steady precession sequence in the coronal orientation (acquisition time per slice 512?ms, in-plane resolution 234?×?234?µm, matrix size 128?×?128, slice thickness 1?mm) over 30?s corresponding to 60 acquisitions. Motility was manually assessed measuring the small bowel diameter change over time. The resulting motility curves were analysed for the following parameters: contraction frequency per minute (cpm), maximal contraction amplitude (maximum to minimum [mm]), luminal diameter (mm) and luminal occlusion rate. Small bowel motility quantification was found to be possible in all animals with a mean small bowel contraction frequency of 10.67?cpm (SD?±?3.84), a mean amplitude of the contractions of 1.33?mm (SD?±?0.43) and a mean luminal diameter of 1.37?mm (SD?±?0.42). The mean luminal occlusion rate was 1.044 (SD?±?0.45%/100). The mean duration needed for a single motility assessment was 185?s (SD?±?54.02). Thus our study demonstrated the feasibility of an easy and time-sparing functional assessment for in vivo small bowel motility analyses in mice. This could improve the development of small animal models of intestinal diseases and provide a method similar to clinical MR examinations that is in concordance with the 'three Rs' for humane animal experimentation. PMID:25266965

Bickelhaupt, S; Wurnig, M C; Lesurtel, M; Patak, M A; Boss, A

2015-01-01

124

Resveratrol and diabetes: from animal to human studies.  

PubMed

Diabetes mellitus is a serious disease affecting about 5% of people worldwide. Diabetes is characterized by hyperglycemia and impairment in insulin secretion and/or action. Moreover, diabetes is associated with metabolic abnormalities and serious complications. Resveratrol is a natural, biologically active polyphenol present in different plant species and known to have numerous health-promoting effects in both animals and humans. Anti-diabetic action of resveratrol has been extensively studied in animal models and in diabetic humans. In animals with experimental diabetes, resveratrol has been demonstrated to induce beneficial effects that ameliorate diabetes. Resveratrol, among others, improves glucose homeostasis, decreases insulin resistance, protects pancreatic ?-cells, improves insulin secretion and ameliorates metabolic disorders. Effects induced by resveratrol are strongly related to the capability of this compound to increase expression/activity of AMPK and SIRT1 in various tissues of diabetic subjects. Moreover, anti-oxidant and anti-inflammatory effects of resveratrol were shown to be also involved in its action in diabetic animals. Preliminary clinical trials show that resveratrol is also effective in type 2 diabetic patients. Resveratrol may, among others, improve glycemic control and decrease insulin resistance. These results show that resveratrol holds great potential to treat diabetes and would be useful to support conventional therapy. This article is part of a Special Issue entitled: Resveratol: Challenges in translating pre-clincial findigns to iproved patient outcomes, guest edited by J. Dyck and P. Schrauwen. PMID:25445538

Szkudelski, Tomasz; Szkudelska, Katarzyna

2014-10-27

125

Histological and ultrastructural study of the inflammation evoked by Paracoccidioides brasiliensis antigen in previously immunized mice.  

PubMed

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

1989-01-01

126

Let There Be Light! Bioluminescent Imaging to Study Bacterial Pathogenesis in Live Animals and Plants.  

PubMed

: Bioluminescence imaging (BLI) of bacteria was primarily designed to permit real-time, sensitive, and noninvasive monitoring of the progression of infection in live animals. Generally, BLI relies on the construction of bacterial strains that possess the lux operon. The lux operon is composed of a set of genes that encode the luciferase enzyme and its cognate substrate, which interact to produce light-a phenomenon that is referred to as bioluminescence. Bioluminescence emitted by the bacteria can then be detected and imaged within a living host using sensitive charge-coupled device (CCD) cameras. In comparison to traditional host-pathogen studies, BLI offers the opportunity for extended monitoring of infected animals without resorting to euthanasia and extensive tissue processing at each time point. Therefore, BLI can reduce the number of animals required to generate meaningful data, while significantly contributing to the understanding of pathogenesis in the host and, subsequently, the development and evaluation of adequate vaccines and therapeutics. BLI is also useful in characterizing the interactions of pathogens with plants and the para-host environment. In this chapter, we demonstrate the broad application of BLI for studying bacterial pathogens in different niches. Furthermore, we will specifically focus on the use of BLI to characterize the following: (1) the pathogenesis of Brucella melitensis in mice (animal host), and (2) the progression of infection of Clavibacter michiganensis subsp. michiganensis in tomatoes (plant host). These studies will provide an overview of the wide potential of BLI and its role in enhancing the study of unique-and sometimes difficult-to-characterize-bacterial pathogens. PMID:25395174

Kassem, Issmat I; Splitter, Gary A; Miller, Sally; Rajashekara, Gireesh

2014-11-14

127

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

SciTech Connect

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

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

1994-05-01

128

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.

1990-01-01

129

Significance of ecological studies of wild animal reservoirs of zoonoses  

PubMed Central

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. PMID:13791420

Abdussalam, M.

1959-01-01

130

Inhalation developmental toxicology studies: Gallium arsenide in mice and rats  

SciTech Connect

Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

1990-12-01

131

Painful dilemmas: A study of the way the public's assessment of animal research balances costs to animals against human benefits.  

PubMed

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 Bøker; Mørkbak, Morten Raun; Lassen, Jesper; Sandøe, Peter

2014-05-01

132

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.

133

A comparative study of coagulation systems in newborn animals.  

PubMed

Appropriate animal experimentation can enhance our understanding of thrombotic and hemorrhagic problems in the human neonate. Which newborn animal species' coagulation system most closely resembles the human neonate is unknown. The objective of the study was to assess the newborn coagulation system in four animal species and compare them with the human neonate. Blood samples were drawn on days 1 and 7 of life from lambs (n = 10), piglets, (n = 12), rabbit pups (n = 12), and beagle pups (n = 7). Coagulation screening tests, specific factor assays, and specific inhibitors of the coagulation system were measured. All factor assays were expressed as a percent of the respective species pooled adult plasma. The results from the animals were compared to normal values from our laboratory for healthy full-term infants. The coagulation systems of all species tested, except the rabbit pup, were immature at birth with most factor levels being lower than the adult of their species. The coagulation systems were influenced by the postnatal age of the animal and the factor levels reached adult values in fewer days relative to the human. The coagulation system for the piglet most closely approximated the human neonate. The shared characteristics were prolonged screening tests, increased factor VIII:C, generally low levels for the contact and vitamin K-dependent factors, and low antithrombin III levels relative to the adult. The beagle pup also showed many similar characteristics but in contrast to the human neonate factor VIII:C and V were low on day 1 of life and prekallikrein was not measurable in the adult or newborn beagle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3774411

Massicotte, P; Mitchell, L; Andrew, M

1986-10-01

134

Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models  

PubMed Central

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. PMID:19578526

Jain, Mohit Raja; Ge, Wei-wen; Elkabes, Stella; Li, Hong

2009-01-01

135

Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model.  

PubMed

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Yeap, Swee Keong; Abdul Samad, Nozlena; Andas, Reena Joys; Muhammad Nadzri, Nabilah; Anasamy, Theebaa; Ng, Kuan Beng; How, Chee Wun

2014-01-01

136

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model  

PubMed Central

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200?mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200?mg/kg, thus, safe by oral administration. PMID:25276798

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

2014-01-01

137

The Effect of S-Adenosylmethionine on Cognitive Performance in Mice: An Animal Model Meta-Analysis  

PubMed Central

Background Alzheimer's disease (AD) is the most frequently diagnosed form of dementia resulting in cognitive impairment. Many AD mouse studies, using the methyl donor S-adenosylmethionine (SAM), report improved cognitive ability, but conflicting results between and within studies currently exist. To address this, we conducted a meta-analysis to evaluate the effect of SAM on cognitive ability as measured by Y maze performance. As supporting evidence, we include further discussion of improvements in cognitive ability, by SAM, as measured by the Morris water maze (MWM). Methods We conducted a comprehensive literature review up to April 2014 based on searches querying MEDLINE, EMBASE, Web of Science, the Cochrane Library and Proquest Theses and Dissertation databases. We identified three studies containing a total of 12 experiments that met our inclusion criteria and one study for qualitative review. The data from these studies were used to evaluate the effect of SAM on cognitive performance according to two scenarios: 1. SAM supplemented folate deficient (SFD) diet compared to a folate deficient (FD) diet and 2. SFD diet compared to a nutrient complete (NC) diet. Hedge's g was used to calculate effect sizes and mixed effects model meta-regression was used to evaluate moderating factors. Results Our findings showed that the SFD diet was associated with improvements in cognitive performance. SFD diet mice also had superior cognitive performance compared to mice on an NC diet. Further to this, meta-regression analyses indicated a significant positive effect of study quality score and treatment duration on the effect size estimate for both the FD vs SFD analysis and the SFD vs NC analysis. Conclusion The findings of this meta-analysis demonstrate efficacy of SAM in acting as a cognitive performance-enhancing agent. As a corollary, SAM may be useful in improving spatial memory in patients suffering from many dementia forms including AD. PMID:25347725

Montgomery, Sarah E.; Sepehry, Amir A.; Wangsgaard, John D.; Koenig, Jeremy E.

2014-01-01

138

Animal models for the mechanistic study of systemic lymphangiomatosis.  

PubMed

The systematic study of focused animal models has produced an explosion of information regarding the mechanisms governing lymphatic development and the diseases associated with lymphatic dysfunction. Nevertheless, the pathogenesis of systemic lymphangiomatosis has, thus far, eluded mechanistic comprehension. In this review, recent molecular advances in lymphatic vascular development are considered within the context of the animal models that have produced evolving insights. The emerging role of the zebrafish within lymphatic investigation is discussed. Specific models of the human disease pathology are considered in detail. While much has been learned about the molecular framework that surrounds normal lymphatic vascular development, the defect responsible for systemic lymphangiomatosis remains elusive. Development of more robust, recapitulative models will also be invaluable to investigate new and emerging therapeutics for the often devastating disease of systemic lymphangiomatosis. PMID:22196285

Rockson, Stanley G

2011-01-01

139

The need for juvenile animal studies--a critical review.  

PubMed

With the introduction of specific pediatric legislation in the United States (US) and the European Union (EU) requiring the development of medicines for children the interest in juvenile animal studies (JAS) increased, but also the discussion about the value and necessity of such studies. Regulatory guidance regarding JAS is available from The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) M3(R2) guideline and from more specific guidance documents issued by the Food and Drug Administration (FDA) as well as the European Medicines Agency (EMA). This paper summarizes and discusses the regulatory requirements regarding the need for JAS, their design and timing as well as the current experience with such studies. The relevant guidance documents as well as several authors support a case-by-case approach regarding the need for and design of JAS. JAS should be considered, especially in cases when organ systems undergoing postnatal development, like the kidney, the skeleton or the central nervous system (CNS), have been identified as toxicity target organs, as developing organ systems usually are more sensitive to toxicity than mature organs. The relevance of the findings from JAS for human use will essentially depend on an appropriate study design, especially on the choice of species as well as the age of the juvenile animal at the start of study. As the available data from JAS show, the design of JAS seems to have improved since the introduction of specific guidance documents. However, so far, there is not enough experience to finally answer the question if JAS are useful. Interpretation of the results from JAS and their extrapolation to the pediatric population is hampered by the incomplete understanding of the animal models used in these studies as well as the lack of access to existing JAS data. Further data will be necessary to ultimately clarify the need for such studies. PMID:23108189

Soellner, Liane; Olejniczak, Klaus

2013-02-01

140

Carcinogenesis Studies of Cresols in Rats and Mice  

PubMed Central

Cresols, monomethyl derivatives of phenol, are high production chemicals with potential for human exposure. The three isomeric forms of cresol are used individually or in mixtures as disinfectants, preservatives, and solvents or as intermediates in the production of antioxidants, fragrances, herbicides, insecticides, dyes, and explosives. Carcinogenesis studies were conducted in groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40 mixture of m and p cresols (m-/p-cresol) in feed. Rats and mice were fed diets containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm, respectively. Survival of each exposed group was similar to that of their respective control group. Mean body weight gains were depressed in rats exposed to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over that of controls for the final mean body weight in mice exposed to 10,000 ppm appeared to be associated with lack of palatability of the feed. A marginally increased incidence of renal tubule adenoma was observed in the 15,000 ppm-exposed rats. The increased incidence was not statistically significant, but did exceed the range of historical controls. No increased incidence of hyperplasia of the renal tubules was observed; however, a significantly increased incidence of hyperplasia of the transitional epithelium associated with an increased incidence of nephropathy was observed at the high exposure concentration. The only significantly increased incidence of a neoplastic lesion related to cresol exposure observed in these studies was that of squamous cell papilloma in the forestomach of 10,000 ppm-exposed mice. A definitive association with irritation at the site-of-contact could not be made because of limited evidence of injury to the gastric mucosa at the time of necropsy. However, given the minimal chemical-related neoplastic response in these studies, it was concluded that there was no clear evidence of carcinogenicity in male rats or female mice exposed to the cresol mixture. PMID:19114085

Sanders, J.M.; Bucher, J.R.; Peckham, J.C.; Kissling, G.E.; Hejtmancik, M.R.; Chhabra, R.S.

2010-01-01

141

Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis.  

PubMed Central

Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder primarily involving motoneurons. A subset of individuals with familial autosomal dominant forms of the disease have mutations of the copper/zinc superoxide dismutase (Cu/Zn SOD, SOD-1) gene, which encodes a ubiquitously expressed enzyme that plays a key role in oxygen free radical scavenging. This observation suggests that altered or reduced SOD-1 activity may play a role in the neurodegenerative process. To explore this possibility further, we have introduced a mutation into the mouse SOD-1 gene that corresponds to one of the changes found in the human gene in familial amyotrophic lateral sclerosis. Integration and expression of this mouse gene in transgenic mice was identified by the presence of a unique restriction enzyme site in the transgene coding sequence generated by introduction of the mutation. We report here that high expression of this altered gene in the central nervous systems of transgenic mice is associated with an age-related rapidly progressive decline of motor function accompanied by degenerative changes of motoneurons within the spinal cord, brain stem, and neocortex. These findings indicate a causative relationship between altered SOD activity and motoneuron degeneration. Moreover, biochemical studies indicate normal levels of total SOD activity in transgenic mouse tissues, results that indicate that the neurodegenerative disorder does not result from a diminution of activity and, as such, represents a dominant "gain of function" mutation. Images Fig. 1 Fig. 2 PMID:7846037

Ripps, M E; Huntley, G W; Hof, P R; Morrison, J H; Gordon, J W

1995-01-01

142

Tumor radiosensitization with concomitant bone marrow radioprotection: a study in mice using diethyldithiocarbamate (DDC) under oxygenated and hypoxic conditions  

SciTech Connect

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.

1985-06-01

143

Using Computational and Mechanical Models to Study Animal Locomotion  

PubMed Central

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

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

2012-01-01

144

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

145

Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities  

PubMed Central

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. PMID:21829300

Guruprasad, K. P.; Mascarenhas, Roshan; Gopinath, P. M.; Satyamoorthy, K.

2010-01-01

146

Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy  

PubMed Central

Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies. PMID:21785565

Zucconi, Eder; Vieira, Natassia Moreira; Bueno, Carlos Roberto; Secco, Mariane; Jazedje, Tatiana; Costa Valadares, Marcos; Fussae Suzuki, Miriam; Bartolini, Paolo; Vainzof, Mariz; Zatz, Mayana

2011-01-01

147

Study in Mice Links Key Signaling Molecule to Underlying Cause of Osteogenesis Imperfecta  

MedlinePLUS

Spotlight on Research 2014 August 2014 Study in Mice Links Key Signaling Molecule to Underlying Cause of ... genetic disease characterized by fragile bones. Working in mice, the researchers found that TGF-?, a molecule ...

148

Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model.  

PubMed

Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective. PMID:24194717

Cheng, Xiao-Rui; Cui, Xiu-Liang; Zheng, Yue; Zhang, Gui-Rong; Li, Peng; Huang, Huang; Zhao, Yue-Ying; Bo, Xiao-Chen; Wang, Sheng-Qi; Zhou, Wen-Xia; Zhang, Yong-Xiang

2013-01-01

149

Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model  

PubMed Central

Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective. PMID:24194717

Cheng, Xiao-rui; Cui, Xiu-liang; Zheng, Yue; Zhang, Gui-rong; Li, Peng; Huang, Huang; Zhao, Yue-ying; Bo, Xiao-chen; Wang, Sheng-qi; Zhou, Wen-xia; Zhang, Yong-xiang

2013-01-01

150

Effects of developmental bisphenol A exposure on reproductive-related behaviors in California mice (Peromyscus californicus): a monogamous animal model.  

PubMed

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. PMID:23405200

Williams, Scott A; Jasarevic, Eldin; Vandas, Gregory M; Warzak, Denise A; Geary, David C; Ellersieck, Mark R; Roberts, R Michael; Rosenfeld, Cheryl S

2013-01-01

151

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

2014-03-01

152

Using animal models to study post-partum psychiatric disorders.  

PubMed

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. PMID:24527704

Perani, C V; Slattery, D A

2014-10-01

153

Role of human- and animal-sperm studies in the evaluation of male reproductive hazards  

SciTech Connect

Human sperm tests provide a direct means of assessing chemically induced spermatogenic dysfunction in man. Available tests include sperm count, motility, morphology (seminal cytology), and Y-body analyses. Over 70 different human exposures have been monitored in various groups of exposed men. The majority of exposures studied showed a significant change from control in one or more sperm tests. When carefully controlled, the sperm morphology test is statistically the most sensitive of these human sperm tests. Several sperm tests have been developed in nonhuman mammals for the study of chemical spermatotoxins. The sperm morphology test in mice has been the most widely used. Results with this test seem to be related to germ-cell mutagenicity. In general, animal sperm tests should play an important role in the identification and assessment of potential human reproductive hazards. Exposure to spermatotoxins may lead to infertility, and more importantly, to heritable genetic damage. While there are considerable animal and human data suggesting that sperm tests may be used to detect agents causing infertility, the extent to which these tests detect heritable genetic damage remains unclear. (ERB)

Wyrobek, A.J.; Gordon, L.; Watchmaker, G.

1982-04-07

154

Imaging Primary Lung Cancers in Mice to Study Radiation Biology  

SciTech Connect

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: david.kirsch@duke.ed [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)

2010-03-15

155

A 13-week subchronic intravaginal toxicity study of pokeweed antiviral protein in mice.  

PubMed

Pokeweed antiviral protein (PAP), a 29-kDa plant-derived protein isolated from Phytolacca americana, is a broad-spectrum antiviral agent. PAP shows unique clinical potential to become the active ingredient of a non-spermicidal microbicide because of its potent in vivo anti-HIV activity, non-interference with in vivo sperm functions, and lack of cytotoxicity to genital tract epithelial cells. Over 13 weeks the subchronic and reproductive toxicity potential of an intravaginally administered gel formulation of PAP was studied in mice to support its further development as a vaginal microbicide. Female B6C3F1 and CD-1 mice in subgroups of 20, were exposed intravaginally to a gel formulation containing 0, 0.025, 0.05, or 0.1% PAP, 5 days/week for 13 consecutive weeks. On a molar basis, these concentrations are 500- to 2000-times higher than the in vitro anti-HIV IC50 value. After 13 weeks of intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, and absolute and relative organ weights. Blood was analyzed for hematology and clinical chemistry profiles. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Placebo-control and PAP-dosed female CD-1 mice were mated with untreated males in order to evaluate if PAP has any deleterious effects on reproductive performance. There were no treatment-related mortalities. Mean body weight gain was not reduced by PAP treatment during the dosing period. The hemogram and blood chemistry profiles revealed lack of systemic toxicity following daily intravaginal instillation of PAP for 13 weeks. No clinically significant changes in absolute and relative organ weights were noted in the PAP dose groups. Extensive histopathological examination of tissues showed no increase in treatment-related microscopic lesions in any of the three PAP dose groups. Repeated intravaginal exposure of CD-1 mice to increasing concentrations of PAP for 13 weeks showed no adverse effect on their subsequent reproductive capability (100% fertile), neonatal survival (>90%) or pup development. Collectively, these findings demonstrate that repetitive intravaginal administration of PAP at concentrations as high as 2000 times its in vitro anti-HIV IC50 value was not associated with local or systemic toxicity and did not adversely affect the reproductive performance of mice. PAP may be useful as an active ingredient of a safe vaginal microbicide for prevention of the sexual transmission of viruses, particularly of HIV-1. PMID:15185849

D'Cruz, O J; Waurzyniakt, B; Uckun, F M

2004-01-01

156

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)  

PubMed Central

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

157

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.

1999-11-01

158

A Video Data Base System for Studying Animal Behavior1,2  

Microsoft Academic Search

Classification of farm animal be- havior is based on oral or written descriptions of the activity in which the animal is engaged. The quantifi- cation of animal behavior for research requires that individuals recognize and code the behavior of the animal under study. The classification of these be- haviors can be subjective and may differ among observers. Illustrated guides to

J. Morrow-Tesch; J. W. Dailey; H. Jiang

2010-01-01

159

Functional Changes in Neocortical Activity in Huntington's Disease Model Mice: An in vivo Intracellular Study  

PubMed Central

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. PMID:21720524

Stern, Edward A.

2011-01-01

160

Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study  

SciTech Connect

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: gangsg@radiol.snu.ac.kr; 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)

2006-10-15

161

AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors.  

PubMed

Transcription factors (TFs) are key regulators for gene expression. Here we updated the animal TF database AnimalTFDB to version 2.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/). Using the improved prediction pipeline, we identified 72 336 TF genes, 21 053 transcription co-factor genes and 6502 chromatin remodeling factor genes from 65 species covering main animal lineages. Besides the abundant annotations (basic information, gene model, protein functional domain, gene ontology, pathway, protein interaction, ortholog and paralog, etc.) in the previous version, we made several new features and functions in the updated version. These new features are: (i) gene expression from RNA-Seq for nine model species, (ii) gene phenotype information, (iii) multiple sequence alignment of TF DNA-binding domains, and the weblogo and phylogenetic tree based on the alignment, (iv) a TF prediction server to identify new TFs from input sequences and (v) a BLAST server to search against TFs in AnimalTFDB. A new nice web interface was designed for AnimalTFDB 2.0 allowing users to browse and search all data in the database. We aim to maintain the AnimalTFDB as a solid resource for TF identification and studies of transcription regulation and comparative genomics. PMID:25262351

Zhang, Hong-Mei; Liu, Teng; Liu, Chun-Jie; Song, Shuangyang; Zhang, Xiantong; Liu, Wei; Jia, Haibo; Xue, Yu; Guo, An-Yuan

2015-01-28

162

In vivo study of endometriosis in mice by photoacoustic microscopy.  

PubMed

Endometriosis (EM) impacts the healthcare and the quality of life for women of reproductive age. However, there is no reliable noninvasive diagnosis method for either animal study or clinical use. In this work, a novel imaging method, photoacoustic microscopy (PAM) was employed to study the EM on the mouse model. Our results demonstrated the PAM noninvasively provided the high contrast and 3D imaging of subcutaneously implanted EM tissue in the nude mouse in vivo. The statistical study also indicated PAM had high sensitivity and specificity in the diagnosis of EM in this animal study. In addition, we also discussed the potential clinical application for PAM in the diagnosis of EM. (© 2014 WILEY-VCH Verlag GmbH &Co. KGaA, Weinheim). PMID:24519971

Ding, Yichen; Zhang, Mingzhu; Lang, Jinghe; Leng, Jinhua; Ren, Qiushi; Yang, Jie; Li, Changhui

2015-01-01

163

Choosing the Correct AED: From Animal Studies to the Clinic  

PubMed Central

Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy has been directed primarily toward reducing excitability through blockage of voltage-gated Na+ or Ca2+ channels, or increasing inhibition through enhancement of ?-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals, usually rodents. Maximal electrical shock, pentylenetetrazol, and kindling are typically used as non-mechanistic screens for antiseizure properties and the rotorod test for assessing acute toxicity. While antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it should be emphasized that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than adults. Despite these age-related unique features, drugs used in children are generally the same as used in adults. As awareness of the unique features of seizures during development increases, it is anticipated that more drug screening in the immature animal will occur. PMID:18279749

Holmes, Gregory L.; Zhao, Qian

2009-01-01

164

[Stapotomy with ultrasound? Animal experiment study of possible side effects].  

PubMed

Stapedectomy by ultrasound has been proposed as an alternative method for perforating the stapes footplate in surgery for otosclerosis. Possible functional adverse effects of ultrasound perforation of the otic capsule in guinea pigs were investigated in the present study by means of vestibular evoked potentials (VsEP). VsEP were elicited by pulsed linear accelerations applied to the animal's head following surgical removal of the middle ear, following intense ultrasound drilling around the otic capsule and after drilling a small hole in the anterior bony wall of the vestibule. All manipulations did not affect amplitudes and latencies of the early potential N1 (less than 1 msec after onset of acceleration). Significant alterations of N1 occurred following direct mechanical damage of the otolithic organs, indicating that VsEP can be used to detect lesions of these receptors and therefore may be used as a parameter of vestibular function in experimental animals. Findings indicate that perforation of the otic capsule by ultrasound is possible without inducing functional lesions of the otolithic organs. PMID:8125798

Böhmer, A

1993-12-01

165

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

2009-03-01

166

Interleukin 1 protects against the lethal effects of irradiation of mice but has no effect on tumors in the same animals.  

PubMed

Interleukin 1 (IL-1) is a radioprotector of bone marrow and is cytotoxic to some tumor cells. This investigation examines these two properties in the same host animals and gives evidence of radioprotection against localized x-irradiation of the head and neck region. By LD50 analyses, recombinant human IL-1 (100 ng/mouse, approximately 3 micrograms/kg) was found to be radioprotective against whole-body irradiation for both C3H/Km and C57BL/Ka mice. The combined potency ratio for the two strains was 1.07 (95% confidence limit: 1.02-1.12). It was also radioprotective against the injury leading to acute lethality resulting from localized head and neck irradiation of C3H/Km mice; 100 ng of IL-1/mouse produced a potency ratio of 1.05 (95 confidence limit: 1.03-1.07). However, two tumors that originated in C3H/Km mice, RIF-1 and SCCVII, showed neither in vitro nor in vivo response to IL-1. Also, there was no IL-1-induced reduction in in vivo growth of the RL 12NP lymphoma in C57BL/Ka mice. PMID:2654945

Dorie, M J; Allison, A C; Zaghloul, M S; Kallman, R F

1989-05-01

167

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals  

PubMed Central

Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-? (TGF-?) isoforms and their receptors, as well as factors secondary to TGF-? action. Additionally, these studies determined that TGF-? and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway. PMID:16809921

Sarkar, Dipak K.

2010-01-01

168

Inhalation reproductive toxicology studies: Sperm morphology study of n-hexane in B6C3F1 mice: Final report  

SciTech Connect

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate the epididymal sperm morphology of male B6D3F1 mice 5 weeks after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Two concurrent positive control groups of animals were injected intraperitoneally with either 200 or 250 mg/kg ethyl methanesulfonate, a known mutagen, once each day for 5 consecutive days. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. During the fifth post-exposure week the animals were killed and examined for gross lesions of the reproductive tract and suspensions of the epididymal sperm were prepared for morphological evaluations. The appearance and behavior of the mice were unremarkable throughout the experiment and there were no deaths. No evidence of lesions in any organ was noted at sacrifice. Mean body weights of male mice exposed to n-hexane were not significantly different from those for the 0-ppM animals at any time during the study. Analyses of the sperm morphology data obtained 5 weeks post-exposure (the only time point examined) indicated that exposure of male mice to relatively high concentrations of n-hexane vapor for 5 days produced no significant effects on the morphology of sperm relative to that of the 0-ppM control group. 24 refs., 2 figs., 7 tabs.

Mast, T.J.; Hackett, P.L.; Decker, J.R.; Westerberg, R.B.; Sasser, L.B.; McClanahan, B.J.; Rommereim, R.L.; Evanoff, J.J.

1988-08-01

169

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.

1981-01-01

170

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 (;)

2005-06-01

171

Guideline Regarding Significant Changes to Animal Study Proposals The Animal Welfare Regulations and the PHS Policy on Humane Care and Use of Laboratory  

E-print Network

and the PHS Policy on Humane Care and Use of Laboratory Animals (PHS Policy) require that Animal Care and Use described in an ACUC approved Animal Study Proposal (ASP). The NIH interprets significant changes to mean their responsibilities regarding changes in approved ASPs, the NIH Animal Research Advisory Committee (ARAC) offers

Bandettini, Peter A.

172

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.

2010-12-23

173

Fertility of female mice fed coumestrol and diethylstilbestrol  

Microsoft Academic Search

Coumestrol, a compound produced by various legumes which exerts estrogen?like activity in animals, and diethylstilbestrol (DES) were studied as chemical agents for controlling reproduction in mice. Female mice were fed control diets or diets containing 100 ppm coumestrol for eight days. Female mice were exposed to males and reproductive tracts examined 14 days later. Litter size was not affected by

Elias A. Elias; R. L. Kincaid

1984-01-01

174

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.

1989-01-01

175

Behavioural Trajectories of Adaptive Mobile Robot for Animal Behaviour Studies  

Microsoft Academic Search

Modelling animal behaviour using adaptive mobile robots is a well stabilised methodology that permits to test, in an extremely controlled setting, hypnotises, constrains and assumptions about how organisms orient themselves. We apply this methodology to simulate experiments with rats in open field box. Animal psychologists have used open field box settings in order to empirically show the formal structure of

Orazio Miglino; Henrik Hautop Lund

2001-01-01

176

Animal models for the study of intestinal lymphatic drug transport  

Microsoft Academic Search

Drug transport via the intestinal lymphatic system has been shown to contribute to the absorption of a number of orally administered highly lipophilic drugs. In order to investigate this phenomenon and assist in the development of improved oral formulations, the use of appropriate animal models is required. This paper reviews the use of various animal models for this purpose, and

Glenn A Edwards; Christopher J. H Porter; Suzanne M Caliph; Shui-Mei Khoo; W. N Charman

2001-01-01

177

In Vivo Toxicity Studies of Europium Hydroxide Nanorods in Mice  

PubMed Central

Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence properties and pro-angiogenic to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [EuIII(OH)3] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mgKg?1day?1) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice sacrificed on day 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods. PMID:19616569

Patra, Chitta Ranjan; Abdel Moneim, Soha S.; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

2009-01-01

178

Copyright: Potts & White, May 2007 New Zealand Centre for Human-Animal Studies  

E-print Network

Copyright: Potts & White, May 2007 New Zealand Centre for Human-Animal Studies Cruelty-Director: New Zealand Centre for Human-Animal Studies Te Whare Wananga o Waitaha/University of Canterbury Overview 14 Participants (according to gender & status as `NZ born' or `tauiwi') 14 Status of animal

Hickman, Mark

179

Bridging human and animal research: A comparative approach to studies of personality and health  

Microsoft Academic Search

This article evaluates a comparative approach to personality and health research. We (1) review evidence showing that personality exists and can be measured in animals, (2) illustrate the benefits of animal studies for human personality research, (3) illustrate the benefits of human studies for animal personality research, and (4) provide guidelines for making cross-species comparisons. We conclude that a comparative

Pranjal H. Mehta; Samuel D. Gosling

2008-01-01

180

Dosimetry for Small Animal Studies Radiation Medicine Program, Princess Margaret Hospital  

E-print Network

· Monte Carlo studies #12;Small Animal Irradiation Experiments Whole Body Gammacell 40 (Best TheratronicsDosimetry for Small Animal Studies Radiation Medicine Program, Princess Margaret Hospital (Livia Garzia) · Robert Weersink #12;Outline · Systems for small animal irradiation · Image

181

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

PubMed

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

2007-07-01

182

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  

SciTech Connect

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.

1980-01-01

183

Genetic and ecological studies of animals in Chernobyl and Fukushima.  

PubMed

Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. PMID:25124815

Mousseau, Timothy A; Møller, Anders P

2014-01-01

184

PILOT STUDY FOR ARSENIC CARCINOGENESIS IN P53 HETEROZYGOTE DEFICIENT MICE  

EPA Science Inventory

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...

185

The use of on-animal acoustical recording devices for studying animal behavior  

PubMed Central

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

2013-01-01

186

The use of on-animal acoustical recording devices for studying animal behavior.  

PubMed

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

2013-07-01

187

Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis  

PubMed Central

Background: Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. Methods: The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. Results: The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. Conclusion: The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations. PMID:25246833

ALVAREZ, Nadine; INFANTE, Juan Francisco; BORRERO, Reinier; MATA, Dulce; PAYAN, JORGE BARRIOS-; HOSSAIN, Md. Murad; MOHD NOR, Norazmi; SARMIENTO, María Elena; HERNANDEZ-PANDO, Rogelio; ACOSTA, Armando

2014-01-01

188

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.

1975-01-01

189

Cigarette smoke impairs granulosa cell proliferation and oocyte growth after exposure cessation in young Swiss mice: an experimental study  

PubMed Central

Background Cigarette smoke is associated with decreased female fertility, causing damage to ovarian function and disturbing follicle development. However, the effects of cigarette toxicants on ovarian function depend on duration and intensity of exposure. The aim of this study was to assess the effects of brief, intense exposure to tobacco smoke on granulosa cell number, oocyte growth, and follicle size during puberty in female Swiss mice. Methods Ten female Swiss mice aged 35 days were exposed to tobacco smoke from 3R4F reference research cigarettes. They were exposed to an automatic smoking machine 8 h/day, 7 days/week for 15 days. Ten age-matched controls were kept in a different room and exposed to ambient air. At the end of 15 days, five mice in each group were euthanized and the ovaries were analyzed for follicular morphometry and granulosa cell count. The remaining animals were kept for an additional 30 days for further analysis as an ex-smoker group and control group. Comparison between the two groups was evaluated by the Student’s t-test or a two-way ANOVA followed by Bonferroni post-test was applied for multiple comparisons. Results We found that cigarette smoke impaired antral follicular growth even after exposure cessation (p < 0.001). Both smoking and ex-smoking groups exhibited similar follicle diameter. However, at the same follicular stage, the number of granulosa cells was smaller in the ex-smoking group compared to smoking animals (p < 0.001). This was associated with increased oocyte diameter in ex-smoking animals compared to smoking animals (p < 0.01). Conclusions The negative effects of cigarette smoking seem to last even after exposure has been interrupted. Moreover, brief exposure during puberty may induce silent oocyte disruption, which could in turn lead to decreased fecundity rates. PMID:22995067

2012-01-01

190

Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare  

PubMed Central

In research aimed at improving human health care, animal studies still play a crucial role, despite political and scientific efforts to reduce preclinical experimentation in laboratory animals. In animal studies, the results and their interpretation are not always straightforward, as no single study is executed perfectly in all steps. There are several possible sources of bias, and many animal studies are replicates of studies conducted previously. Use of meta-analysis to combine the results of studies may lead to more reliable conclusions and a reduction of unnecessary duplication of animal studies. In addition, due to the more exploratory nature of animal studies as compared to clinical trials, meta-analyses of animal studies have greater potential in exploring possible sources of heterogeneity. There is an abundance of literature on how to perform meta-analyses on clinical data. Animal studies, however, differ from clinical studies in some aspects, such as the diversity of animal species studied, experimental design, and study characteristics. In this paper, we will discuss the main principles and practices for meta-analyses of experimental animal studies. PMID:25541544

Hooijmans, Carlijn R.; IntHout, Joanna; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.

2014-01-01

191

Haemolysis and Perturbations in the Systemic Iron Metabolism of Suckling, Copper-Deficient Mosaic Mutant Mice – An Animal Model of Menkes Disease  

PubMed Central

The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism. PMID:25247420

Lenartowicz, Ma?gorzata; Starzy?ski, Rafa? R.; Krzeptowski, Wojciech; Grzmil, Pawe?; Bednarz, Aleksandra; Ogórek, Mateusz; Pierzcha?a, Olga; Staro?, Robert; Gajowiak, Anna; Lipi?ski, Pawe?

2014-01-01

192

Studies on the toxicity of biuret to animals  

E-print Network

Agrioultural Experiment Station. The author expresses his sincere appreciation to the follosingX Dr. H. 0. Kunkel, Associate Professor, Biochemistry and Mutrition and Animal Husbandry, fox his guidance and super vision in planning the proJect, interpreting... the data, and prepaxation of the manuscxipt, J. K. Higgs, Professor of Animal Husbandry, fox' his advice and suggestions in planning end executing the pro]ect and in preparation of the theology Dx ~ R Ro Shrodey Associate Professox of Oenetice...

Berry, William T

2012-06-07

193

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

PubMed Central

Background: Oxidative stress plays a major role in the pathogenesis of chronic fatigue syndrome (CFS). Keeping in view the proven antioxidant activity of Triticum aestivum L., this study has been undertaken to explore the potential therapeutic benefit of this plant in the treatment of CFS. Objective: To study the protective effect of the ethanolic extract of the leaves of Triticum aestivum (EETA) in an experimental mice model of CFS. Materials and Methods: Five groups of albino mice (20-25 g) were selected for the study, with five animals in each group. Group A served as the naïve control and Group B served as the stressed control. Groups C and D received EETA (100 mg/kg and 200 mg/kg b.w.). Group E received imipramine (20 mg/kg b.w.). Except for Group A, mice in each group were forced to swim 6 min each for 7 days to induce a state of chronic fatigue. Duration of immobility was measured on every alternate day. After 7 days, various behavioral tests (mirror chamber and elevated plus maize test for anxiety, open field test for locomotor activity) and biochemical estimations (malondialdehyde [MDA] and catalase activity) in mice brain were performed. Results: Forced swimming in the stressed group resulted in a significant increase in immobility period, decrease in locomotor activity and elevated anxiety level. The brain homogenate showed significantly increased MDA and decreased catalase levels. The extract-treated groups showed significantly (P < 0.05) improved locomotor activity, decreased anxiety level, elevated catalase levels and reduction of MDA. Conclusion: The study confirms the protective effects of EETA in CFS. PMID:25276064

Borah, Mukundam; Sarma, Phulen; Das, Swarnamoni

2014-01-01

194

Feasibility study of voice-driven data collection in animal drug toxicology studies.  

PubMed

The object of this study was to determine the feasibility of using voice recognition technology to enable hands-free and eyes-free collection of data related to animal drug toxicology studies. Specifically, we developed and tested a prototype voice-driven data collection system for histopathology data using only voice input and computer-generated voice responses. The overall accuracy rate was 97%. Additional work is needed to minimize training requirements and improve audible feedback. We conclude that this architecture could be considered a viable alternative for data collection in animal drug toxicology studies with reasonable recognition accuracy. PMID:7531129

Grasso, M A; Grasso, C T

1994-07-01

195

Guidelines for the ethical use of animals in applied ethology studies  

Microsoft Academic Search

Applied ethology has a continuing interest in the promotion of animal welfare and the ethical treatment of animals used in research. However, in contrast to some other fields involving animal research, there are currently no guidelines written specifically for those engaged in applied ethology studies. We aim here, to provide members of the profession with a basis for structured self-evaluation

Chris M Sherwin; Stine B Christiansen; Ian J Duncan; Hans W Erhard; Don C Lay; Joy A Mench; Cheryl E O’Connor; J. Carol Petherick

2003-01-01

196

The role of animal behaviour in the study of endocrine-disrupting chemicals  

E-print Network

The role of animal behaviour in the study of endocrine-disrupting chemicals ETHAN D. CLOTFELTER are known to interfere with the endocrine systems of animals. These chemicals, commonly referred to as endocrine-disrupting chemicals (hereafter EDCs), pose a particularly severe threat to animal health

Clotfelter, Ethan

197

Dominant lethal study in CD-1 mice following inhalation exposure to 1,3-butadiene: Final technical report  

SciTech Connect

The effects of whole-body inhalation exposures to 1,3-butadiene on the reproductive system was evaluated. The results of dominant lethality in CD-1 male mice that were exposed to 1,3-butadiene are described. Subsequent to exposure, males were mated with two unexposed females. Mating was continued for 8 weeks with replacement of two females each week. Gravid uteri were removed, and the total number, position and status of implantations were determined. The mice were weighed prior to exposure and at 0, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after exposure and at sacrifice. The animals were observed for mortality, morbidity and signs of toxicity throughout the study. 19 refs., 5 figs., 9 tabs.

Hackett, P.L.; Mast, T.J.; Brown, M.G.; Clark, M.L.; Evanoff, J.J.; Rowe, S.E.; McClanahan, B.J.; Buschbom, R.L.; Decker, J.R.; Rommereim, R.L.; Westerberg, R.B.

1988-04-01

198

[Toxicological effects of nitrate: biological study in human and animal].  

PubMed

In order to evaluate the effects of the nitrates toxicity, a study has been carried out on 45 workers of storage and distribution agricultural manures, exposed to nitrate derivatives. Another experimental study has carried out in laboratory on male Albinos wistar rats. These latter were treated with ammonium nitrate (NH(4)NO(3)) introduced by gavage with three increasing concentrations 200, 400 and 600 mg/kg of body weight during three weeks. The biochemical and hematological results on workers showed that no poisoning was announced within this complex, in spite of the observation of kidneys inflammations among about 50% of the population. The chemical treatment of the rats causes a variation in the biochemical and biological parameters: an increase of the hepato-somatic ratio especially in the rats treated by important doses. Moreover, the serum concentration in glucose, cholesterol, creatinin, lactate dehydrogenase and in transaminases (GOT, GPT) was increased significantly compared to the witness in all the treated rats. At the end, the results obtained highlight the detoxifier potential expressed by the reduction in the glutathione level in the deferent organs such as the liver, the kidneys, the spleen, the intestines and the testicles. According to the obtained results, it can be concluded that: (1) living organism can adapt to the lows doses of nitrate for a long time. This is observed in the workers exposed to deferent derivatives of nitrates; (2) high nitrate amounts involve important biological variations even if the exposure time is short. This is proven in the laboratory animals. PMID:17627919

Boukerche, S; Aouacheri, W; Saka, S

2007-01-01

199

Attenuation correction for freely moving small animal brain PET studies based on a virtual scanner geometry  

NASA Astrophysics Data System (ADS)

Attenuation correction in positron emission tomography brain imaging of freely moving animals is a very challenging problem since the torso of the animal is often within the field of view and introduces a non negligible attenuating factor that can degrade the quantitative accuracy of the reconstructed images. In the context of unrestrained small animal imaging, estimation of the attenuation correction factors without the need for a transmission scan is highly desirable. An attractive approach that avoids the need for a transmission scan involves the generation of the hull of the animal’s head based on the reconstructed motion corrected emission images. However, this approach ignores the attenuation introduced by the animal’s torso. In this work, we propose a virtual scanner geometry which moves in synchrony with the animal’s head and discriminates between those events that traversed only the animal’s head (and therefore can be accurately compensated for attenuation) and those that might have also traversed the animal’s torso. For each recorded pose of the animal’s head a new virtual scanner geometry is defined and therefore a new system matrix must be calculated leading to a time-varying system matrix. This new approach was evaluated on phantom data acquired on the microPET Focus 220 scanner using a custom-made phantom and step-wise motion. Results showed that when the animal’s torso is within the FOV and not appropriately accounted for during attenuation correction it can lead to bias of up to 10% . Attenuation correction was more accurate when the virtual scanner was employed leading to improved quantitative estimates (bias < 2%), without the need to account for the attenuation introduced by the extraneous compartment. Although the proposed method requires increased computational resources, it can provide a reliable approach towards quantitatively accurate attenuation correction for freely moving animal studies.

Angelis, G. I.; Kyme, A. Z.; Ryder, W. J.; Fulton, R. R.; Meikle, S. R.

2014-10-01

200

The effect of nanoparticle properties, detection method, delivery route and animal model on poly(lactic-co-glycolic) acid nanoparticles biodistribution in mice and rats.  

PubMed

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

2014-05-01

201

Delay in the Recovery of Normal Sleep-Wake Cycle after Disruption of the Light-Dark Cycle in Mice: A Bipolar Disorder-Prone Animal Model?  

PubMed Central

Objective Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice. Methods Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.). Results The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test). Conclusion Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder. PMID:25395982

Jung, Sun Hwa; Moon, Eunsoo; Chung, Young In; Lee, Byung Dae; Lee, Young Min; Kim, Ji Hoon; Kim, Soo Yeon; Jeong, Hee Jeong

2014-01-01

202

Statistical Issues in the Design and Analysis of Gene Expression Microarray Studies of Animal Models  

Microsoft Academic Search

Appropriate statistical design and analysis of gene expression microarray studies is critical in order to draw valid and useful conclusions from expression profiling studies of animal models. In this paper, several aspects of study design are discussed, including the number of animals that need to be studied to ensure sufficiently powered studies, usefulness of replication and pooling, and allocation of

Lisa M. McShane; Joanna H. Shih; Aleksandra M. Michalowska

2003-01-01

203

Radioautographic studies on radiosulfate incorporation in the digestive organs of mice.  

PubMed

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

1999-07-01

204

ANIMAL MODELS FOR STUDYING MISCARRIAGE: ILLUSTRATION WITH STUDY OF DRINKING WATER DISINFECTION BY-PRODUCTS  

EPA Science Inventory

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...

205

Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system.  

PubMed

The nociceptin receptor (NOP) and its ligand nociceptin/orphanin FQ (N/OFQ) have been shown to exert a modulatory effect on immune cells during sepsis. We evaluated the suitability of an experimental lipopolysaccharide (LPS)-induced sepsis model for studying changes in the nociceptin system. C57BL/6 mice BALB/c mice and Wistar rats were inoculated with different doses of LPS with or without a nociceptin receptor antagonist (UFP-101 or SB-612111). In C57BL/6 mice LPS 0.85 mg/kg injection produced no septic response, whereas 1.2mg/kg produced a profound response within 5h. In BALB/c mice, LPS 4 mg/kg produced no response, whereas 7 mg/kg resulted in a profound response within 24h. In Wistar rats LPS 15 mg/kg caused no septic response in 6/10 animals, whereas 25mg/kg resulted in marked lethargy before 24h. Splenic interleukin-1? mRNA in BALB/c mice, and serum TNF-? concentrations in Wistar rats increased after LPS injection in a dose-dependent manner, but were undetectable in control animals, indicating that LPS had stimulated an inflammatory reaction. IL-1? and TNF-? concentrations in LPS-treated animals were unaffected by administration of a NOP antagonist. Similarly NOP antagonists had no effect on survival or expression of mRNA for NOP or ppN/OFQ (the N/OFQ precursor) in a variety of tissues. In these animal models, the dose-response curve for LPS was too steep to allow use in survival studies and no changes in the N/OFQ system occurred within 24h. We conclude that LPS-inoculation in rodents is an unsuitable model for studying possible changes in the NOP-N/OFQ system in sepsis. PMID:25161013

Thomas, Roisin C; Bath, Michael F; Stover, Cordula M; Lambert, David G; Thompson, Jonathan P

2014-11-01

206

Computer Animation  

NSDL National Science Digital Library

CSC 320. (ART 320) (FST 320) Computer Animation (3) Prerequisite: CSC 220 (ART 220) (FST 220) or permission of instructor. Basic principles of animation using 3-D computer-generated animation and basic processes for animating synthetic objects through structured exercises. Principles of designing and producing 3-D computer-generated animation through the creation of advanced motion studies. Projects focus on developing higher-level skills in model building, animation and color, and lighting.

Patterson, Eric

2003-04-21

207

Markerless 3D motion capture for animal locomotion studies.  

PubMed

Obtaining quantitative data describing the movements of animals is an essential step in understanding their locomotor biology. Outside the laboratory, measuring animal locomotion often relies on video-based approaches and analysis is hampered because of difficulties in calibration and often the limited availability of possible camera positions. It is also usually restricted to two dimensions, which is often an undesirable over-simplification given the essentially three-dimensional nature of many locomotor performances. In this paper we demonstrate a fully three-dimensional approach based on 3D photogrammetric reconstruction using multiple, synchronised video cameras. This approach allows full calibration based on the separation of the individual cameras and will work fully automatically with completely unmarked and undisturbed animals. As such it has the potential to revolutionise work carried out on free-ranging animals in sanctuaries and zoological gardens where ad hoc approaches are essential and access within enclosures often severely restricted. The paper demonstrates the effectiveness of video-based 3D photogrammetry with examples from primates and birds, as well as discussing the current limitations of this technique and illustrating the accuracies that can be obtained. All the software required is open source so this can be a very cost effective approach and provides a methodology of obtaining data in situations where other approaches would be completely ineffective. PMID:24972869

Sellers, William Irvin; Hirasaki, Eishi

2014-01-01

208

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.

1983-01-01

209

Markerless 3D motion capture for animal locomotion studies  

PubMed Central

ABSTRACT Obtaining quantitative data describing the movements of animals is an essential step in understanding their locomotor biology. Outside the laboratory, measuring animal locomotion often relies on video-based approaches and analysis is hampered because of difficulties in calibration and often the limited availability of possible camera positions. It is also usually restricted to two dimensions, which is often an undesirable over-simplification given the essentially three-dimensional nature of many locomotor performances. In this paper we demonstrate a fully three-dimensional approach based on 3D photogrammetric reconstruction using multiple, synchronised video cameras. This approach allows full calibration based on the separation of the individual cameras and will work fully automatically with completely unmarked and undisturbed animals. As such it has the potential to revolutionise work carried out on free-ranging animals in sanctuaries and zoological gardens where ad hoc approaches are essential and access within enclosures often severely restricted. The paper demonstrates the effectiveness of video-based 3D photogrammetry with examples from primates and birds, as well as discussing the current limitations of this technique and illustrating the accuracies that can be obtained. All the software required is open source so this can be a very cost effective approach and provides a methodology of obtaining data in situations where other approaches would be completely ineffective. PMID:24972869

Sellers, William Irvin; Hirasaki, Eishi

2014-01-01

210

Monte Carlo simulations studies in small animal PET using GATE  

Microsoft Academic Search

This work is focused on the use of a simulation system dedicated for small animal PET imaging, in order to produce realistic simulated mouse exams. Sets of gold standard images where physical effects not taken into account are presented. A preliminary approach of the physiological process of the respiratory motion and the implementation of a lung tumor is shown in

S. Branco; S. Jan; P. Almeida

2007-01-01

211

Animal models to study neonatal nutrition in humans  

Technology Transfer Automated Retrieval System (TEKTRAN)

The impact of neonatal nutrition on the health status of the newborn and incidence of disease in later life is a topic of intense interest. Animal models are an invaluable tool to identify mechanisms that mediate the effect of nutrition on neonatal development and metabolic function. This review hig...

212

Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice  

PubMed Central

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. PMID:21984939

Boll, Hanne; Nittka, Stefanie; Doyon, Fabian; Neumaier, Michael; Marx, Alexander; Kramer, Martin; Groden, Christoph; Brockmann, Marc A.

2011-01-01

213

3D visualization and quantification of bone and teeth mineralization for the study of osteo/dentinogenesis in mice models  

NASA Astrophysics Data System (ADS)

Research on bone and teeth mineralization in animal models is critical for understanding human pathologies. Genetically modified mice represent highly valuable models for the study of osteo/dentinogenesis defects and osteoporosis. Current investigations on mice dental and skeletal phenotype use destructive and time consuming methods such as histology and scanning microscopy. Micro-CT imaging is quicker and provides high resolution qualitative phenotypic description. However reliable quantification of mineralization processes in mouse bone and teeth are still lacking. We have established novel CT imaging-based software for accurate qualitative and quantitative analysis of mouse mandibular bone and molars. Data were obtained from mandibles of mice lacking the Fibromodulin gene which is involved in mineralization processes. Mandibles were imaged with a micro-CT originally devoted to industrial applications (Viscom, X8060 NDT). 3D advanced visualization was performed using the VoxBox software (UsefulProgress) with ray casting algorithms. Comparison between control and defective mice mandibles was made by applying the same transfer function for each 3D data, thus allowing to detect shape, colour and density discrepencies. The 2D images of transverse slices of mandible and teeth were similar and even more accurate than those obtained with scanning electron microscopy. Image processing of the molars allowed the 3D reconstruction of the pulp chamber, providing a unique tool for the quantitative evaluation of dentinogenesis. This new method is highly powerful for the study of oro-facial mineralizations defects in mice models, complementary and even competitive to current histological and scanning microscopy appoaches.

Marchadier, A.; Vidal, C.; Ordureau, S.; Lédée, R.; Léger, C.; Young, M.; Goldberg, M.

2011-03-01

214

Animal models of pancreatitis: Can it be translated to human pain study?  

PubMed Central

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. PMID:24259952

Zhao, Jing-Bo; Liao, Dong-Hua; Nissen, Thomas Dahl

2013-01-01

215

Pain and Distress Categories for Animal Studies Compared CURRENT U.T. CATEGORIES  

E-print Network

Pain and Distress Categories for Animal Studies Compared CURRENT U.T. CATEGORIES 1. ACUTE STUDIES under anesthesia or following euthanasia. Routine animal holding or breeding. 2. MINOR PAIN OR DISTRESS Studies without pain or distress other than associated with routine injections or blood collection. Can

Cui, Yan

216

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

2000-03-01

217

Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels  

PubMed Central

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. PMID:24858807

Sadda, Veeranjaneyulu; Nielsen, Gorm; Hedegaard, Elise Røge; Mogensen, Susie; Köhler, Ralf; Simonsen, Ulf

2014-01-01

218

Study on the Mechanical Instability of MICE Coupling Magnets  

SciTech Connect

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

2011-05-04

219

Collective behavior in animal groups: theoretical models and empirical studies  

PubMed Central

Collective phenomena in animal groups have attracted much attention in the last years, becoming one of the hottest topics in ethology. There are various reasons for this. On the one hand, animal grouping provides a paradigmatic example of self-organization, where collective behavior emerges in absence of centralized control. The mechanism of group formation, where local rules for the individuals lead to a coherent global state, is very general and transcends the detailed nature of its components. In this respect, collective animal behavior is a subject of great interdisciplinary interest. On the other hand, there are several important issues related to the biological function of grouping and its evolutionary success. Research in this field boasts a number of theoretical models, but much less empirical results to compare with. For this reason, even if the general mechanisms through which self-organization is achieved are qualitatively well understood, a quantitative test of the models assumptions is still lacking. New analysis on large groups, which require sophisticated technological procedures, can provide the necessary empirical data. PMID:19404431

Giardina, Irene

2008-01-01

220

How postnatal insults may program development: studies in animal models.  

PubMed

During the postnatal period, the nervous system is modified and shaped by experience, in order to adjust it to the particular environment in which the animal will live. This plasticity, one of the most remarkable characteristics of the nervous system, promotes adaptive changes, but it also makes brain more vulnerable to insults. This chapter will focus on the effects of interventions during the postnatal development in animal models of neonatal handling (usually up to 15 min of handling) and maternal separation (usually at least for 3 h). Sex-specific changes and effects of prepubertal stress such as social isolation later on in life were also considered. These interventions during development induce long-lasting traces in the pups' nervous system, which will be reflected in changes in neuroendocrine functions, including the hypothalamus-pituitary-adrenal and hypothalamus-pituitary-gonadal axes; anxiety and cognitive performance; and feeding, sexual, and social behavior. These enduring changes may be adaptive or maladaptive, depending on the environment in which the animal will live. The challenge researchers facing now is to determine how to reverse the deleterious effects that may result from early-life stress exposure. PMID:25287539

Dalmaz, Carla; Noschang, Cristie; Krolow, Rachel; Raineki, Charlis; Lucion, Aldo B

2015-01-01

221

Animal Diversity  

NSDL National Science Digital Library

This lesson from Science NetLinks exposes children to a wide range of animals and guides them through observation of animal similarities, differences, and environmental adaptations. This lesson can be used as part of a study of plants and animals. Before doing the lesson, students should know the meanings of the terms: plant, animal, and living.

Science Netlinks;

2004-02-05

222

Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders.  

PubMed

The purinergic P2X(7) receptor is a ligand-gated ion channel found on peripheral macrophages and microglia in the nervous system. Activation of P2X(7) receptors results in the rapid release of interleukin-1 beta (IL-1 beta). Cytokines like IL-1 beta are suggested to be involved in the pathophysiology of depression. The aim of this study was to behaviorally profile P2X(7) receptor knockout (KO) mice in behavioral models of depression- and anxiety-like behaviors. P2X(7) receptor KO and wild type (WT) mice were tested in multiple models including; forced swim test, tail suspension test, elevated plus maze, novelty suppressed feeding, spontaneous locomotor activity, and food intake. P2X(7) receptor KO mice exhibited an antidepressant-like profile in tail suspension test and forced swim test; an effect that was not associated with changes in spontaneous locomotor activity. In addition, P2X(7) receptor KO mice showed higher responsivity to a subefficacious dose of the antidepressant drug imipramine (15 mg/kg) in forced swim test. No significant differences between genotypes were observed in models of anxiety. These data support the relevance of pro-inflammatory cytokines in depressive-like states, and suggest that P2X(7) receptor antagonists could be of potential interest for the treatment of affective disorders. PMID:18996151

Basso, Ana M; Bratcher, Natalie A; Harris, Richard R; Jarvis, Michael F; Decker, Michael W; Rueter, Lynne E

2009-03-01

223

Modality comparison for small animal radiotherapy: A simulation study  

SciTech Connect

Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200?kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4?Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. Conclusions: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.

Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.; Graves, Edward E. [Department of Radiation Oncology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305 (United States)] [Department of Radiation Oncology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305 (United States)

2014-01-15

224

Modality comparison for small animal radiotherapy: A simulation study  

PubMed Central

Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200?kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4?Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. Conclusions: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems. PMID:24387502

Bazalova, Magdalena; Nelson, Geoff; Noll, John M.; Graves, Edward E.

2014-01-01

225

Effect of amphetamine on extracellular concentrations of amino acids in striatum in neurotensin subtype 1 and 2 receptor null mice: a possible interaction between neurotensin receptors and amino acid systems for study of schizophrenia  

PubMed Central

Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors: NTS1 and NTS2. The present study was done to determine the roles of NTS1 and NTS2 on amino acid release in striatum with the use of NTS1 or NTS2 knock-out (-/-) mice given d-amphetamine. Both NTS1-/- and NTS2-/- mice had lower extracellular concentrations of D-serine in striatum than did wild type (WT) mice. NTS2-/- but not NTS1-/- mice also had significantly lower basal concentrations of glutamate in striatum as compared to that for WT mice. Systemic administration of d-amphetamine (4 mg/kg, ip) increased glutamate release by 500% in WT mice, as compared to 300% in NTS2-/- mice, and 250% in NTS1-/- mice. Additionally, d-amphetamine injection caused a 4-fold increase in GABA release in both WT and NTS2-/- mice, but only a 2-fold increase in NTS1-/- mice. Therefore, NTS1 and NTS2 modulate basal release of D-serine and glutamate, and also d-amphetamine-induced GABA and glutamate release in striatum. These results provide further support for the involvement of NT receptors in the pathogenesis of schizophrenia and provide a better understanding of the imbalance of amino acid systems through investigation of a DA-based animal model. PMID:20193696

Li, Zhimin; Liang, Yanqi; Boules, Mona; Gordillo, Andres; Richelson, Elliott

2010-01-01

226

Animal models for the study of liver fibrosis: new insights from knockout mouse models  

PubMed Central

Fibrosis arises as part of a would-healing response that maintains organ structure and integrity following tissue damage but also contributes to a variety of human pathologies such as liver fibrosis. Liver fibrosis is an abnormal response of the liver to persistent injury with the excessive accumulation of collagenous extracellular matrices. Currently there is no effective treatment, and many patients end up with a progressive form of the disease, eventually requiring a liver transplant. The clarification of mechanisms underlying pathogenesis of liver fibrosis and the development of effective therapy are of clinical importance. Experimental animal models, in particular targeted gene knockouts (loss of function) in mice, have become a powerful resource to address the molecular mechanisms or significance of the targeted gene in hepatic functions and diseases. This review will focus on the recent advances in knowledge obtained from genetically engineered mice that provide novel insights into the pathophysiology of liver fibrosis. PMID:21350186

Hayashi, Hiromitsu

2011-01-01

227

An XRF study of trace elements accumulation in kidneys of tumor-bearing mice after treatment with cis DDP with and without selenite and selenocistamine  

Microsoft Academic Search

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

1994-01-01

228

Second hand smoke and COPD: lessons from animal studies  

PubMed Central

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. PMID:23450717

Goldklang, Monica P.; Marks, Sarah M.; D'Armiento, Jeanine M.

2013-01-01

229

Insights from the Study of Animals Lacking Functional Estrogen Receptor  

NASA Astrophysics Data System (ADS)

Estrogen hormones produce physiological actions within a variety of target sites in the body and during development by activating a specific receptor protein. Hormone responsiveness for the estrogen receptor protein was investigated at different stages of development with the use of gene knockout techniques because no natural genetic mutants have been described. A mutant mouse line without a functional estrogen receptor was created and is being used to assess estrogen responsiveness. Both sexes of these mutant animals are infertile and show a variety of phenotypic changes, some of which are associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues.

Korach, Kenneth S.

1994-12-01

230

The Value of Animations in Biology Teaching: A Study of Long-Term Memory Retention  

Microsoft Academic Search

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

2007-01-01

231

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

232

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.  

PubMed

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

2010-12-01

233

Orally active alpha-ketohydroxypyridine iron chelators: studies in mice  

SciTech Connect

Several N-substituted 3-hydroxypyrid-2-one and N-substituted 2-methyl-3-hydroxypyrid-4-one chelators were screened for /sup 59/Fe removal using iron-overloaded mice labeled with /sup 59/Fe. The most effectice chelators were found to be the N-methyl, N-ethyl, and N-propyl derivatives of 2-methyl-3-hydroxypyrid-4-one. When the above three chelators were administered intragastrically or intraperitoneally (200 mg/kg) to mice, they caused equivalent /sup 59/Fe excretions to intraperitoneal desferrioxamine (200 mg/kg). These results increase the prospects for the use of the alpha-ketohydroxypyridine chelators in the treatment of iron overload.

Kontoghiorghes, G.J.

1986-12-01

234

[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].  

PubMed

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

2006-01-01

235

Interleukin-6 reduces cartilage destruction during experimental arthritis. A study in interleukin-6-deficient mice.  

PubMed Central

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 PMID:9212744

van de Loo, F. A.; Kuiper, S.; van Enckevort, F. H.; Arntz, O. J.; van den Berg, W. B.

1997-01-01

236

Olfactory sensitivity for six amino acids: a comparative study in CD-1 mice and spider monkeys.  

PubMed

Using a conditioning paradigm, the olfactory sensitivity of five CD-1 mice for the L- and D-forms of cysteine, methionine, and proline was investigated. With all six stimuli, the animals discriminated concentrations ? 0.1 ppm (parts per million) from the odorless solvent, and with three of the six stimuli the best-scoring animals were even able to detect concentrations <0.1 ppb (parts per billion). Three spider monkeys tested in parallel were found to detect the same six stimuli at concentrations <1 ppm, and with four of the six stimuli the best-scoring animals detected concentrations ? 1 ppb. Both CD-1 mice and spider monkeys displayed a higher olfactory sensitivity with the L- and D-forms of cysteine and methionine than with the prolines, suggesting an important role of the sulfur-containing functional groups for detectability. Accordingly, the across-odorant patterns of detection thresholds obtained with mice and spider monkeys showed a significant positive correlation. A comparison of the detection thresholds between the two species tested here and those obtained in human subjects suggests that neither the number of functional olfactory receptor genes nor the absolute or the relative size of the olfactory bulbs reliably predicts a species' olfactory sensitivity for amino acids. PMID:21647661

Wallén, Helena; Engström, Ida; Hernandez Salazar, Laura Teresa; Laska, Matthias

2012-04-01

237

Applications of stable isotopes to study plant-animal relationships in terrestrial ecosystems  

Microsoft Academic Search

As natural tracers, stable isotopes have been extensively used in plant physiological, ecological and environmental research.\\u000a Recently, animal physiological ecologists have also applied stable isotope techniques to study plantanimal relationships.\\u000a The isotopic compositions of animal body generally reflect and integrate their diets over a time period ranging from hours\\u000a to years to the lifetime of an individual. When animal living

Jianzhu Wang; Guanghui Lin; Jianhui Huang; Xingguo Han

2004-01-01

238

Pharmacological studies on the venomous spotted butterfish (Scatophagus argus Linn) sting extract on experimental animals.  

PubMed

A sting of the fish S. argus, a venomous edible spotted butterfish, produces tremendous local pain, severe swelling, rise of body temperature, throbbing sensation etc. To establish the pharmacological activities of S. argus sting extract, the present investigation, was carried out on experimental animals. The LD50 of extract was found to be 9.3 mg/kg (iv) in male albino mice. The extract showed loss of sensation, urination and salivation in mice. It potentiated pentobarbitone induced sleeping time in male albino mice and produced hypothermia. Extract produced a fall of cat and guinea pig blood pressure, which was completely abolished by mepyramine. It produced a transient reduction of respiratory rate in rat, but decreased respiratory amplitude in cat, which was abolished after vagotomy. On isolated toad heart, the extract increased both the amplitude and rate of contraction. On isolated guinea pig heart, the sting extract decreased both the rate and amplitude of contraction leading to cardiac arrest, but it had no effect on isolated guinea pig auricle. The extract produced a reversible blockade of electrically induced twitch response of isolated chick biventer cervices preparation, but it had no effect on the isolated rat phrenic nerve diaphragm preparation. It produced a slow contractile response on isolated guinea pig ileum, rat uterus and rat fundal strip preparations but produced slow relaxation on isolated rat duodenum preparation. The contractile response on isolated guinea pig ileum and rat fundal strip was antagonised by SC19220. It did not produce any significant cutaneous haemorrhage in mice and did not produce any haemolysis on saline washed erythrocytes. The sting extract significantly increased capillary permeability of guinea pig dorsal flank and produced oedema in mice hind paw. PMID:15233469

Muhuri, D; Karmakar, S; Dasgupta, S C; Nagchaudhuri, A K; Gomes, A

2004-05-01

239

The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies  

PubMed Central

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified. PMID:25541545

de Vries, Rob B. M.; Wever, Kimberley E.; Avey, Marc T.; Stephens, Martin L.; Sena, Emily S.; Leenaars, Marlies

2014-01-01

240

A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice.  

PubMed

The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis. PMID:17904263

Choi, Eun Mi; Kim, Young Ho

2008-01-01

241

Effect of high sugar levels on miRNA expression. Studies with galactosemic mice lenses  

PubMed Central

Purpose Development of cataract is associated with apoptotic death of the lens epithelial cells. The purpose of this investigation was to examine whether this could be explained by enhancement in the expression of certain pro-apoptotic microRNAs (miRs), known to induce apoptosis by hybridizing with target mRNAs, with the consequence of gene silencing. In addition, it was intended to investigate if such expression could be antagonized by reactive oxygen species (ROS) scavengers. Methods CD-1 mice weighing about 20 g were divided into three groups and fed diets, respectively, as follows: Control diet, 25% galactose diet, and 25% galactose diet containing 1% sodium pyruvate. After eight days of such a regimen, the mice were euthanized, their lenses promptly isolated and frozen in liquid nitrogen, and RNAs isolated by extraction with standard methods and converted to cDNAs. The miR-specific cDNAs were then quantified by polymerase chain reaction (PCR) using a 96-well microRNA array cassette using an ABI 7900 HT PCR machine. The results were then analyzed using Bioscience software. Results The lens samples were positive for all of the 84 miRs expected, on the basis of the specific sequences used for amplification. However, as would be apparent from the microarray plot for the normal and galactosemic lenses, expression of at least 24 apoptotic miRs was upregulated. Six apoptotic miRs were downregulated. In the lenses of animals where the galactose diet was fortified with sodium pyruvate, the expression of 12 miRs was completely prevented. The upregulation observed in the other 14 miRs was also significantly downregulated. A comparison of the galactose and galactose plus pyruvate group clearly indicated that pyruvate inhibits the transcription of apoptotic miRS. Conclusions The prevention of galactose-induced enhancement in the expression of apoptotic miRs by pyruvate, a compound well known to scavenge reactive oxygen species as well as to inhibit their formation, strongly suggests that the upregulation of miRs in galactosemic animals is due to generation of reactive oxygen species. This is in conformity with our previous studies showing that pyruvate and other ROS scavengers inhibit apoptosis as well as cataract formation. PMID:22736950

Kovtun, Svitlana; Hegde, Kavita; Yin, Jing; Ramnath, Jamuna

2012-01-01

242

The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier.  

PubMed

An integrated assay system involving dual/triple-probe microdialysis techniques in rats was developed earlier for testing interactions with P-glycoprotein (P-gp) at the blood-brain barrier using quinidine/PSC-833 as a P-gp substrate/inhibitor combination. The aim of the present study was to expand our assay system to mice using microdialysis with simultaneous sampling of blood and brain and to compare the result with a primary mouse brain endothelial cell monolayer (pMBMEC) assay. Brain penetration of quinidine was dose dependent in both anesthetized and awake mice after intraperitoneal drug administration. PSC-833 pretreatment caused a 2.5- to 3.4-fold increase in quinidine levels of brain dialysate samples in anesthetized or awake animals, after single or repeated administration of PSC-833. In pMBMEC, a 2.0- to 2.5-fold efflux ratio was observed in the transcellular transport of quinidine. The P-gp-mediated vectorial transport of quinidine was eliminated by PSC-833. These results indicate that quinidine with PSC-833 is a good probe substrate-reference inhibitor combination for testing drug-drug interactions with P-gp in the in vivo and in vitro mouse systems. With increasing number of humanized transgenic mice, a test system with mouse microdialysis experimentation becomes more important to predict drug-drug interactions in humans. PMID:23204072

Sziráki, István; Erd?, Franciska; Trampus, Péter; Sike, Mirabella; Molnár, Petra Magdolna; Rajnai, Zsuzsanna; Molnár, Judit; Wilhelm, Imola; Fazakas, Csilla; Kis, Emese; Krizbai, István; Krajcsi, Péter

2013-04-01

243

Laboratory studies of imitation/field studies of tradition: Towards a synthesis in animal social learning.  

PubMed

Here I discuss: (1) historical precedents that have resulted in comparative psychologists accepting the two-action method as the "gold standard" in laboratory investigations of imitation learning, (2) evidence suggesting that the two-action procedure may not be adequate to answer questions concerning the role of imitation in the development of traditional behaviors of animals living in natural habitat, and (3) an alternative approach to the laboratory study of imitation that might increase the relevance of laboratory studies of imitation to the work of behavioral ecologists/primatologists interested in animal traditions and their relationship to human cumulative culture. This article is part of a Special Issue entitled: Tribute to Tom Zentall. PMID:25058622

Galef, Bennett G

2015-03-01

244

Studies on analgesic activity of Cleome viscosa in mice.  

PubMed

The analgesic activity of methanol extract of Cleome viscosa, given orally at the doses of 100, 200, 400 mg/kg was evaluated for its analgesic activity in mice using the acetic acid-induced writhing and the tail flick, tail clip, tail immersion methods. The extract showed promising activity in all the tests. PMID:12727491

Parimaladevi, B; Boominathan, R; Mandal, S C

2003-04-01

245

CYTOGENETIC STUDIES OF MICE EXPOSED TO STYRENE BY INHALATION  

EPA Science Inventory

The published data for the in vivo genotoxicity of styrene (STY) are equivocal. o evaluate the clastogenicity and sister chromatid exchange (SCE)-inducing potential of STY in vivo under carefully controlled conditions, 36C3F1 female mice were exposed by inhalation for 6 hours/day...

246

INHALATION TERATOLOGY STUDIES OF CAPTAN AND FOLPET IN MICE  

EPA Science Inventory

Timed pregnant CD-1 mice were exposed to captan or folpet by the intragastric, subcutaneous or inhalation route. A dose of 100 mg/kg/day of captan or folpet was administered subcutaneously or intragastrically from day 6-15 of gestation. The dose levels for the inhalation route we...

247

PERINATAL STUDY OF TOLUENE IN CD-1 MICE  

EPA Science Inventory

Toluene administered by inhalation at 400 ppm to CD-1 mice from Days 6 to 16 of gestation was teratogenic but not fetotoxic resulting in a significant shift in the fetal rib profile. At the lower concentration of 200 ppm, there was an increase in dilated renal pelves which might ...

248

Further studies on trypanosomers in game animals in Wyoming.  

PubMed

Blood samples were collected from captive and free-ranging elk (Cervus canadensis), mule deer (Odocoileus hemionus), white-tailed deer, (Odocoileus virginianus), black-tailed deer (Odocoileus hemionus columbianus), pronghorn (Antilocapra americana), moose (Alces alces), and bighorn sheep (Ovis canadensis) for cultural evidence of Trypanosoma sp. infection. Eleven of 188 (12%) hunter-killed elk, 22 of 37 (59%) free-ranging elk, and 79 of 119 (66%) captive elk were culture positive in 1973-74. Parasitemia in adult captive elk showed seasonal variation. Other captive or live-trapped animals found positive included 16 mule deer, two white-tailed deer, and one black-tailed deer. No pronghorn, moose, or bighorn sheep were positive. A 0.25 ml inoculum of elk blood was sufficient to give positive culture results. Small sample size may have contributed to negative results from elk trapped in March 1973. PMID:933315

Morton, J K; Kingston, N

1976-04-01

249

Use of (Gyro) Gy and spermine synthase transgenic mice to study functions of spermine.  

PubMed

The polyamines putrescine, spermidine, and spermine are essential for mammalian cell growth, -differentiation, and cell death and have important physiological roles in all tissues. Many of the properties of polyamines that can be demonstrated in vitro are common to all three molecules with differences only in potency. Loss of any of the enzymes needed to make either putrescine or spermidine (which also -prevent the production of spermine) is lethal, but male mice lacking spermine synthase (SpmS) due to a deletion of part of the X chromosome are viable on the B6C3H background. These mice are termed Gyro (Gy) due to their circling behavior. They have a variety of abnormalities including deafness, neurological problems, small size, and a tendency to early death. They can therefore be used to evaluate the physiological function(s) uniquely provided by spermine. They also provide a potential animal model for Snyder-Robinson syndrome (SRS), a rare human inherited disease due to a loss of SpmS activity. An essential control in experiments using Gy mice is to demonstrate that the abnormal phenotypes exhibited by these mice are abolished by providing replacement spermine and this can be accomplished by breeding with CAG-SMS mice that express SpmS from a ubiquitous promoter. Techniques for identifying, characterizing, and using these mouse strains and limitations of this approach are described in this chapter. PMID:21318872

Wang, Xiaojing; Pegg, Anthony E

2011-01-01

250

A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)  

SciTech Connect

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.

HABER, S.B.

1987-06-26

251

A step-by-step guide to systematically identify all relevant animal studies  

PubMed Central

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

2012-01-01

252

A comparative approach to the study of Keeper-Animal Relationships in the zoo.  

PubMed

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

2009-11-01

253

Alkali burn versus suture-induced corneal neovascularization in C57BL/6 mice: an overview of two common animal models of corneal neovascularization.  

PubMed

The purpose of the present study was to quantify and compare corneal hem- and lymphangiogenesis between alkali burn and suture-induced corneal neovascularization (CNV) in two commonly used mouse strains. A retrospective analysis was performed on C57BL/6 and FVB neovascularized corneas. CNV was induced by surface caustication with NaOH or intrastromal placement of three 10.0 nylon sutures. Hemangiogenesis and lymphangiogenesis extent was calculated on whole mounted corneas by CD31 and LYVE1 immunofluorescence analysis. Blood vessel growth was similar between alkali burn and suture-induced CNV in C57BL/6 mice, and between C57BL/6 and FVB sutured strains. On the contrary, corneal lymphangiogenesis was more pronounced in the C57BL/6 sutured mice versus the alkali burn group, and in the FVB strain versus both C57BL/6 models. These results indicate that significant differences occur in lymphangiogenesis, but not hemangiogenesis, in the alkali burn and suture-induced models in C57BL/6 mice. Furthermore, lymphangiogenesis is more pronounced in the albino (FVB) strain after suture placement. We suggest that the suture model has a number of advantages and may be preferentially used to study corneal lymphangiogenesis. PMID:24560796

Giacomini, Chiara; Ferrari, Giulio; Bignami, Fabio; Rama, Paolo

2014-04-01

254

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

2012-01-01

255

The Value of Animations in Biology Teaching: A Study of Long-Term Memory Retention  

ERIC Educational Resources Information Center

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…

O'Day, Danton H.

2007-01-01

256

The acute effects of corticosteroids on cognition: integration of animal and human model studies  

Microsoft Academic Search

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

1997-01-01

257

Reduced wheel running and blunted effects of voluntary exercise in LPA1-null mice: The importance of assessing the amount of running in transgenic mice studies  

PubMed Central

This work was aimed to assess whether voluntary exercise rescued behavioral and hippocampal alterations in mice lacking the lysophosphatidic acid LPA1 receptor (LPA1-null mice), studying the potential relationship between the amount of exercise performed and its effects. Normal and LPA1-null mice underwent 23 days of free wheel running and were tested for open-field behavior and adult hippocampal neurogenesis (cell proliferation, immature neurons, cell survival). Running decreased anxiety-like behavior in both genotypes but increased exploration only in the normal mice. While running affected all neurogenesis-related measures in normal mice (especially in the suprapyramidal blade of the dentate gyrus), only a moderate increase in cell survival was found in the mutants. Importantly, the LPA1-nulls showed notably reduced running. Analysis suggested that defective running in the LPA1-null mice could contribute to explain the scarce benefit of the voluntary exercise treatment. On the other hand, a literature review revealed that voluntary exercise is frequently used to modulate behavior and the hippocampus in transgenic mice, but half of the studies did not assess the quantity of running, overlooking any potential running impairments. This study adds evidence to the relevance of the quantity of exercise performed, emphasizing the importance of its assessment in transgenic mice research. PMID:24055600

Castilla-Ortega, Estela; Rosell-Valle, Cristina; Blanco, Eduardo; Pedraza, Carmen; Chun, Jerold; de Fonseca, Fernando Rodríguez; Estivill-Torrús, Guillermo; Santín, Luis J.

2014-01-01

258

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.

1984-01-01

259

Renal Tubular Cells Cultured from Genetically Modified Animals  

Microsoft Academic Search

The culture of renal tubular cells from genetically modified animals opens the opportunity of biochemical, cell biology and physiological studies under strictly controlled conditions. Either primary cultures or cell lines can be used. Through two examples of primary cultures of proximal tubular cells obtained from knock-out mice, important information about the function of proteins were obtained. Mice lacking vimentin, an

Gérard Friedlander; Isabelle Runembert; François Vrtovsnik; Fabiola Terzi

1999-01-01

260

Welfare Issues of Genetically Modified Animals  

Microsoft Academic Search

Abstract Genetically engineered animals have opened,new frontiers in the study of physiology and disease processes. Mutant animals offer more,accurate disease models,and increased precision for pathogenesis and treatment studies. Their use offers hope for improved,therapy to patients with conditions that currently have poor or ineffective treatments. These advantages have fostered an increase in studies using mice in recent years, a development

Melvin B. Dennis

1989-01-01

261

Progression and regression of atherosclerosis in APOE3Leiden transgenic mice: an immunohistochemical study  

Microsoft Academic Search

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages

Marion J. J Gijbels; Maarten van der Cammen; Luc J. W van der Laan; Jef J Emeis; Louis M Havekes; Marten H Hofker; Georg Kraal

1999-01-01

262

Toxicology and carcinogenesis studies of microencapsulated trans-cinnamaldehyde in rats and mice  

Microsoft Academic Search

trans-Cinnamaldehyde is a widely used natural ingredient that is added to foods and cosmetics as a flavoring and fragrance agent. Male and female F344\\/N rats and B6C3F1 mice were exposed to microencapsulated trans-cinnamaldehyde in the feed for three months or two years. All studies included untreated and vehicle control groups. In the three-month studies, rats and mice were given diets

M. J. Hooth; R. C. Sills; L. T. Burka; J. K. Haseman; K. L. Witt; D. P. Orzech; A. F. Fuciarelli; S. W. Graves; J. D. Johnson; J. R. Bucher

2004-01-01

263

Utility of endogenous creatinine clearance as a measure of renal function in mice  

Microsoft Academic Search

Utility of endogenous creatinine clearance as a measure of renal function in mice.BackgroundThe use of endogenous plasma creatinine levels and creatinine clearance as a tool to evaluate renal function in mice has come under scrutiny as prior studies have reported that the Jaffé alkaline picrate method grossly overestimates true plasma creatinine in mice. As members of the NIDDK Animal Models

Stephen R. Dunn; Zhonghua Qi; Erwin P. Bottinger; Matthew D. Breyer; Kumar Sharma

2004-01-01

264

Morphometric study of the gubernaculum in male estrogen receptor mutant mice.  

PubMed

To determine role of estrogen receptors in testicular descent, a morphometric study of the testis and structures derived from the gubernaculum was made in sexually mature male mice having an estrogen receptor disrupted gene mutation (ERKO). Macroscopic dissections and sagittal serial sections were made of the pelvis of four wild-type mice, four mice heterozygous for the ERKO mutation, and four homozygous ERKO males. By external morphological examination the testes appeared to be descended in all three genotypes. All mice had development of a cremaster sac, which is derived from the gubernaculum, but this was twice as large in wild-type mice than in both the heterozygote or homozygote ERKO groups. The cause for the smaller cremaster sac appeared to be excessive development of the cremaster muscle in ERKO mice. The thickened muscle was associated with postmortem retraction of the testes into the inguinal canal or abdomen. Spermatogenesis and testicular volume were deficient in homozygous ERKO mice at this age. This study demonstrates that estrogen has a previously unknown role in masculine sexual development of the gubernaculum and the structures derived from it, such as the cremaster muscle. PMID:8723431

Donaldson, K M; Tong, S Y; Washburn, T; Lubahn, D B; Eddy, E M; Hutson, J M; Korach, K S

1996-01-01

265

Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice  

PubMed Central

Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate the physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by the Cre-recombinase-Locus of X-over P1(Cre-LoxP) system and studied SM digestion. Both wild-type (WT) and KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum, and liver were analyzed by TLC. In KO mice, nondigested 3H-SM in the intestinal content increased by 6-fold and the formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H-ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was decreased by 95%. After 3 h, a small increase in 3H-ceramide was identified in distal intestine in KO mice. In feces, 3H-SM was increased by 243% and ceramide decreased by 74% in the KO mice. The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore, alkaline phosphatase activity in the mucosa was reduced by 50% and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. This study provides definite proof for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function. PMID:21177474

Zhang, Yao; Cheng, Yajun; Hansen, Gert H.; Niels-Christiansen, Lise-Lotte; Koentgen, Frank; Ohlsson, Lena; Nilsson, Åke; Duan, Rui-Dong

2011-01-01

266

Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.  

PubMed

Coffin-Lowry syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes RSK2, a serine/threonine kinase acting in the MAPK/ERK pathway. The mouse invalidated for the Rps6ka3 (Rsk2-KO) gene displays learning and long-term spatial memory deficits. In the current study, we compared hippocampal gene expression profiles from Rsk2-KO and normal littermate mice to identify changes in molecular pathways. Differential expression was observed for 100 genes encoding proteins acting in various biological pathways, including cell growth and proliferation, cell death and higher brain function. The twofold up-regulated gene (Gria2) was of particular interest because it encodes the subunit GLUR2 of the AMPA glutamate receptor. AMPA receptors mediate most fast excitatory synaptic transmission in the central nervous system. We provide evidence that in the hippocampus of Rsk2-KO mice, expression of GLUR2 at the mRNA and at the protein levels is significantly increased, whereas basal AMPA receptor-mediated transmission in the hippocampus of Rsk2-KO mice is significantly decreased. This is the first time that such deregulations have been demonstrated in the mouse model of the Coffin-Lowry syndrome. Our findings suggest that a defect in AMPA neurotransmission and plasticity contribute to mental retardation in CLS patients. PMID:21116650

Mehmood, Tahir; Schneider, Anne; Sibille, Jérémie; Sibillec, Jérémie; Marques Pereira, Patricia; Pannetier, Solange; Ammar, Mohamed Raafet; Dembele, Doulaye; Thibault-Carpentier, Christelle; Rouach, Nathalie; Hanauer, André

2011-03-01

267

Tumorigenicity study of l-theanine administrated orally to mice  

Microsoft Academic Search

l-Theanine was orally administered at a concentration of 0–5% (maximum tolerated dose) of the diet to B6C3F1 mice for 13 weeks in a subacute test and 78 consecutive weeks, in a chronic toxicity test. There were no significant differences in intake of diet, weight gains or survival rates between treated and control groups. Unignorable differences in tumor incidence were observed

S. Fujii; K. Inai

2008-01-01

268

Benchmark dose and the three Rs. Part II. Consequences for study design and animal use.  

PubMed

OECD test guidelines for standard toxicity studies prescribe (minimal) numbers of animals, but these are not substantiated by a quantitative analysis of the relationship between number of animals and the required performance of the associated study design. This paper provides a general approach of how this relationship may be established and discusses the approach in more detail by focusing on the three typical repeated-dose studies (subacute, subchronic, and chronic). Quantitative results derived from simulation studies, including some new results, are summarized and their consequences for study guidelines are discussed. The currently prescribed study designs for repeated-dose studies do not appear to be sufficient when the NOAEL is used for evaluating the data--the probability of not detecting toxicologically significant effects is high. The ensuing need for increasing the number of animals may be avoided by replacing the NOAEL approach by the BMD approach as it increases the probability of detecting the same effects without increasing the number of animals. Hence, applying the BMD approach will result in a virtual reduction in the number of animals. Further, the BMD approach allows for a real reduction in the number of animals on various grounds. It allows for analyzing combined similar datasets, resulting in an increase in precision, which can be translated in animal reduction while keeping the same precision. In addition, applying the BMD approach may be expected to result in animal reduction in the long run, as it allows for distributing the same number of animals over more doses without loss of precision. The latter will reduce the need to repeat studies due to unfortunate dose location. PMID:25000331

Slob, Wout

2014-08-01

269

Radioimmunotherapy of athymic mice bearing human colon carcinomas with monoclonal antibody B72.3: histological and autoradiographic study of effects on tumors and normal organs.  

PubMed

Monoclonal antibody (MAb) B72.3 has been linked successfully to several radionuclides forming stable complexes and analyzed in vitro and in vivo without significant loss of its immunoreactivity. Previous studies have demonstrated that radioiodinated B72.3 can selectively bind to human colorectal carcinomas grown in athymic mice. The same successful localization has been obtained more recently in clinical trials in patients with metastatic colorectal carcinomas. The high degree of selective binding of this MAb has led us to investigate its potential as a radioimmunotherapeutic agent. Athymic mice bearing human colon carcinoma xenografts were injected with either 300 or 500 microCi of 131I-B72.3 IgG to assess the effect o the radiolabeled MAb on the tumor growth as well as potential toxic side effects in vital organs. In mice treated with the 131I-B72.3 IgG, a marked inhibition of the growth of the human colon carcinoma xenografts was noticed in comparison with control mice injected with PBS or control mice that received unlabeled B72.3 IgG. The tumors from these control mice weighed 2.7 to 3.7 times more than the tumors from the treated mice at 17 days post-inoculation of the radiolabeled MAb. Autoradiographic studies demonstrated a heterogeneous distribution of radioactivity throughout the tumor mass at 11 days post-administration of MAb. With time, the periphery of the tumor contained significantly less radioactivity than the medial areas composed of predominantly nonviable tissue; these findings suggest that the more biologically active peripheral tumor zones, with higher mitotic rates, could have partially escaped the radiation effect of the single dose administered. The tumor cells could have continued dividing when the levels of circulating radiolabeled monoclonal antibody had decreased. Toxicity was readily evident in the mice injected with the high-dose regimen (500 microCi), with confirmed bone marrow aplasia that proved lethal for 2 of 10 animals. The lower dose (300 microCi) resulted in a bone marrow suppression of approx. 50% of the cells, which proved to be non-lethal. The tumors in the treated mice showed extensive necrosis caused by the lethal dose of 131I-B72.3 that irreversibly damaged the cells. Radiation-induced terminal differentiation of cells was also found as manifested by the drastically decreased mitotic count (0-2 vs. 12-14 per 10 high power fields seen in control tumors) in treated animals. PMID:2820742

Esteban, J M; Schlom, J; Mornex, F; Colcher, D

1987-06-01

270

124I-Labeled Engineered Anti-CEA Minibodies and Diabodies Allow High-Contrast, Antigen-Specific Small-Animal PET Imaging of Xenografts in Athymic Mice  

PubMed Central

Prolonged clearance kinetics have hampered the development of intact antibodies as imaging agents, despite their ability to effectively deliver radionuclides to tumor targets in vivo. Genetically engineered antibody fragments display rapid, high-level tumor uptake coupled with rapid clearance from the circulation in the athymic mouse/LS174T xenograft model. The anticarcinoembryonic antigen (CEA) T84.66 minibody (single-chain Fv fragment [scFv]-CH3 dimer, 80 kDa) and T84.66 diabody (non-covalent dimer of scFv, 55 kDa) exhibit pharmacokinetics favorable for radioimmunoimaging. The present work evaluated the minibody or diabody labeled with 124I, for imaging tumor-bearing mice using a high-resolution small-animal PET system. Methods Labeling was conducted with 0.2–0.3 mg of protein and 65–98 MBq (1.7–2.6 mCi) of 124I using an iodination reagent. Radiolabeling efficiencies ranged from 33% to 88%, and immunoreactivity was 42% (diabody) or >90% (minibody). In vivo distribution was evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA-positive) and C6 rat glioma (CEA-negative) xenografts. Mice were injected via the tail vein with 1.9–3.1 MBq (53–85 ?Ci) of 124I-minibody or with 3.1 MBq (85 ?Ci) of 124I-diabody and imaged at 4 and 18 h by PET. Some mice were also imaged using 18F-FDG 2 d before imaging with 124I-minibody. Results PET images using 124I-labeled mini-body or diabody showed specific localization to the CEA-positive xenografts and relatively low activity elsewhere in the mice, particularly by 18 h. Target-to-background ratios for the LS174T tumors versus soft tissues using 124I-minibody were 3.05 at 4 h and 11.03 at 18 h. Similar values were obtained for the 124I-diabody (3.95 at 4 h and 10.93 at 18 h). These results were confirmed by direct counting of tissues after the final imaging. Marked reduction of normal tissue activity, especially in the abdominal region, resulted in high-contrast images at 18 h for the 124I-anti-CEA diabody. CEA-positive tumors as small as 11 mg (<3 mm in diameter) could be imaged, and 124I-anti-CEA minibodies, compared with 18F-FDG, demonstrated highly specific localization. Conclusion 124I labeling of engineered antibody fragments provides a promising new class of tumor-specific probes for PET imaging of tumors and metastases. PMID:14660722

Sundaresan, Gobalakrishnan; Yazaki, Paul J.; Shively, John E.; Finn, Ronald D.; Larson, Steven M.; Raubitschek, Andrew A.; Williams, Lawrence E.; Chatziioannou, Arion F.; Gambhir, Sanjiv S.; Wu, Anna M.

2014-01-01

271

Animal models of atherosclerosis  

PubMed Central

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. PMID:24868511

Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

2014-01-01

272

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.

273

Model animals for the study of oxidative stress from complex II.  

PubMed

Mitochondria play a role of energy production and produce intracellular reactive oxygen species (ROS), especially superoxide anion (O2(-)) as a byproduct of energy metabolism at the same time. O2(-) is converted from oxygen and is overproduced by excessive electron leakage from the mitochondrial respiratory chain. It is well known that mitochondrial complexes I and III in the electron transport system are the major endogenous ROS sources. We have previously demonstrated that mutations in complex II can result in excessive ROS (specifically in SDHC: G71E in Caenorhabditis elegans, I71E in Drosophila and V69E in mouse). Moreover, this results in premature death in C. elegans and Drosophila as well as tumorigenesis in mouse embryonic fibroblast cells. In humans, it has been reported that mutations in SDHB, SDHC or SDHD, which are the subunits of mitochondrial complex II, often result in inherited head and neck paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic mice using our uniquely developed Tet-On/Off system, which can induce the mutated SDHC gene to be equally and competitively expressed compared to the endogenous wild-type SDHC gene. These mice experienced mitochondrial respiratory chain dysfunction that resulted in oxidative stress. The mitochondrial oxidative stress caused excessive apoptosis in several tissues leading to low-birth-weight infants and growth retardation during neonatal developmental phase in Tet-mev-1 mice. Tet-mev-1 mice also displayed precocious age-dependent corneal physiological changes, delayed corneal epithelialization, decreased corneal endothelial cells, thickened Descemet's membrane and thinning of parenchyma with corneal pathological dysfunctions such as keratitis, Fuchs' corneal dystrophy (FCD) and probably keratoconus after the normal development and growth phase. Here, we review the relationships between mitochondrial oxidative stress and phenomena in mev-1 animal models with mitochondrial complex II SDHC mutations. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. PMID:23142169

Ishii, Takamasa; Miyazawa, Masaki; Onouchi, Hiromi; Yasuda, Kayo; Hartman, Phil S; Ishii, Naoaki

2013-05-01

274

A Review of Hazardous Chemical Toxicity Studies Utilizing Genetically-Modified Animals-Their Applications for Risk Assessment  

Microsoft Academic Search

Studies on the mechanisms of chemical toxicity carried out using knockout mice lacking genes of enzymes for drug metabolism or nuclear receptor proteins were reviewed, and the studies were compared with the respective conventional mechanistic studies. While the toxicity of many hazardous chemicals was observed only in wild-type or knockout mice, which clearly showed that their toxicity was involved in

Tamie NAKAJIMA; Rui-Sheng WANG; Yuki ITO; Toshifumi AOYAMA; Michihiro KAMIJIMA

2005-01-01

275

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)

2011-12-08

276

Beneficial Effect of Food Substitute Containing L-Arginine, ?-3 Poly Unsaturated Fatty Acid, and Ribonucleic Acid in Preventing or Improving Metabolic Syndrome: A Study in 15 Overweight Patients and a Study of Fatty Acid Metabolism in Animals  

PubMed Central

This study was conducted to investigate whether or not a food substitute (Dr. BAANs®) containing three bioactive components L-arginine, ?-3 polyunsaturated fatty acid, and ribonucleic acid, supplied orally to 15 overweight patients, may have efficacy to prevent or improve the metabolic syndrome of these patients. To provide supporting data for this clinical study, the in vivo fatty acid metabolism of obese mice was analyzed using 125I labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA) in the tissues’ lipid pool. After 3 months of intervention, the results showed that there were improvements observed in liver functions, lipid profiles and metabolic syndrome marker. Significant differences were also found in the values of blood pressure, body weight, percentage of body fat, and body mass index. In the animal study, the tissue uptake of 125I-9MPA at 10 min after injection was higher in obese mice than in the control mice and the treatment with Dr. BAANs® in obese mice decreased the uptake significantly. The final product metabolite of p-iodophenylacetic acid in obese mice was increased significantly by the treatment. In conclusion, this food substitute may have a beneficial effect for the prevention or improvement of metabolic syndrome. PMID:19430616

Watanabe, Kenichi; Arozal, Wawaimuli; Tanaka, Hiroko; Ma, Meilei; Satoh, Susumu; Veeraveedu, Punniyakoti T.; Kobayashi, Takashi; Oyama, Hiroshi; Sakaguchi, Yoshiko

2009-01-01

277

NIH Researchers Find Resveratrol Helps Protect against Cardiovascular Disease in Animal Study  

MedlinePLUS

NIH researchers find Resveratrol helps protect against cardiovascular disease in animal study June 3, 2014 Resveratrol, a compound found in nuts, grapes, and wine, may protect against certain cardiovascular problems, according to ...

278

Keeping two animal systems in one lab – a frog plus fish case study  

E-print Network

For two decades, my lab has been studying development using two vertebrate animals, the frog Xenopus and the zebrafish, Danio. This has been both productive and challenging. The initial rationale for the choice was to ...

Sive, Hazel L.

2011-01-01

279

Contribution of animal studies to evaluate the similarity of biosimilars to reference products.  

PubMed

The European Union (EU) was the first region to establish a regulatory framework for biosimilars, in which animal studies are required to confirm similarity to a reference product. However, animal studies described in European public assessment reports (EPARs) or marketing authorisation applications (MAAs) did not identify clinically or toxicologically relevant differences despite differences in quality, suggesting that animal studies lack the sensitivity to confirm biosimilarity. Scientific advice provided learning opportunities to evolve existing guidance. Altogether, the data support a step-wise approach to develop biosimilars that focuses on quality and clinical efficacy of biosimilar. This approach might be more effective and does not necessarily require animal studies, which is also reflected in new EU draft guidance. PMID:25463036

van Meer, Peter J K; Ebbers, Hans C; Kooijman, Marlous; Wied, Christine C Gispen-de; Silva-Lima, Beatriz; Moors, Ellen H M; Schellekens, Huub

2014-11-20

280

INTRODUCTION The study of animal movement patterns allows us to  

E-print Network

. A case study with Eagle Owls Bubo bubo Delgado M.M., Penteriani V. & Nams V.O. 2009. How fledglings explore sur- roundings from fledging to dispersal. A case study with Eagle Owls Bubo bubo. Ardea 97(1): 7 Owls Bubo bubo during the post-fledging dependence period (1962 locations from 41 tagged owlets

Penteriani, Vincenzo

281

Comparative gavage subchronic toxicity studies of o-chloroaniline and m-chloroaniline in F344 rats and B6C3F1 mice.  

PubMed

ortho-Chloroaniline (o-CA) andmeta-chloroaniline (m-CA) are chemical intermediates for pigment production in the textile industry. Comparative subchronic gavage studies were conducted to determine the effect of structure on toxicity.o-CA orm-CA was administered to 10 animals/sex/species in deionized water at dosages of 0, 10, 20, 40, 80, and 160 mg/kg for 13 weeks. Blood samples for clinical pathology were collected after 3 and 23 days in rats and at study termination (Day 93) in rats and mice. No mortalities occurred that could be directly attributed to treatment. Transient clinical signs of toxicity observed after dosing included cyanosis in rats and ataxia and tremors in mice. Methemoglobin formation was directly related to dosage (rats and mice) and duration of treatment (rats). At study termination, Heinz body formation in erythrocytes in association with decreased hemoglobin, hematocrit, and red blood cell count was a prominent treatment-related effect. Enlarged spleens (gross necropsy observation) and increased spleen weight were treatment effects of each chemical in both species. Microscopic lesions typical of increased red blood cell production were found in hematopoietic tissues (bone marrow, spleen, and liver), while lesions due to increased red cell destruction were found in these tissues and also the kidneys (rats). Microscopic changes were more frequently seen and severe, and involved more body organs, in rats than mice, and in m-CA-treated animals thano-CA-treated animals. Sex differences in lesion incidence/severity were not evident. PMID:12215679

Hejtmancik, M R; Trela, B A; Kurtz, P J; Persing, R L; Ryan, M J; Yarrington, J T; Chhabra, R S

2002-09-01

282

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

PubMed Central

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. PMID:24936425

Nathoo, Nabeela; Yong, V. Wee; Dunn, Jeff F.

2014-01-01

283

Guidelines for Endpoints in Animal Study Proposals Introduction  

E-print Network

, smaller pilot studies may be useful as they can be instrumental to the development of an appropriate are not prominent/visible, palpable with slight pressure BC 4 - Over conditioned ­ spine is a continuous column

Bandettini, Peter A.

284

DIESEL PARTICLE GENERATION, CHARACTERIZATION, AND DIRECT ANIMAL EXPOSURE STUDIES  

EPA Science Inventory

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...

285

Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.  

PubMed

Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications. PMID:22690908

Demiro?lu, Hasan; Avciba?i, Ugur; Ünak, Perihan; Müftüler, Fazilet Zümrüt Biber; ?çhedef, Ç A; Gümü?er, Fikriye Gül; Sakarya, Serhan

2012-08-01

286

Fabry Disease: Preclinical Studies Demonstrate the Effectiveness of ?-Galactosidase A Replacement in Enzyme-Deficient Mice  

PubMed Central

Preclinical studies of enzyme-replacement therapy for Fabry disease (deficient ?-galactosidase A [?-Gal A] activity) were performed in ?-Gal A–deficient mice. The pharmacokinetics and biodistributions were determined for four recombinant human ?-Gal A glycoforms, which differed in sialic acid and mannose-6-phosphate content. The plasma half-lives of the glycoforms were ?2–5 min, with the more sialylated glycoforms circulating longer. After intravenous doses of 1 or 10 mg/kg body weight were administered, each glycoform was primarily recovered in the liver, with detectable activity in other tissues but not in the brain. Normal or greater activity levels were reconstituted in various tissues after repeated doses (10 mg/kg every other day for eight doses) of the highly sialylated AGA-1 glycoform; 4 d later, enzyme activity was retained in the liver and spleen at levels that were, respectively, 30% and 10% of that recovered 1 h postinjection. Importantly, the globotriaosylceramide (GL-3) substrate was depleted in various tissues and plasma in a dose-dependent manner. A single or repeated doses (every 48 h for eight doses) of AGA-1 at 0.3–10.0 mg/kg cleared hepatic GL-3, whereas higher doses were required for depletion of GL-3 in other tissues. After a single dose of 3 mg/kg, hepatic GL-3 was cleared for ?4 wk, whereas cardiac and splenic GL-3 reaccumulated at 3 wk to ?30% and ?10% of pretreatment levels, respectively. Ultrastructural studies demonstrated reduced GL-3 storage posttreatment. These preclinical animal studies demonstrate the dose-dependent clearance of tissue and plasma GL-3 by administered ?-Gal A, thereby providing the in vivo rationale—and the critical pharmacokinetic and pharmacodynamic data—for the design of enzyme-replacement trials in patients with Fabry disease. PMID:11115376

Ioannou, Yiannis A.; Zeidner, Ken M.; Gordon, Ronald E.; Desnick, Robert J.

2001-01-01

287

Ethical considerations and animal welfare in ecological field studies  

Microsoft Academic Search

This paper addresses some of the ethical and welfare considerations implicit in the application of general techniques in common use during the course of collecting data in ecological field work. Even if they are not explicitly constructed as manipulative experiments, many field studies involve some degree of intervention during routine monitoring programmes: through disturbance caused merely by the presence of

R. J. Putman

1995-01-01

288

FURTHER STUDIES ON TRYPANOSOMES IN GAME ANIMALS IN WYOMING 1100  

Microsoft Academic Search

Further studies on moose revealed trypanosomes in two captive moose (Alces alces shirasi) and in 4 of 7 free-ranging moose in Wyoming by blood culture. Two free-ranging moose from Utah were negative. One of two additional captive moose calves was positive for trypanosomes. Trypanosomes also were detected in blood cultures of 8 of 39 American bison (Bison bison) being brought

NEWTON KINGSTON; E. TOM; GEORGE M. THOMAS; B LINDA McHOLLANDand; MALCOLM S. TRUEBLOOD

289

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

PubMed

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40 % decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200 % increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging. PMID:25430587

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

2015-01-01

290

Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed to functionalized multi-walled carbon nanotubes  

PubMed Central

Carbon nanotubes (CNTs), the most promising material with unique characteristics, find its application in different fields ranging from composite materials to medicine and from electronics to energy storage. However, little is known about the mechanisms behind the interaction of these particles with cells and their toxicity. The aim of this study was to assess the effects, after intraperitoneal injection, of functionalized multi walled carbon nanotubes (MWCNT) (carboxyl groups) on various hepatotoxicity and oxidative stress biomarkers (ROS, LHP, ALT, AST, ALP and morphology of liver) in the mouse model. The mice were dosed intraperitoneally at 0.25, 0.5 & 0.75 mg/kg/day for 5 days of purified/functionalized MWCNTs and two controls (negative; saline and positive; carbon black 0.75 mg/kg) as appropriate. Samples were collected 24 hours after the fifth day treatment following standard protocols. Exposure to carboxylated functionalized MWCNT; the body-weight gain of the mice decreased, induced reactive oxygen species (ROS), and enhanced the activities of serum amino-transferases (ALT/AST), alkaline phosphatases (ALP) and concentration of lipid hydro peroxide compared to control. Histopathology of exposed liver showed a statistically significant effect in the morphological alterations of the tissue compared to controls. The cellular findings reported here do suggest that purified carboxylated functionalized MWCNT has the potential to induce hepatotoxicity in Swiss-Webster mice through activation of the mechanisms of oxidative stress, which warrant in vivo animal exposure studies. However, more studies of functionalization in the in vivo toxicity of MWCNTs are required and parallel comparison is preferred. PMID:21725842

Patlolla, Anita K.; Berry, Ashley; Tchounwou, Paul B.

2013-01-01

291

Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate.  

PubMed

Methylene blue trihydrate is used widely as a dye and therapeutic agent. Methylene blue was administered by gavage to 30 animals/sex/dose group in a 0.5% aqueous methylcellulose suspension at doses of 0, 25, 50, 100, and 200 mg/kg. Blood samples from 10 animals/sex/dose group were collected at the end of study weeks 1, 6, and 13. Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. There was a dose-related increase in absolute and relative spleen weight for both species. Microscopic examination revealed increased splenic hematopoiesis in all mice treatment groups and in rats at the 50 mg/kg dose level and above. Splenic congestion and bone marrow hyperplasia were also observed in these rat-dose groups. Mice at the higher doses showed hematopoiesis in the liver and accumulation of hemosiderin in Kupffer cells. These gross and microscopic findings are consistent with the development of hemolytic anemia. A dose-related increase in the reticulocyte count during study weeks 6 and 13 suggested a compensatory response to anemia. PMID:11752692

Hejtmancik, M R; Ryan, M J; Toft, J D; Persing, R L; Kurtz, P J; Chhabra, R S

2002-01-01

292

Nanocrystalline hydroxyapatite for bone repair: an animal study  

Microsoft Academic Search

Hydroxyapatite has become the most common material to replace bone or to guide its regeneration. Nanocrystalline hydroxyapatite\\u000a suspension had been introduced in the clinical use recently under the assumption that small dimension of crystals could improve\\u000a resorption. We studied the resorption and osteointegration of the nanocrystalline hydroxyapatite Ostim® in a rabbit model. The material was implanted either alone or in

J. BrandtS; S. Henning; G. Michler; W. Hein; A. Bernstein; M. Schulz

2010-01-01

293

Osteoarthritis pain mechanisms: Basic studies in animal models  

PubMed Central

Osteoarthritis (OA) is a complex and painful disease of the whole joint. At present there are no satisfying agents for treating OA. The current standard of care mainly involves managing and alleviating its symptoms. Mechanisms of OA pain have been studied in rodent knee OA models produced by intra-knee injection of the chondrocyte glycolytic inhibitor mono-iodoacetate, surgery, or spontaneous development in some species. These models are clinically relevant in terms of histological damage and functional changes, and are used to study mechanisms underlying mechanical, thermal, ambulatory, body weight supporting-evoked, and ongoing OA pain. Recent peripheral, spinal, and supraspinal biochemical and electrophysiological studies in these models suggest that peripheral pro-inflammatory mediators and neuropeptides sensitize knee nociceptors. Spinal cytokines and neuropeptides promote OA-associated pain, and peripheral and spinal cannabinoids inhibit OA pain respectively through cannabinoid-1 (CB1) and CB1/CB2 receptors. TRPV1 and metalloproteinases contribute and supraspinal descending facilitation of 5-HT/5-HT 3 receptors may also contribute to OA pain. Conditioned place preference tests demonstrate that OA pain induces aversive behaviors suggesting brain involvement in OA pain. During OA, brain functional connectivity is enhanced, but at present it is unclear how this change is related to OA pain. PMID:23973145

Zhang, Rui-Xin; Ren, Ke; Dubner, Ronald

2013-01-01

294

Goldfish, Carassius auratus, a Novel Animal Model for the Study of Mycobacterium marinum Pathogenesis  

PubMed Central

We have developed an animal model for studying mycobacterial pathogenesis using Mycobacterium marinum and the goldfish, Carassius auratus. Goldfish are injected intraperitoneally with doses between 102 and 109 CFU of M. marinum organisms. Depending on the dose of M. marinum organisms administered, an acute or chronic disease is produced. The acute disease is characterized by systemic mycobacterial infection, severe peritonitis, tissue necrosis, and a short median survival time. The chronic disease is characterized by granuloma formation in all organs and survival of animals to the end point of the experiment (56 days). Colony counts in organ homogenates showed recovery of mycobacteria from a high percentage of inoculated animals. We believe this well-characterized animal model will be useful for studying mycobacterial pathogenesis. PMID:9596770

Talaat, Adel M.; Reimschuessel, Renate; Wasserman, Steven S.; Trucksis, Michele

1998-01-01

295

Liposomes-in-Hydrogel Delivery System with Mupirocin: In Vitro Antibiofilm Studies and In Vivo Evaluation in Mice Burn Model  

PubMed Central

Previously, we have proposed mupirocin-in-liposomes-in-hydrogel delivery system as advanced delivery system with the potential in treatment of burns. In the current studies, we evaluated the system for its cytotoxicity, ability to prevent biofilm formation, act on the mature biofilms, and finally determined its potential as wound treatment in in vivo mice burn model. The system was found to be nontoxic against HaCaT cells, that is, keratinocytes. It was safe for use and exhibited antibiofilm activity against S. aureus biofilms, although the activity was more significant against planktonic bacteria and prior to biofilm formation than against mature biofilms as shown in the resazurin and the crystal violet assays. An in vivo mice burn model was used to evaluate the biological potential of the system and the healing of burns observed over 28 days. The in vivo data suggest that the delivery system enhances wound healing and is equally potent as the marketed product of mupirocin. Histological examination showed no difference in the quality of the healed scar tissue, whereas the healing time for the new delivery system was shorter as compared to the marketed product. Further animal studies and development of more sophisticated in vivo model are needed for complete evaluation. PMID:24369533

Hurler, Julia; Sørensen, Karen K.; Vuorela, Pia; Škalko-Basnet, Nataša

2013-01-01

296

Animal models of asthma.  

PubMed

Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma. PMID:17581191

Zosky, G R; Sly, P D

2007-07-01

297

Postmortem absorption of dichloromethane: a case study and animal experiments.  

PubMed

A case of accidental death after occupational exposure to an atmosphere containing dichloromethane (DCM) is reported. The concentrations of DCM in the blood and tissues of a 40-year-old man who died while observing an industrial washing machine filled with DCM vapour were blood 1660 mg/l, urine 247 mg/l, brain 87 mg/kg, heart muscle 199 mg/kg and lungs 103 mg/kg which are 3-7 times higher than previously reported fatal levels. The body was left undiscovered in the machine filled with DCM vapour for about 20 h. The present study was designed to determine whether all the DCM detected in the tissues and body fluids had been inhaled while alive using rats as the experimental model. The concentrations of DCM in the tissues and body fluids of a rat that died from DCM poisoning and was left for 20 h in a box containing DCM vapour were the same as those in the tissues and body fluids of a rat that had died from an injected overdose of barbiturates and had then been placed in the DCM box in a similar manner. Moreover, the concentrations of DCM in the tissues and body fluids of the carcasses that were exposed to the DCM vapour increased gradually throughout the period of exposure. These findings imply that DCM is able to penetrate the tissues and body fluids of rat carcasses through a route other than inhalation such as through the skin. PMID:11197638

Takeshita, H; Mogi, K; Yasuda, T; Mori, S; Nakashima, Y; Nakajima, T; Akuzawa, H; Nakajo, S; Hirota, Y; Kishi, K

2000-01-01

298

Cannabinoids and gastrointestinal motility: animal and human studies.  

PubMed

The plant Cannabis has been known for centuries to be beneficial in a variety of gastrointestinal diseases, including emesis, diarrhea, inflammatory bowel disease and intestinal pain. delta9-tetrahydrocannabinol, the main psychotropic component of Cannabis, acts via at least two types of cannabinoid receptors, named CB1 and CB2 receptors. CB1 receptors are located primarily on central and peripheral neurons (including the enteric nervous system) where they modulate neurotransmitter release, whereas CB2 receptors are concerned with immune function, inflammation and pain. The discovery of endogenous ligands [i.e. anandamide and 2-arachidonoyl glycerol (2-AG)] for these receptors indicates the presence of a functional endogenous cannabinoid system in the gastrointestinal tract. Anatomical and functional evidence suggests the presence of CB1 receptors in the myenteric plexus, which are associated with cholinergic neurons in a variety of species, including in humans. Activation of prejunctional CB1 receptors reduces excitatory enteric transmission (mainly cholinergic transmission) in different regions of the gastrointestinal tract. Consistently, in vivo studies have shown that cannabinoids reduce gastrointestinal transit in rodents through activation of CB1, but not CB2, receptors. However, in pathophysiological states, both CB1 and CB2 receptors could reduce the increase of intestinal motility induced by inflammatory stimuli. Cannabinoids also reduce gastrointestinal motility in randomized clinical trials. Overall, modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility. PMID:18924447

Aviello, G; Romano, B; Izzo, A A

2008-08-01

299

Regression of Atherosclerosis: Insights from Animal and Clinical Studies  

PubMed Central

Based on studies that extend back to the 1920s, regression and stabilization of atherosclerosis in humans has gone from just a dream to one that is achievable. Review of the literature indicates that the successful attempts at regression generally applied robust measures to improve plasma lipoprotein profiles. Examples include extensive lowering of plasma concentrations of atherogenic apolipoprotein B and enhancement of reverse cholesterol transport from atheromata to the liver. Possible mechanisms responsible for lesion shrinkage include decreased retention of atherogenic apolipoprotein B within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of lesional foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris as well as other components of the plaque. However, currently available clinical agents cause less dramatic changes in plasma lipoprotein levels, and thereby fail to stop most cardiovascular events. There is, therefore, a clear need for preclinical and clinical testing of new agents expected to facilitate atherosclerosis regression with the hope that additional mechanistic insights will allow further progress. PMID:24751561

Feig, Jonathan E.

2014-01-01

300

Further studies on trypanosomes in game animals in Wyoming II.  

PubMed

Further studies on moose revealed trypanosomes in two captive moose (Alces alces shirasi) and in 4 of 7 free-ranging moose in Wyoming by blood culture. Two free-ranging moose from Utah were negative. One of two additional captive moose calves was positive for trypanosomes. Trypanosomes also were detected in blood cultures of 8 of 39 American Bison (Bison bison) being brought into Wyoming from Nebraska. Nineteen additional bison were negative for trypanosomes by blood cultures. Identification of species was not possible due to the failure to obtain bloodstream trypomastigotes from this host. Trypanosomes were recovered from 8 of 57 pronghorn antelope (Antilocapra americana). This is the first report of Trypanosoma sp. from bison and from pronghorn; the trypanosome from moose was identified as Trypanosoma cervi from bloodstream trypomastigotes. In 1978, natural transplacental transmission of trypanosomes was found to occur in 1 of 15 mule deer (Odocoileus hemionus) fetuses, examined near term by blood culture. No trypanosomes were found in 18 male deer fetuses examined in 1979. Of 100 free-ranging elk from western Wyoming examined by blood culture in 1979, 71 were infected. These data are compared with data from 1973-74. PMID:7338978

Kingston, N; Thorne, E T; Thomas, G M; McHolland, L; Trueblood, M S

1981-10-01

301

Carcinogenicity studies of diesel engine exhausts in laboratory animals: a review of past studies and a discussion of future research needs.  

PubMed

Diesel engines play a vital role in world economy, especially in transportation. Exhaust from traditional diesel engines using high-sulfur fuel contains high concentrations of respirable carbonaceous particles with absorbed organic compounds. Recognition that some of these compounds are mutagenic has raised concern for the cancer-causing potential of diesel exhaust exposure. Extensive research addressing this issue has been conducted during the last three decades. This critical review is offered to facilitate an updated assessment of the carcinogenicity of diesel exhaust and to provide a rationale for future animal research of new diesel technology. Life-span bioassays in rats, mice, and Syrian hamsters demonstrated that chronic inhalation of high concentrations of diesel exhaust caused lung tumors in rats but not in mice or Syrian hamsters. In 1989, the International Agency for Research on Cancer (IARC) characterized the rat findings as "sufficient evidence of animal carcinogenicity," and, with "limited" evidence from epidemiological studies, classified diesel exhaust Category 2A, a "probable human carcinogen." Subsequent research has shown that similar chronic high concentration exposure to particulate matter generally considered innocuous (such as carbon black and titanium dioxide) also caused lung tumors in rats. Thus, in 2002, the U.S. Environmental Protection Agency (EPA) concluded that the findings in the rats should not be used to characterize the cancer hazard or quantify the cancer risk of diesel exhaust. Concurrent with the conduct of the health effects studies, progressively more stringent standards have been promulgated for diesel exhaust particles and NOx. Engine manufacturers have responded with new technology diesel (improved engines, fuel injection, fuels, lubricants, and exhaust treatments) to meet the standards. This review concludes with an outline of research to evaluate the health effects of the new technology, research that is consistent with recommendations included in the U.S. EPA 2002 health assessment document. When this research has been completed, it will be appropriate for IARC to evaluate the potential cancer hazard of the new technology diesel. PMID:16097136

Hesterberg, Thomas W; Bunn, William B; McClellan, Roger O; Hart, Georgia A; Lapin, Charles A

2005-06-01

302

Animal studies in spinal cord injury: a systematic review of methylprednisolone.  

PubMed

The objective of this study was to examine whether animal studies can reliably be used to determine the usefulness of methylprednisolone (MP) and other treatments for acute spinal cord injury (SCI) in humans. This was achieved by performing a systematic review of animal studies on the effects of MP administration on the functional outcome of acute SCI. Data were extracted from the published articles relating to: outcome; MP dosing regimen; species/strain; number of animals; methodological quality; type of injury induction; use of anaesthesia; functional scale used; and duration of follow-up. Subgroup analyses were performed, based on species or strain, injury method, MP dosing regimen, functional outcome measured, and methodological quality. Sixty-two studies were included, which involved a wide variety of animal species and strains. Overall, beneficial effects of MP administration were obtained in 34% of the studies, no effects in 58%, and mixed results in 8%. The results were inconsistent both among and within species, even when attempts were made to detect any patterns in the results through subgroup analyses. The results of this study demonstrate the barriers to the accurate prediction from animal studies of the effectiveness of MP in the treatment of acute SCI in humans. This underscores the need for the development and implementation of validated testing methods. PMID:19292575

Akhtar, Aysha Z; Pippin, John J; Sandusky, Chad B

2009-02-01

303

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study  

NASA Astrophysics Data System (ADS)

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ˜3 s and ˜9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.

Mahmoud, Ahmed M.; Ding, Xuan; Dutta, Debaditya; Singh, Vijay P.; Kim, Kang

2014-02-01

304

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study.  

PubMed

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ? 3 s and ? 9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis. PMID:24487698

Mahmoud, Ahmed M; Ding, Xuan; Dutta, Debaditya; Singh, Vijay P; Kim, Kang

2014-02-21

305

Fermentation of animal components in strict carnivores: a comparative study with cheetah fecal inoculum.  

PubMed

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

2012-08-01

306

Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice  

PubMed Central

Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 102, 103 and 104 organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 103 and 104 B. pseudomallei cells, animals infected with 102 organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections. PMID:24098563

Lafontaine, Eric R.; Zimmerman, Shawn M.; Shaffer, Teresa L.; Michel, Frank; Gao, Xiudan; Hogan, Robert J.

2013-01-01

307

A New Animal Model to Study Intimal Hyperplasia in Arteriovenous Fistulas  

Microsoft Academic Search

Background. Intimal hyperplasia (IH) plays a key role in the failure of arteriovenous (AV) fistulas. The animal models available to study IH in AV fistulas are expensive and do not mimic the development of truly stenotic IH. In this study we examined whether goats are a more suitable model to study IH in AV fistulas.Materials and Methods. Thirteen direct and

M. S. Lemson; M. J. A. P. Daemen; J. H. M. Tordoir

1999-01-01

308

Euthanasia of neonatal mice with carbon dioxide  

USGS Publications Warehouse

Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

2005-01-01

309

Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity.  

PubMed

Laboratory animal models have provided valuable insight into foot-and-mouth disease virus (FMDV) pathogenesis in epidemiologically important target species. While not perfect, these models have delivered an accelerated time frame to characterize the immune responses in natural hosts and a platform to evaluate therapeutics and vaccine candidates at a reduced cost. Further expansion of these models in mice has allowed access to genetic mutations not available for target species, providing a powerful and versatile experimental system to interrogate the immune response to FMDV and to target more expensive studies in natural hosts. The purpose of this review is to describe commonly used FMDV infection models in laboratory animals and to cite examples of when these models have failed or successfully provided insight relevant for target species, with an emphasis on natural and vaccine-induced immunity. PMID:25000962

Habiela, Mohammed; Seago, Julian; Perez-Martin, Eva; Waters, Ryan; Windsor, Miriam; Salguero, Francisco J; Wood, James; Charleston, Bryan; Juleff, Nicholas

2014-11-01

310

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology  

PubMed Central

The rodent hippocampal slice preparation is perhaps the most broadly used tool for investigating mammalian synaptic function and plasticity. The hippocampus can be extracted quickly and easily from rats and mice and slices remain viable for hours in oxygenated artificial cerebrospinal fluid. Moreover, basic electrophysisologic techniques are easily applied to the investigation of synaptic function in hippocampal slices and have provided some of the best biomarkers for cognitive impairments. The hippocampal slice is especially popular for the study of synaptic plasticity mechanisms involved in learning and memory. Changes in the induction of long-term potentiation and depression (LTP and LTD) of synaptic efficacy in hippocampal slices (or lack thereof) are frequently used to describe the neurologic phenotype of cognitively-impaired animals and/or to evaluate the mechanism of action of nootropic compounds. This article outlines the procedures we use for preparing hippocampal slices from rats and transgenic mice for the study of synaptic alterations associated with brain aging and Alzheimer's disease (AD)1-3. Use of aged rats and AD model mice can present a unique set of challenges to researchers accustomed to using younger rats and/or mice in their research. Aged rats have thicker skulls and tougher connective tissue than younger rats and mice, which can delay brain extraction and/or dissection and consequently negate or exaggerate real age-differences in synaptic function and plasticity. Aging and amyloid pathology may also exacerbate hippocampal damage sustained during the dissection procedure, again complicating any inferences drawn from physiologic assessment. Here, we discuss the steps taken during the dissection procedure to minimize these problems. Examples of synaptic responses acquired in "healthy" and "unhealthy" slices from rats and mice are provided, as well as representative synaptic plasticity experiments. The possible impact of other methodological factors on synaptic function in these animal models (e.g. recording solution components, stimulation parameters) are also discussed. While the focus of this article is on the use of aged rats and transgenic mice, novices to slice physiology should find enough detail here to get started on their own studies, using a variety of rodent models. PMID:21490565

Mathis, Diana M.; Furman, Jennifer L.; Norris, Christopher M.

2011-01-01

311

Tolerability and toxicological profile of pixantrone (Pixuvri®) in juvenile mice. Comparative study with doxorubicin.  

PubMed

The tolerability of pixantrone dimaleate (Pixuvri(®)), an aza-anthracenedione for non-Hodgkin lymphoma, was assessed in juvenile mice after intraperitoneal injection. Twenty animals/sex/dose received pixantrone 15 or 27 mg/kg/day on Post-Natal-Days (PND) 10, 13, 17, 20, 35, 39 and 42 in comparison with doxorubicin, 3 mg/kg/day. Animals were sacrificed on PND 42, 73 and 96. All pixantrone animals survived, while doxorubicin induced 52.5% mortality and the surviving animals were sacrificed early due to severe toxicity. Recoverable bone marrow toxicity (pixantrone), and toxicity to thymus and reproductive organs (pixantrone, doxorubicin) were observed without nephro- or hepatotoxicity. Pixantrone was measurable in plasma up to 2h (occasionally 6h) post-dose. At PND 42, mean Cmax and AUC values increased proportionally with dose, without gender difference or accumulation. Pixantrone showed minimal cardiotoxicity in males and negligible in females at PND 96. Doxorubicin induced significant heart weight reduction at PND 42, however early sacrifice impeded further cardiac assessments. PMID:24602559

Longo, Monica; Della Torre, Paola; Allievi, Cecilia; Morisetti, Alberto; Al-Fayoumi, Suliman; Singer, Jack W

2014-07-01

312

Histopathological studies of acute and chronic effects of Calliandra portoricensis leaf extract on the stomach and pancreas of adult Swiss albino mice  

PubMed Central

Objective To evaluate the consequence of oral administration of Calliandra portoricensis (C. portoricensis) leaf extract on the stomach and pancreas in Swiss albino mice. Methods Three groups of mice (B, C and D) were treated with 4 mg/kg of C. portoricensis extract. Group A was the control and received an equivalent volume of distilled water. Group B received C. portoricensis leaf extract for 7 days, Group C received C. portoricensis leaf extract for 14 days, and Group D received C. portoricensis leaf extract for 28 days. At different stages in the study, the mice were sacrificed and the stomach and pancreas were excised and fixed in 10% formol saline for histological analysis. Results The result showed a normal microstructural outline in groups B and C as compared with the control. However, animals in group D showed disorganization of the mucosa and discontinuation of epithelial lining of the stomach while the islets of Langerans in the pancreas were at various degree of degeneration as compared with the control mice. Conclusions The present finding suggests that chronic administration (28 days as seen in this study) of C. portoricensis leaf extract may inhibit the proper function of the stomach and pancreas. PMID:23569755

Ofusori, David A; Adejuwon, Adebomi O

2011-01-01

313

Do studies in caveolin-knockouts teach us about physiology and pharmacology or instead, the ways mice compensate for ‘lost proteins'?  

PubMed Central

A wide array of phenotypic changes have been reported in mice with knockout of expression of caveolin-1. Neidhold et al. (2007) describe results in this issue that continue this trend by showing that saphenous arteries from adult caveolin-1 knockout mice lack caveolae, lose ?1-adrenoceptor-promoted relaxation, gain ?3-adrenoceptor-promoted relaxation but show no change in vasomotor response to ?2-adrenoceptor activation. Neither the physiological importance for wild-type animals nor the mechanistic basis for these changes is clear. Although the caveolin-1 knockout and wild-type mice express similar levels of the receptor mRNAs, the protein expression of the receptors is not specified and represents, in our view, an important limitation of the study. We also question the physiological relevance of the findings and ask: Do studies in total body/lifespan caveolin-knockout mice further understanding of physiology and pharmacology or do they primarily characterize secondary consequences? We propose that alternative approaches that decrease caveolin expression in a temporally and spatially discrete manner are more likely to facilitate definitive conclusions regarding caveolin-1 and its role in regulation of ?-adrenoceptors and other pharmacological targets. PMID:17179949

Insel, P A; Patel, H H

2006-01-01

314

PSYCHOPHARMACOLOGY OF DOPAMINE: THE CONTRIBUTION OF COMPARATIVE STUDIES IN INBRED STRAINS OF MICE  

Microsoft Academic Search

Comparative studies of behavioral responses to centrally acting drugs in inbred strains of mice which show differences in brain neurotransmitter activity represent a major strategy in the investigation of the neurochemical bases underlying behavioral expression. Moreover, these studies represent a preliminary stage in behavioral genetic research since they allow quantitative scales to be established and suggest correlations to be tested

STEFANO PUGLISI-ALLEGRA; SIMONA CABIB

1997-01-01

315

Immunological studies on mice exposed subacutely to methyl isocyanate  

SciTech Connect

The immunotoxicity of methyl isocyanate (MIC) was evaluated in female B6C3F1 mice exposed via inhalation to 0, 1, or 3 ppm for 6 hr per day on 4 consecutive days. The antibody response to sheep erythrocytes and natural killer cell activity were found to be unaffected by MIC exposure. Although lymphoproliferative responses to mitogens were moderately suppressed by MIC, the differences were not statistically significant. The response of splenic lymphocytes to allogeneic leukocytes in a mixed leukocyte response (MLR) was suppressed in a dose-related fashion and was significantly different from the control response at the 3 ppm level. This effect was thought to be secondary and a result of general toxicity rather than a direct effect of MIC on the immune system. Furthermore, resistance to the infectious agents Listeria monocytogenes, mouse malaria parasite, and influenza virus, or to transplantable tumor cells was not compromised by MIC exposure. Thus, the immune system does not appear to be a primary target for MIC toxicity.

Tucker, A.N.; Bucher, J.R.; Germolec, D.R.; Silver, M.T.; Vore, S.J.; Luster, M.I.

1987-06-01

316

Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases  

PubMed Central

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. PMID:23874156

Sena, Emily S.; Aretouli, Eleni; Evangelou, Evangelos; Howells, David W.; Salman, Rustam Al-Shahi; Macleod, Malcolm R.; Ioannidis, John P. A.

2013-01-01

317

STUDIES OF THE MECHANISM OF ACTION OF URETHANE IN INITIATING PULMONARY ADENOMAS IN MICE  

PubMed Central

The process of carcinogenesis following exposure of mice to urethane is demonstrated in the present work to be intimately related to nucleic acid synthesis. Injection of animals with a DNA hydrolysate immediately prior to a single exposure of the animals to urethane markedly reduced the number of pulmonary adenomas initiated. Aminopterin, known to interfere in nucleic acid synthesis (46), potentiated the carcinogenic action of urethane and this potentiation was blocked by injection of a DNA hydrolysate. Of the components and precursors of nucleic acids the pyrimidine series seemed especially concerned. Alterations in the utilization of oxaloacetate, ureidosuccinic acid, dihydro-orotic acid, orotic acid, cytidylic acid, and thymine appeared to be critical steps in the oncogenic process, following upon the primary disorder of cellular metabolism initiated by the carcinogen. All these substances except oxaloacetate profoundly reduced the number of tumors initiated by urethane. Oxaloacetate potentiated the carcinogenic effect. When these results are viewed together and in relation to known facts concerning nucleic acid synthesis they provide evidence suggesting that the point of action of the carcinogen is in the pathway of nucleic acid synthesis below orotic acid and perhaps at the level of ureidosuccinic acid. The potentiating influence of adenine, 4-amino-5-imidazole carboxamide, and aminopterin, the lack of effect of uracil, and the inhibitory influence of thymine together suggest that DNA rather than RNA is the nucleic acid critical to the oncogenic response of mice to urethane. PMID:13416469

Rogers, Stanfield

1957-01-01

318

Comparative studies of the effects of Tabebuia avellanedae bark extract and beta-lapachone on the hematopoietic response of tumour-bearing mice.  

PubMed

The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg) and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of beta-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and beta-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development. PMID:18343063

Queiroz, Mary L S; Valadares, Marize C; Torello, Cristiane O; Ramos, Aline L; Oliveira, Alaíde B; Rocha, Fabíola D; Arruda, Vanessa A; Accorci, Walter R

2008-05-01

319

COMPARATIVE MEDICINE LABORATORY ANIMAL FACILITIES  

E-print Network

. Additionally, mice should be tested for Helicobacter as outlined in SOP 2.D.6, "Animal Health Monitoring health concerns: i. Additional testing of the sentinels or quarantine animals may be required2.D.9 COMPARATIVE MEDICINE LABORATORY ANIMAL FACILITIES STANDARD OPERATING PROCEDURES for ANIMAL

Krovi, Venkat

320

Cytotoxicity and Cellular Internalization Studies of Biogenic Gold Nanotriangles in Animal Cell Lines  

Microsoft Academic Search

Biogenic gold nanotriangles have been used in this study to understand their cytotoxicity and biocompatibility in animal cells. These gold nanotriangles were synthesized using the leaf extract of the lemon grass (Cymbopogan flexuosus) plant. Cancerous as well as non-cancerous cells were used to study their dose dependent viability on exposure to the gold nanotriangles. Additionally, it has been shown that

Amit Singh; Ravi Shukla; Shabir Hassan; R. R. Bhonde; Murali Sastry

2011-01-01

321

BEHAVIORAL EFFECTS OF MODERATE LEAD EXPOSURE IN CHILDREN AND ANIMAL MODELS. PART 1: CLINICAL STUDIES  

EPA Science Inventory

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...

322

Animal cytomegaloviruses.  

PubMed Central

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. PMID:2170830

Staczek, J

1990-01-01

323

Animal Cell Mitosis Animation  

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.

2010-01-01

324

Humanized Mice, a New Model To Study the Influence of Drug Treatment on Neonatal Sepsis  

PubMed Central

Bacterial infection with group B Streptococcus (GBS) represents a prominent threat to neonates and fetuses in the Western world, causing severe organ damage and even death. To improve current therapeutic strategies and to investigate new approaches, an appropriate in vivo model to study the immune response of a human immune system is needed. Therefore, we introduced humanized mice as a new model for GBS-induced sepsis. Humanized mice feature deficiencies similar to those found in neonates, such as lower immunoglobulin levels and myeloid cell dysfunction. Due to the husbandry in specific-pathogen-free (SPF) facilities, the human immune cells in these mice also exhibit a naive phenotype which mimics the conditions in fetuses/neonates. Following infection, cytokine release and leukocyte trafficking from the bone marrow to the lymphoid organ (spleen) and into the peritoneum (site of infection) as well as bacterial spreading and clearance were traceable in the humanized mice. Furthermore, we investigated the effects of betamethasone and indomethacin treatment using this novel sepsis model. Although both drugs are commonly used in perinatal care, little is known about their effects on the neonatal immune system. Treatment of infected humanized mice not only induced the reduction of human leukocytes in the spleen but also increased the bacterial load in all analyzed organs, including the brain, which did not show infiltration of live GBS in untreated controls. These studies demonstrate the utility of the humanized mice as a new model to study an immature human immune response during bacterial infection and allow the investigation of side effects induced by various treatments. PMID:23439310

Ernst, Wolfgang; Zimara, Nicole; Hanses, Frank; Männel, Daniela N.; Seelbach-Göbel, Birgit

2013-01-01

325

Utilization of animal studies to determine the effects and human risks of environmental toxicants (drugs, chemicals, and physical agents).  

PubMed

Toxicology studies using animals and in vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Studies in pregnant animals are used to determine the risk of birth defects and other reproductive effects. There is no question that whole animal teratology studies are helpful in raising concerns about the reproductive effects of drugs and chemicals, but negative animal studies do not guarantee that these agents are free from reproductive effects. There are examples in which drug testing was negative in animals (rat and mouse) but was teratogenic in the human (thalidomide), and there are examples in which a drug was teratogenic in an animal model but not in the human (diflunisal). Testing in animals could be improved if animal dosing using the mg/kg basis were abandoned and drugs and chemicals were administered to achieve pharmacokinetically equivalent serum levels in the animal and the human. Because most human teratogens have been discovered by alert physicians or epidemiology studies, not animal studies, animal studies play a minor role in discovering teratogens. In vitro studies play an even less important role, although they are helpful in describing the cellular or tissue effects of the drugs or chemicals. One cannot determine the magnitude of human risks from these in vitro studies. Performing toxicology studies on adult animals is performed by pharmaceutical companies, chemical companies, the Food and Drug Administration, many laboratories at the National Institutes of Health, and scientific investigators in laboratories throughout the world. Although a vast amount of animal toxicology studies are performed on pregnant animals and numerous toxicology studies are performed on adult animals, there is a paucity of animal studies using newborn, infant, and juvenile animals. This deficiency is compounded by the fact that there are very few toxicology studies performed in children. That is why pregnant women and children are referred to as "therapeutic orphans." When animal studies are performed with newborn and developing animals, the results demonstrate that generalizations are less applicable and less predictable than the toxicology studies in pregnant animals. Although many studies reveal that the infant and the developing animal have difficulty in metabolizing drugs and are more vulnerable to the toxic effects of environmental chemicals, there are exceptions that indicate that infant and developing animals may be less vulnerable and more resilient to some drugs and chemicals. In other words, the generalization indicating that developing animals are always more sensitive to environmental toxicants is not valid. For animal toxicology studies to be useful, animal studies have to use modern concepts of pharmacokinetics and toxicokinetics, as well as method-of-action studies to determine whether animal data can be used for determining human risk. One example is the inability to determine carcinogenic risks in humans for some drugs and chemicals that produce tumors in rodents, because the oncogenesis is the result of peroxisome proliferation, a reaction that is of diminished importance in humans. Scientists can use animal studies to study the toxicokinetic and toxicodynamic aspects of environmental toxicants, but they have to be performed with the most modern techniques and interpreted with the highest level of scholarship and objectivity. Threshold exposures, maximum permissible exposures, and toxic effects can be estimated but have to be interpreted with caution when applying them to the human. Well-performed epidemiology studies are still the best method for determining the human risk and the effects of environmental toxicants. PMID:15060191

Brent, Robert L

2004-04-01

326

In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study  

PubMed Central

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. PMID:24743103

Maschauer, Simone; Ruckdeschel, Tina; Tripal, Philipp; Haubner, Roland; Einsiedel, Jürgen; Hübner, Harald; Gmeiner, Peter; Kuwert, Torsten; Prante, Olaf

2014-01-01

327

Experimental studies on the infectivity of non-culturable forms of Campylobacter spp. in chicks and mice.  

PubMed Central

The significance of non-culturable forms of Campylobacter spp., especially with regard to the epidemiology of this organism in poultry flocks, was explored. Two different experiments were conducted to produce non-culturable Campylobacter spp. and test their ability to colonize the animal gut. In the first experiment a mixture of 28 different strains of Campylobacter spp. from various sources was inoculated in both sterilized surface water and potassium phosphate buffer and stored at 4 degrees C. After Campylobacter spp. were no longer detectable by culture in the microcosms, the mixtures of non-culturable cells were used to challenge both chicks and mice. Recovery of non-culturable Campylobacter spp. from the animals was not successful at 4 weeks after administration. In the second experiment the survival of six individual strains of Campylobacter spp. in sterilized surface water at 4 degrees C was studied and the resulting non-culturable cells were used to challenge chicks. None of the campylobacter strains could be recovered from the chicks at 2 weeks after administration. We conclude that occurrence of non-culturable forms of Campylobacter spp. capable of colonizing chicks is not a common phenomenon and that non-culturable forms of Campylobacter spp. are likely to be insignificant for importantly to the epidemiology of the organism in Dutch broiler flocks. PMID:8972670

van de Giessen, A. W.; Heuvelman, C. J.; Abee, T.; Hazeleger, W. C.

1996-01-01

328

Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model  

PubMed Central

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. PMID:23914333

Cai, Wei-Xin; Zheng, Li-Wu; Weber, Franz E.; Li, Chun-Lei; Ma, Li; Ehrbar, Martin

2013-01-01

329

Animal Imaging  

Microsoft Academic Search

\\u000a This chapter discusses challenges and practical approaches to animal fMRI with respect to anesthetic regimens, conscious animal\\u000a studies, activation paradigms, optimal pulse sequence selection, and the rigor required for drug discovery applications. Examples\\u000a on the use of animal fMRI to support drug discovery are presented. The examples illustrate (1) technical development and qualification\\u000a of a quantitative assay for pain, (2)

Donald Williams; Alexandre Coimbra; Fuqiang Zhao

330

Large animal models for the study of ovarian follicular dynamics in women.  

PubMed

Initial studies of the ovaries were based on postmortem anatomic descriptions, followed by histologic and endocrine approaches. The introduction of high-resolution ultrasonography provided a long-awaited tool to image the reproductive tissues in situ in both animals and humans. Critical studies of the characteristics and control of ovarian follicular and luteal dynamics in nonhuman primates, rodents, and domestic farm animals have involved frequent (i.e., daily or multiple times a day) blood sampling and ultrasonography. Studies of this nature in women are difficult, and often unethical to conduct. Differences in antral folliculogenesis between humans and animals appear to be more in detail rather than in essence, and may reflect differences in intrinsic physiology or merely differences in our ability to detect changes in a given species. In women, the presence of endometrial shedding and symmetric luteal and follicular phases are different from that observed during the estrous cycles of domestic farm animals but despite these differences, general similarities in antral follicular dynamics exist. A continuous pattern of antral follicle development was originally proposed in domestic livestock species; however, the use of frequent serial ultrasonography and simultaneous endocrine profiling in these animal species has resulted in a broad understanding of follicular wave dynamics. Follicular waves have now been described in every species in which this approach has been used, including humans. The relatively large diameters of antral follicles in cows and mares, compared with monkeys, sheep, and rodents provide greater feasibility for characterizing antral follicular dynamics ultrasonographically. While the use of large animal models has increased our understanding of ovarian function and provides the hypothetical basis for studies in women, differences in vocabulary, culture, and research methodologies has hampered knowledge translation. These differences represent a systemic impediment to a broad understanding of ovarian function and limits progress and innovation in the development of safer and more efficacious treatments for infertility and contraception. PMID:22626769

Adams, G P; Singh, J; Baerwald, A R

2012-11-01

331

Prospects for new information relevant to radiation protection from studies of experimental animals  

SciTech Connect

The theory underlying radiation protection was developed from studies of people, laboratory animals, tissues, cells and macromolecules. Data on people were obtained from opportunistic studies of individuals previously exposed to radiation. Rarely has it been possible to conduct prospective studies of people exposed to known quantities of radiation, which sharply restricts the nature of questions that they can address. In contrast, studies using laboratory animals and simpler biological systems can be designed to address specific questions, using controlled exposure conditions. In-vitro research with macromolecules, cells and tissues leads to understanding normal and disease processes in isolated biological components. Studies of the intact animals provide opportunities to study in vivo interactive mechanisms observed in vitro and their role in development of radiation-induced diseases such as cancer. In the future, studies of intact animals should prove increasingly valuable in linking new knowledge at the subanimal level with the more fragmentary information obtained from direct observations on people. This will provide insight into important issues such as (a) effects of low-level radiation exposures, (b) mechanism of cancer induction at high versus low radiation doses, and (c) influence of factors such as nutrition and exposure to chemicals on radiation-induced cancer. This presentation describes strategies for conducting and integrating results of research using macromolecules, cells, tissues, laboratory animals and people to improve our understanding of radiation-induced cancer. It will also emphasize the problems encountered in studies at all levels of biological organization when the disease is observed in low excess incidence long after exposure to the toxicant.

McClellan, R.O.

1988-08-01

332

Study of the clomipramine-morphine interaction in the forced swimming test in mice  

Microsoft Academic Search

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective

A. Eschalier; J. Fialip; O. Varoquaux; M.-C. Makambila

1987-01-01

333

Mayo Clinic study finds nutritional supplement works against some pancreatic cancer cells in mice  

Cancer.gov

The dietary supplement gamma-linolenic acid can inhibit the growth of a subset of pancreatic cancer cells and selectively promote cancer cell death in mice, a Mayo Clinic study has found. The supplement, a fatty acid also known as GLA, worked particularly well when combined with the chemotherapy drug gemcitabine, the researchers say.

334

Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice  

Microsoft Academic Search

In this study, the ability of chitosan microparticles to enhance both the systemic and local immune responses against diphtheria toxoid (DT) after oral and nasal administration in mice was investigated.Firstly, DT was associated to chitosan microparticles to determine antigen loading and release. Then DT loaded chitosan microparticles, DT in phosphate buffered saline (PBS) and empty chitosan microparticles (as controls) were

Inez M. van der Lubben; Gideon Kersten; Marjan M. Fretz; Coen Beuvery; J. Coos Verhoef; Hans E. Junginger

2003-01-01

335

410 | VOL.9 NO.4 | APRIL2012 | nAture methods the study of social interactions in mice is used as a model for  

E-print Network

, depression, impulsive and personality disorders1,2. Mice that show dysfunctional choices can constitute,4 During social interactions, mice make multiple and fast behavioral changes and exhibit a rich behavioral by applying computer-vision methods that automati- cally track multiple animals9­11 (ants and fruit flies

Cai, Long

336

Preliminary Studies on the Antinociceptive Activity of Vaccinium ashei Berry in Experimental Animal Models  

PubMed Central

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. PMID:20170358

Ramirez, Maria Rosana; Guterres, Leandra; Dickel, Odila E.; de Castro, Micheli R.; Henriques, Amelia T.; de Souza, Márcia M.

2010-01-01

337

Preflight studies on tolerance of pocket mice to oxygen and heat. I - Physiological studies  

NASA Technical Reports Server (NTRS)

Tests were carried out on pocket mice to ascertain their tolerance to elevated oxygen pressures alone and to a combination of hyperoxia and heat in excess of that expected during the flight of the mice on Apollo XVII. The mice withstood oxygen partial pressures up to 12 psi at normal room temperature (24 C, 75 F) over a period of 7 days. A few mice previously exposed to increased PO2 died in the course of exposure to an oxygen pressure of 10 psi or 12 psi (517 mm or 620 mm Hg) for 13 d in ambient heat of 32 C (90 F). Supplemental vitamin E and physiological saline loading given prior to exposure had no apparent protective effect. The overall conclusion was that the pocket mice which were to go on Apollo XVII could readily survive the ambient atmosphere to which they would be exposed.

Leon, H. A.; Suri, K.; Mctigue, M.; Smith, J.; Cooper, W.; Miquel, J.; Ashley, W. W.; Behnke, A. R., Jr.; Saunders, J. F.

1975-01-01

338

Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration.  

PubMed

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8-9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy. PMID:16332275

Libby, Richard T; Anderson, Michael G; Pang, Iok-Hou; Robinson, Zachary H; Savinova, Olga V; Cosma, I Mihai; Snow, Amy; Wilson, Lawriston A; Smith, Richard S; Clark, Abbot F; John, Simon W M

2005-01-01

339

Experimental study on anti-tumor and anti-inflammatory effect of Thespesia populnea phytochemical extract in mice models.  

PubMed

In the present study, we have conducted a dose- and duration-dependent response of phytochemical extract of Thespesia populnea (Malvaceae) plant native of costal forest of India. Our earlier studies revealed the anti-oxidant and chemoprotective effect of this plant extract. In the present study, we have attempted to study the anti-tumor and anti-inflammatory response of T. populnea using experimental mouse models. Our studies revealed that administration of T. populnea methanol extract was shown to inhibit the solid tumor development in mice. T. populnea treatment significantly reduced tumor cell glutathione (GSH) levels as well as serum ?-glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in the tumor-bearing animals (p < 0.01). The total white blood cell count and hemoglobin levels were also significantly increased in extract-treated hosts (p < 0.05, p < 0.01). The use of T. populnea substantially reduced the acute inflammation (assessed as paw edema) induced by carrageenan and also reduced inflammation edema induced by formalin. These studies suggest that T. populnea extract could be used as a (natural) anti-inflammatory and anti-tumor agent. PMID:23098275

Mika, Denish; Guruvayoorappan, C

2013-02-01

340

Analysis of Grooming Behavior and Its Utility in Studying Animal Stress, Anxiety, and Depression  

E-print Network

Chapter 2 Analysis of Grooming Behavior and Its Utility in Studying Animal Stress, Anxiety of grooming activity and its microstructure may serve as a useful measure of stress and anxiety in both wild into the effects of stress, anxiety, and depression on this behavioral domain. The method involves quantification

Kalueff, Allan V.

341

Mechanisms of the clasp-knife reflex studied in an animal model  

Microsoft Academic Search

Summary The mechanisms of the clasp-knife reflex were studied in the soleus muscle of an animal model, the decerebrate cat with a dorsal hemisection of the lower thoracic cord. The reflex is shown to be autogenetic, and to depend on muscle length in keeping with previous suggestions. However, the magnitude of the inhibition increases with increasing initial force, and the

W. Z. Rymer; J. C. Houk; P. E. Crago

1979-01-01

342

Percutaneous dilatational versus conventional open tracheotomy in a growing animal: A study in goats  

Microsoft Academic Search

Percutaneous dilatational tracheotomy (PDT) is a new technique for the inroduction of a tracheal cannula. It has been performed successfully in adults; however, in children, the open conventional technique is preferred because of the technical limitations of PDT, with fear of tracheal stenosis and adverse effects on tracheal growth. The authors studied the applicability of PDT in a growing animal.

L. W. E van Heurn; A. E. J. M van den Bogaard; G Kootstra; P. R. G Brink

1996-01-01

343

Caffeine physical dependence: a review of human and laboratory animal studies  

Microsoft Academic Search

Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety

Roland R. Griffiths; Phillip P. Woodson

1988-01-01

344

Estrogen-regulated non-reproductive behaviors and breast cancer risk: Animal models and human studies  

Microsoft Academic Search

The possible role of personality patterns and psychosocial factors in breast cancer has been studied extensively, through both human and animal experiments. The data are conflicting, and the conclusions controversial. This review will serve two purposes. First, we present evidence that behavioral patterns most commonly linked to breast cancer risk are at least partly regulated by estrogens. This section will

Leena Hilakivi-Clarke

1997-01-01

345

Studies on the Use of Animals of Economic Importance in Schools  

ERIC Educational Resources Information Center

The purpose of keeping animals in schools and problems encountered in their maintenance are summarized. Two curriculum units, one on fruit flies and one on honey bees are described. Reasons for a widespread negative image of rural studies are discussed and positive outcomes of an environmental science course are presented. (Author/EB)

Blum, Abraham

1976-01-01

346

Increasing Physical Activity in Preschool: A Pilot Study to Evaluate Animal Trackers  

ERIC Educational Resources Information Center

Objective: This report describes a pilot study to evaluate Animal Trackers (AT), a preschool program designed to (1) increase structured physical activity (PA) during the preschool day; (2) increase practice of gross motor skills; (3) provide teachers with an easy-to-use PA program regardless of teacher experience; and (4) implement a teacher…

Williams, Christine L.; Carter, Betty Jean; Kibbe, Debra L.; Dennison, David

2009-01-01

347

Tools for studying animal behaviour: validation of dive profiles relayed via the Argos satellite system  

E-print Network

Tools for studying animal behaviour: validation of dive profiles relayed via the Argos satellite satellite system (http://www.argosinc.com). Behavioural data relayed remotely via the Argos satellite system of their time submerged, further limiting the time available for communication with satel- lites. The problem

Hays, Graeme

348

Use of animal studies for assessing intakes of inhaled actinide-bearing dusts  

Microsoft Academic Search

This paper reviews the methodology used in the execution and interpretation of animal studies (mostly conducted at NRPB) designed to provide guidance on limits of intake and the effectiveness of chest monitoring for persons exposed to various uranium, plutonium, americium, and thorium bearing dusts. The lung retention and transportability characteristics of the actinides in humans have been predicted by combining

G. N. Stradling; J. C. Moody

1995-01-01

349

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.

Kari E. Benson

2004-01-01

350

A high speed functional microCT detector for small animal studies  

Microsoft Academic Search

Dedicated microCT systems for noninvasive screening of small animals are now in routine use. However, speed of operation limits their use for functional studies. At RMD we are addressing this need by developing a digital X-ray detector that can simultaneously provide high speed, high sensitivity, and a large active imaging area. The system consists of a special high speed CCD

Vivek V. Nagarkar; Sameer V. Tipnis; Irina Shestakova; Valeriy Gaysinskiy; Bipin Singh; M. J. Paulus; Gerald Entine

2004-01-01

351

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

2012-01-01

352

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.

2008-01-01

353

Generating Animal and Tool Names: An fMRI Study of Effective Connectivity  

ERIC Educational Resources Information Center

The present fMRI study of semantic fluency for animal and tool names provides further evidence for category-specific brain activations, and reports task-related changes in effective connectivity among defined cerebral regions. Two partially segregated systems of functional integration were highlighted: the tool condition was associated with an…

Vitali, P.; Abutalebi, J.; Tettamanti, M.; Rowe, J.; Scifo, P.; Fazio, F.; Cappa, S.F.; Perani, D.

2005-01-01

354

Investigation of exposure to Extremely Low Frequency (ELF) magnetic and electric fields: Ongoing animal studies  

SciTech Connect

There is now convincing evidence from a large number of laboratories, that exposure to extremely low frequency (ELF) magnetic and electric fields produces biological responses in animals. Many of the observed effects appear to be directly or indirectly associated with the neural or neuroendocrine systems. Such effects include increased neuronal excitability, chemical and hormonal changes in the nervous system, altered behavioral responses, some of which are related to sensing the presence of the field, and changes in endogenous biological rhythms. Additional indices of general physiological status appear relatively unaffected by exposure, although effects have occasionally been described in bone growth and fracture repair, reproduction and development, and immune system function. A major current emphasis in laboratory research is to determine whether or not the reported epidemiological studies that suggest an association between EMF exposure and risk of cancer are supported in studies using animal models. Three major challenges exist for ongoing research: (1) knowledge about the mechanisms underlying observed bioeffects is incomplete, (2) researchers do not as yet understand what physical aspects of exposure produce biological responses, and (3) health consequences resulting from ELF exposure are unknown. Although no animal studies clearly demonstrate deleterious effects of ELF fields, several are suggestive of potential health impacts. From the perspective of laboratory animal studies, this paper will discuss biological responses to ELF magnetic and/or electric field exposures.

Anderson, L.E.

1994-03-01

355

INHALATION STUDIES OF MT. ST. HELENS VOLCANIC ASH IN ANIMALS. 1. INTRODUCTION AND EXPOSURE SYSTEM  

EPA Science Inventory

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 determine the acute and chronic health effects of a short-term exposure. This paper describes the inhalat...

356

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.

2004-01-01

357

Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies.  

PubMed Central

Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies are discussed. In the area of experimental design, issues that must be considered include randomization of animals, sample size considerations, dose selection and allocation of animals to experimental groups, and control of potentially confounding factors. In the analysis of tumor incidence data, survival differences among groups should be taken into account. It is important to try to distinguish between tumors that contribute to the death of the animal and "incidental" tumors discovered at autopsy in an animal dying of an unrelated cause. Life table analyses (appropriate for lethal tumors) and incidental tumor tests (appropriate for nonfatal tumors) are described, and the utilization of these procedures by the National Toxicology Program is discussed. Despite the fact that past interpretations of carcinogenicity data have tended to focus on pairwise comparisons in general and high-dose effects in particular, the importance of trend tests should not be overlooked, since these procedures are more sensitive than pairwise comparisons to the detection of carcinogenic effects. No rigid statistical "decision rule" should be employed in the interpretation of carcinogenicity data. Although the statistical significance of an observed tumor increase is perhaps the single most important piece of evidence used in the evaluation process, a number of biological factors must also be taken into account. The use of historical control data, the false-positive issue and the interpretation of negative trends are also discussed. PMID:6525993

Haseman, J K

1984-01-01

358

Understanding Animal Research  

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)

2009-01-01

359

Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes  

PubMed Central

Background We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice. PMID:24758191

2014-01-01

360

In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals.  

PubMed

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

1993-08-01

361

Development of implant loading device for animal study about various loading protocol: a pilot study  

PubMed Central

PURPOSE The aims of this pilot study were to introduce implant loading devices designed for animal study and to evaluate the validity of the load transmission ability of the loading devices. MATERIALS AND METHODS Implant loading devices were specially designed and fabricated with two implant abutments and cast metal bars, and orthodontic expansion screw. In six Beagles, all premolars were extracted and two implants were placed in each side of the mandibles. The loading device was inserted two weeks after the implant placement. According to the loading protocol, the load was applied to the implants with different time and method,simulating early, progressive, and delayed loading. The implants were clinically evaluated and the loading devices were removed and replaced to the master cast, followed by stress-strain analysis. Descriptive statistics of remained strain (µ?) was evaluated after repeating three cycles of the loading device activation. Statistic analysis was performed using nonparametric, independent t-test with 5% significance level and Friedman's test was also used for verification. RESULTS The loading devices were in good action. However, four implants in three Beagles showed loss of osseointegration. In stress-strain analysis, loading devices showed similar amount of increase in the remained strain after applying 1-unit load for three times. CONCLUSION Specialized design of the implant loading device was introduced. The loading device applied similar amount of loads near the implant after each 1-unit loading. However, the direction of the loads was not parallel to the long axis of the implants as predicted before the study. PMID:23236575

Yoon, Joon-Ho; Park, Young-Bum; Cho, Yuna; Kim, Chang-Sung; Choi, Seong-Ho; Moon, Hong-Seok; Lee, Keun-Woo

2012-01-01

362

Productively Infected Murine Kaposi's Sarcoma-Like Tumors Define New Animal Models for Studying and Targeting KSHV Oncogenesis and Replication  

PubMed Central

Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat) enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells. PMID:24489895

Ashlock, Brittany M.; Ma, Qi; Issac, Biju; Mesri, Enrique A.

2014-01-01

363

Prolonged diet induced obesity has minimal effects towards brain pathology in mouse model of cerebral amyloid angiopathy: implications for studying obesity-brain interactions in mice.  

PubMed

Cerebral amyloid angiopathy (CAA) occurs in nearly every individual with Alzheimer's disease (AD) and Down's syndrome, and is the second largest cause of intracerebral hemorrhage. Mouse models of CAA have demonstrated evidence for increased gliosis contributing to CAA pathology. Nearly two thirds of Americans are overweight or obese, with little known about the effects of obesity on the brain, although increasingly the vasculature appears to be a principle target of obesity effects on the brain. In the current study we describe for the first time whether diet induced obesity (DIO) modulates glial reactivity, amyloid levels, and inflammatory signaling in a mouse model of CAA. In these studies we identify surprisingly that DIO does not significantly increase A? levels, astrocyte (GFAP) or microglial (IBA-1) gliosis in the CAA mice. However, within the hippocampal gyri a localized increase in reactive microglia were increased in the CA1 and stratum oriens relative to CAA mice on a control diet. DIO was observed to selectively increase IL-6 in CAA mice, with IL-1? and TNF-? not increased in CAA mice in response to DIO. Taken together, these data show that prolonged DIO has only modest effects towards A? in a mouse model of CAA, but appears to elevate some localized microglial reactivity within the hippocampal gyri and selective markers of inflammatory signaling. These data are consistent with the majority of the existing literature in other models of A? pathology, which surprisingly show a mixed profile of DIO effects towards pathological processes in mouse models of neurodegenerative disease. The importance for considering the potential impact of ceiling effects in pathology within mouse models of A? pathogenesis, and the current experimental limitations for DIO in mice to fully replicate metabolic dysfunction present in human obesity, are discussed. This article is part of a Special Issue entitled: Animal Models of Disease. PMID:23313575

Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J; Freeman, Linnea R; Pepping, Jennifer K; Beckett, Tina L; Murphy, M Paul; Keller, Jeffrey N

2013-09-01

364

Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice  

PubMed Central

Introduction The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. Methods Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. Results OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. Conclusions Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis. PMID:21992149

2011-01-01

365

Ameliorative Effects of Acanthopanax trifoliatus on Cognitive and Emotional Deficits in Olfactory Bulbectomized Mice: An Animal Model of Depression and Cognitive Deficits  

PubMed Central

Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable and a tonic. This study investigated effects of the aqueous extract of its leaves (ATL) on cognitive and emotional deficits using an olfactory bulbectomized mouse (OBX) model. OBX mice were treated daily with ATL (250 and 500?mg/kg, p.o.) 3 days after OBX. Antidementia drug tacrine (2.5?mg/kg/day) and antidepressant drug imipramine (10?mg/kg/day) were given i.p. as reference drugs. OBX significantly impaired cognitive behavior in a novel object recognition test and a modified Y-maze test and induced depression-like behavior in a tail suspension test. ATL and tacrine treatment attenuated OBX-induced cognitive deficits, whereas ATL and imipramine improved OBX-induced depression-like behavior. Neurochemical studies conducted after completing behavioral experiments demonstrated that OBX downregulated the expression levels of cholinergic marker genes encoding choline acetyltransferase and muscarinic M1 receptor in a manner reversed by ATL and tacrine. Moreover, ATL and tacrine administration inhibited the ex vivo activity of acetylcholinesterase in the brain. These findings suggest that ATL is beneficial for the treatment of cognitive and emotional deficits related to dementia with depressive symptoms and that the antidementia effect of ATL is mediated by normalizing the function of central cholinergic systems. PMID:23573147

Sithisarn, Pongtip; Rojsanga, Piyanuch; Jarikasem, Siripen; Tanaka, Ken; Matsumoto, Kinzo

2013-01-01

366

Acetaminophen-induced Acute Liver Injury in HCV Transgenic Mice  

PubMed Central

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 hrs after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. PMID:23200774

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

2012-01-01

367

Ultrastructural and morphometrical study of preimplantation endometrium in superovulated mice treated with progesterone or Sildenafil  

PubMed Central

Background: Endometrial development has an important role in blastocyst adhesion and implantation. During IVF cycles, endometrial development is enhanced by progesterone. Objective: The aim of this study was to compare ultrastructural and morphometrical characteristics of mice uterine endometrium in natural cycle with those in superovulated cycles received progesterone or Sildenafil. Materials and Methods: In This study, 60 female bulb/c mice were divided into 4 groups: a control and 3 experimental; gonadotropin, gonadotropin+ Sildenafil and gonadotropin+ progesterone. In experimental groups the mice superovulated mated. In the gonadotropin+ progesterone and gonadotropin+ Viagra groups, the mice respectively received 1mg progesterone and 3 mg Sildenafil citrate. Their uterine specimens were prepared for morphometrical and ultrastructural study. Height of the epithelial cells was measured, using motic software. Statistical analysis was performed using ANOVA. Results: Microscopy revealed that in control group the cells had numerous apical microvilli and the height of the cells was 20.52±2.43 µm. In gonadotropin+ progesterone group, the granules were found in basal and apical portions and cellular height were 17.91±2.78 µm which were significantly shorter than in the control and gonadotropin groups (p<0.001). In this group, the apical membrane also contained pinopodes. In gonadotropin +Sildenafil group, the granules were found in both apical and basal portions and the height of the cells were 17.60±2.49 µm which were significantly shorter than in the control and gonadotropin groups (p<0.001). In this group, pinopodes appeared slightly extensive than the other groups. Conclusion: It is concluded that superovulatory drugs in mice stimulate endometrial maturation but injection of Sildenafil is nearly more positive. This article extracted from Ph.D. thesis. (Bahman Rashedee) PMID:24639701

Roshangar, Leila; Soleimani-Rad, Jafar; Rashedee, Bahman; Mazochian, Hossein; Nikzad, Behzad; Soleimani Rad, Sara

2013-01-01

368

Oxytocin in the Treatment of Dystocia in Mice  

PubMed Central

Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. PMID:22330862

Narver, Heather L

2012-01-01

369

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

PubMed

The diagnosis of Post-Traumatic Stress Disorder (PTSD) is conditional on directly experiencing or witnessing a significantly threatening event and the presence of a certain minimal number of symptoms from each of four symptom clusters (re-experiencing, avoidance, negative cognition and mood, and hyperarousal) at least one month after the event (DSM 5) (American Psychiatric Association 2013). Only a proportion of the population exposed develops symptoms fulfilling the criteria. The individual heterogeneity in responses of stress-exposed animals suggested that adapting clearly defined and reliably reproducible "diagnostic", i.e. behavioral, criteria for animal responses would augment the clinical validity of the analysis of study data. We designed cut-off (inclusion/exclusion) behavioral criteria (CBC) which classify study subjects as being severely, minimally or partially affected by the stress paradigm, to be applied retrospectively in the analysis of behavioral data. Behavioral response classification enables the researcher to correlate (retrospectively) specific anatomic, bio-molecular and physiological parameters with the degree and pattern of the individual behavioral response, and also introduces "prevalence rates" as a valid study-parameter. The cumulative results of our studies indicate that, by classifying the data from individual subjects according to their response patterns, the animal study can more readily be translated into clinical "follow-up" studies and back again. This article will discuss the concept of the model and its background, and present a selection of studies employing and examining the model, alongside the underlying translational rationale of each. PMID:25225303

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

2014-01-01

370

SiliPET: design of an ultra high resolution small animal PET scanner based on stacks of semiconductor detectors  

Microsoft Academic Search

We have studied with Monte Carlo simulations, using the EGSnrc code, a new scanner for small-animal positron emission tomography (PET) based on stacks of double sided semiconductor detectors. In small animal PET imaging (mice) Compton scattering within the animal itself is not an issue and therefore registration of the energy information is not necessary. Low Z materials can therefore be

Natalia Auricchio; Nicola Cesca; G. Di Domenico; E. Moretti; S. Sabba; M. Gambaccini; G. Zavattini; R. Andritschke; G. Kanbach; F. Schopper

2005-01-01

371

The influence of oral L-arginine on fracture healing: an animal study  

Microsoft Academic Search

BACKGROUND: The known biological activities of nitric oxide suggest a role in bone healing. We hypothesized that L-arginine, a source of nitric oxide, expedites the healing process of stabilized diaphyseal defects. TYPE OF STUDY: Prospective blinded animal study. METHODS: Using a guinea-pig model, a 7 mm diaphyseal and periosteal defect was produced in the right femur and splinted intramedullary with a

Richard K. Kdolsky; Wolfgang Mohr; Helga Savidis-Dacho; Rudolf Beer; Stefan Puig; Roland Reihsner; Stefan Tangl; Karl Donath

2005-01-01

372

Opportunities for the replacement of animals in the study of nausea and vomiting  

PubMed Central

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. PMID:19371333

Holmes, AM; Rudd, JA; Tattersall, FD; Aziz, Q; Andrews, PLR

2009-01-01

373

Selection of an appropriate animal model for study of bone loss in weightlessness  

NASA Technical Reports Server (NTRS)

Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

Wolinsky, I.

1986-01-01

374

The effect of low and high plasma levels of insulin-like growth factor-1 (IGF-1) on the morphology of major organs: studies of Laron dwarf and bovine growth hormone transgenic (bGHTg) mice.  

PubMed

It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals. To study the effects of insulin-like growth factor-1 (IGF-1) plasma level on the morphology of major organs, we analyzed lung, heart, liver, kidney, bone marrow, and spleen isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice (with low circulating plasma levels of IGF-1) and 6-month-old bovine growth hormone transgenic (bGHTg) mice (with high circulating plasma levels of IGF-1). The ages of the two mutant strains employed in our studies were selected based on their overall ~50% survival (Laron dwarf mice live up to ~4 years and bGHTg mice up to ~1 year). Morphological analysis of the organs of long-living 2-year-old Laron dwarf mice revealed a lower biological age for their organs compared with normal littermates, with more brown adipose tissue (BAT) surrounding the main body organs, lower levels of steatosis in liver, and a lower incidence of leukocyte infiltration in different organs. By contrast, the organs of 6-month-old, short-living bGHTg mice displayed several abnormalities in liver and kidney and a reduced content of BAT around vital organs. PMID:23613169

Piotrowska, Katarzyna; Borkowska, Sylwia J; Wiszniewska, Barbara; Laszczy?ska, Maria; S?uczanowska-G?abowska, Sylwia; Havens, Aaron M; Kopchick, John J; Bartke, Andrzej; Taichman, Russel S; Kucia, Magda; Ratajczak, Mariusz Z

2013-10-01

375

Anti-scorpion venom activity of Andrographis paniculata: A combined and comparative study with anti-scorpion serum in mice  

PubMed Central

Objectives: The objective of this study is to evaluate the anti-scorpion venom (ASV) property of Andrographis paniculata in comparison with anti-redscorpion venom serum and this study aimed to determine its combined effect with anti-redscorpion venom serum. Materials and Methods: Ethanolic extract of the plant AP was obtained using soxhlet apparatus. Swiss albino mice weighing 20-30g were used. Lyophilized venom sample of Mesobuthus tamulus and Lyophilized monovalent enzyme refined immunoglobulin anti-scorpion venom serum (ASV) was used. Using lethal dose of scorpion venom (25.12?g/g), the venom neutralizing ability of plant extract (1 g/kg) and ASV individually as well as in combination was studied using in vivo and in vitro methods. Mean survival time, protection fold and percentage survival of animals over the period of 24 h were the parameters used. Statistical Analysis: Results were analyzed using Student's t-test. Results: Ethanolic extract of AP (1 g/kg) showed some protective effect against scorpion venom. ASV was found more effective than plant extract. But, when plant extract and ASV were used in combination, potency of ASV was found to be increased both in vivo and in vitro. Conclusions: Present study demonstrates that, both plant extract and ASV have their own scorpion venom neutralising ability in vivo and in vitro, but their combination is most effective in venom neutralizing ability. PMID:24501444

Kale, Ranjana S.; Bahekar, Satish E.; Nagpure, Shailesh R.; Salwe, Kartik J.

2013-01-01

376

Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease  

NASA Astrophysics Data System (ADS)

Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine ?-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the A? precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

2013-05-01

377

A Systematic Proteomic Study of Irradiated DNA Repair Deficient Nbn-Mice  

PubMed Central

Background The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals. Methodology/Principal Findings We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst ?8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs. Conclusions/Significance In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress. PMID:19412544

Melchers, Anna; Stöckl, Lars; Radszewski, Janina; Anders, Marco; Krenzlin, Harald; Kalischke, Candy; Scholz, Regina; Jordan, Andreas; Nebrich, Grit; Klose, Joachim; Sperling, Karl

2009-01-01

378

A comparative study into alterations of coenzyme Q redox status in ageing pigs, mice, and worms.  

PubMed

Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized endogenously in almost all species and function as an obligatory cofactor of the respiratory chain. There is evidence that CoQ status is altered by age in several species. Here we determined level and redox-state of CoQ in different age groups of pigs, mice and Caenorhabditis elegans. Since these species are very different with respect to lifespan, reproduction and physiology, our approach could provide some general tendencies of CoQ status in ageing organisms. We found that CoQ level decreases with age in pigs and mice, whereas CoQ content increases in older worms. As observed in all three species, ubiquinone, the oxidized form of CoQ, increases with age. Additionally, we were able to show that supplementation of ubiquinol-10, the reduced form of human CoQ10 , slightly increases lifespan of post-reproductive worms. In conclusion, the percentage of the oxidized form of CoQ increases with age indicating higher oxidative stress or rather a decreased anti-oxidative capacity of aged animals. PMID:24578032

Onur, Simone; Niklowitz, Petra; Fischer, Alexandra; Metges, Cornelia C; Grune, Tilman; Menke, Thomas; Rimbach, Gerald; Döring, Frank

2014-01-01

379

Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies.  

PubMed

Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research. PMID:22776123

Duan, Qiwen; Liu, Yanfeng; Booth, Carmen J; Rockwell, Sara

2012-03-01

380

The effect of continuous infusion of human parathyroid hormone on bone architecture in female mice  

E-print Network

This research sought to create an animal model of secondary hyperparathyroidism through continuous infusion of parathyroid hormone (PTH) in adult female mice, and to subsequently study the catabolic effects of PTH. Osmotic ...

Eisenberg, Rahel E. (Rahel Esther)

2009-01-01

381

Mitochondrial dna evolution in mice  

Microsoft Academic Search

This study extends knowledge of mitochondrial DNA (mtDNA) diversity in mice to include 208 animals belonging to eight species in the subgenus Mus. Highly purified mtDNA from each has been subjected to high-resolution re- striction mapping with respect to the known sequence of one mouse mtDNA. Variation attributed to base substitutions was encountered at about 200 of the 300 cleavage

STEPHEN D. FERRIS; RICHARD D. SAGE; ELLEN M. PRAGER; U Ritte; A C Wilson

1983-01-01

382

Technique for measuring carbon monoxide uptake in mice  

SciTech Connect

A new method has been developed for measuring carbon monoxide (CO) uptake in mice. Each animal was placed in a syringe and allowed to rebreathe a mixture of CO and helium (He) for 60 s. CO uptake was detemined from a comparison of CO and He concentrations before and after rebreathing. Weight specific CO uptake increased with body weight in CBA mice weighing between 20 to 35 gr. In larger mice, size dependence was less marked, although a slight fall in CO uptake was observed in older animals. Anaesthesia reduced ventilatory rate and CO uptake to a variable extent. The method is reproducible, non-invasive and does not require anaesthesia; consequently, it can be used to study serial changes in lung function. It is sensitive enough to detect lung damage in CBA mice following 16 Gy total body irradiation. Values of diffusing capacity obtained for mice using this method are consistent with published values.

Depledge, M.H.; Collis, C.H.; Chir, B.; Barrett, A.

1981-04-01

383

Animal Models of Hemophilia  

PubMed Central

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

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

2013-01-01

384

A feasibility study of PETiPIX: an ultra high resolution small animal PET scanner  

NASA Astrophysics Data System (ADS)

PETiPIX is an ultra high spatial resolution positron emission tomography (PET) scanner designed for imaging mice brains. Four Timepix pixellated silicon detector modules are placed in an edge-on configuration to form a scanner with a field of view (FoV) 15 mm in diameter. Each detector module consists of 256 × 256 pixels with dimensions of 55 × 55 × 300 ?m3. Monte Carlo simulations using GEANT4 Application for Tomographic Emission (GATE) were performed to evaluate the feasibility of the PETiPIX design, including estimation of system sensitivity, angular dependence, spatial resolution (point source, hot and cold phantom studies) and evaluation of potential detector shield designs. Initial experimental work also established that scattered photons and recoil electrons could be detected using a single edge-on Timepix detector with a positron source. Simulation results estimate a spatial resolution of 0.26 mm full width at half maximum (FWHM) at the centre of FoV and 0.29 mm FWHM overall spatial resolution with sensitivity of 0.01%, and indicate that a 1.5 mm thick tungsten shield parallel to the detectors will absorb the majority of non-coplanar annihilation photons, significantly reducing the rates of randoms. Results from the simulated phantom studies demonstrate that PETiPIX is a promising design for studies demanding high resolution images of mice brains.

Li, K.; Safavi-Naeini, M.; Franklin, D. R.; Petasecca, M.; Guatelli, S.; Rosenfeld, A. B.; Hutton, B. F.; Lerch, M. L. F.

2013-12-01

385

Optical spectroscopic studies of animal skin used in modeling of human cutaneous tissue  

NASA Astrophysics Data System (ADS)

Optical spectroscopy and in particular laser-induced autofluorescence spectroscopy (LIAFS) and diffuse reflectance spectroscopy (DRS), provide excellent possibilities for real-time, noninvasive diagnosis of different skin tissue pathologies. However, the introduction of optical spectroscopy in routine medical practice demands a statistically important data collection, independent from the laser sources and detectors used. The scientists collect databases either from patients, in vivo, or they study different animal models to obtain objective information for the optical properties of various types of normal and diseased tissue. In the present work, the optical properties (fluorescence and reflectance) of two animal skin models are investigated. The aim of using animal models in optical spectroscopy investigations is to examine the statistics of the light induced effects firstly on animals, before any extrapolation effort to humans. A nitrogen laser (?=337.1 nm) was used as an excitation source for the autofluorescence measurements, while a tungsten-halogen lamp was used for the reflectance measurements. Samples of chicken and pig skin were measured in vitro and were compared with results obtained from measurements of normal human skin in vivo. The specific features of the measured reflectance and fluorescence spectra are discussed, while the limits of data extrapolation for each skin type are also depicted.

Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Borisova, E.; Avramov, L.; Sianoudis, J. A.

2007-03-01

386

Data base on animal mortality  

SciTech Connect

A data base on animal mortality has been compiled. The literature on LD/sub 50/ and the dose-response function for radiation-induced lethality, reflect several inconsistencies - primarily due to dose assignments and to analytical methods and/or mathematical models used. Thus, in order to make the individual experiments which were included in the data base as consistent as possible, an estimate of the uniform dose received by the bone marrow in each treatment group was made so that the interspecies differences are minimized. The LD/sub 50/ was recalculated using a single estimation procedure for all studies for which sufficient experimental data are available. For small animals such as mice, the dose to the hematopoietic system is approximately equal to the treatment dose, but for large animals the marrow dose may be about half of the treatment dose.

Jones, T.D.

1987-01-01

387

Small animal radiotherapy research platforms  

NASA Astrophysics Data System (ADS)

Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research.

Verhaegen, Frank; Granton, Patrick; Tryggestad, Erik

2011-06-01

388

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.

2002-06-01

389

Behavioral thermoregulatory responses of single- and group-housed mice.  

PubMed

The ambient temperature (Ta) to house and study laboratory rodents is critical for nearly all biomedical studies. The ideal Ta for housing rodents and other animals should be based on their thermoregulatory requirements. However, fundamental information on the behavioral thermoregulatory responses of single- and group-housed rodents is meager. To address this issue, thermoregulatory behavior was assessed in individual and groups of CD-1 mice housed in a temperature gradient. Mice were housed in groups of five or individually while selected Ta and motor activity were monitored. Single- and group-housed mice displayed a circadian oscillation of selected Ta and motor activity with relatively warm T(a)s of approximately 29 degrees C selected during the light phase; during the dark phase selected Ta was reduced by 4 degrees C, whereas motor activity increased. Selected Ta of aged (11 months old) mice housed individually was approximately 1.0 degrees C warmer than the group-housed mice. Thermal preference of younger mice (2 months old) was similar for single- and group-housed animals. The operative Ta of mice housed in standard facilities was estimated by measuring the cooling rate of "phantom" mice modeled from aluminum cylinders. The results show that the typical housing conditions for single- and group-housed mice are cooler than their Ta for ideal thermal comfort. PMID:9855474

Gordon, C J; Becker, P; Ali, J S

1998-11-15

390

Cholinesterase inhibition and alterations of hepatic metabolism by oral acute and repeated chlorpyrifos administration to mice  

Microsoft Academic Search

Chlorpyrifos (CPF) is a broad spectrum organophosphorus insecticide bioactivated in vivo to chlorpyrifos-oxon (CPFO), a very potent anticholinesterase. A great majority of available animal studies on CPF and CPFO toxicity are performed in rats. The use of mice in developmental neurobehavioural studies and the availability of transgenic mice warrant a better characterization of CPF-induced toxicity in this species. CD1 mice

Maria Francesca Cometa; Franca Maria Buratti; Stefano Fortuna; Paola Lorenzini; Maria Teresa Volpe; Laura Parisi; Emanuela Testai; Annarita Meneguz

2007-01-01

391

Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed  

PubMed Central

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of ‘high-quality’ SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments. PMID:20551243

Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

2010-01-01

392

The history and enduring contributions of planarians to the study of animal regeneration.  

PubMed

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. PMID:23799578

Elliott, Sarah A; Sánchez Alvarado, Alejandro

2013-01-01

393

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

SciTech Connect

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

Kubota, K.; Som, P.; Brill, A.B.; Sacker, D.F.; Meinken, G.E.; Srivastava, S.C.; Atkins, H.L. (Brookhaven National Lab., Upton, NY (USA))

1989-11-01

394

Studies on the pathogenesis of actinomycotic mycetoma in animals injected with fractions isolated from Nocardia brasiliensis.  

PubMed Central

In the present study the participation was evaluated of isolated fractions of Nocardia brasiliensis in the genesis of the inflammatory response observed in actinomycotic mycetoma. Subcutaneous injection in mice of a suspension containing a polysaccharide fraction F1 obtained by treating cell walls with sodium hydroxide induced an inflammatory response at the inoculation site which was characterized by a large influx of polymorphonuclear (PMN) and mononuclear (MN) leucocytes between the 2nd and 4th days. On the 8th day, a typical granulomatous reaction was observed involving large numbers of epithelioid cells. Intravenous injection of the lipid extract adsorbed to charcoal particles into mice induced an inflammatory reaction around the particles embolized in the pulmonary microcirculation which was similar to that described above. The kinetics of the inflammatory cell migration was studied by total and differential counts of leukocytes that migrated to the peritoneal cavity of rats inoculated intraperitoneally with the F1 and lipid fractions. Both fractions initially induced intense PMN migration, which was later reduced, with a simultaneous increase in mononuclear cells. The present results demonstrate that a polysaccharide fraction (F1) and the lipid fraction reproduce the fundamental lesion of actinomycotic mycetoma. Images Fig. 1 Fig. 2 PMID:3814496

Ekizlerian, S. M.; Brandão Filho, S. L.; Tincani, I.; Alves, L. M.; Silva, C. L.

1987-01-01

395

An Animal Model for the Study of Small-Bowel Tumors1  

Microsoft Academic Search

SUMMARY An animal model for the study of small-bowel tumors has been investigated. Tumors were induced in male Holtzman rats by X-irradiation of only the hypoxic, temporarily exteriorized ileum and jejunum. Following an exposure of 2000 R, 56% of the rats developed adenocarcinoma some where in the irradiated segment. Macroscopic métastases were not observed outside the small intestine: however, métastases

Kenneth L. Coop; J. Graham Sharp; James W. Osborne; George R. Zimmerman

396

A study of cystic echinococcosis in slaughter animals in three selected areas of northern Turkana, Kenya  

Microsoft Academic Search

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

2002-01-01

397

New animal model to study epigenetic mechanisms mediating altered gravity effects upon cell growth and morphogenesis  

NASA Astrophysics Data System (ADS)

The gravitational field and its variations act as a major environmental factor that can impact morphogenesis developing through epigenetic molecular mechanisms. The mechanisms can be thoroughly investigated by using adequate animal models that reveal changes in the morpho-genesis of a growing organ as a function of gravitational effects. Two cooperative US/Russian experiments on Foton-M2 (2005) and Foton-M3 (2007) were the first to demonstrate differences in the shape of regenerating tails of space-flown and ground control newts. The space-flown and aquarium (simulated microgravity) animals developed lancet-shaped tails whereas 1 g con-trols (kept in space-type habitats) showed hook-like regenerates. These visual observations were supported by computer-aided processing of the images and statistical analysis of the results. Morphological examinations and cell proliferation measurements using BrdU demon-strated dorsal-ventral asymmetry as well as enhanced epithelial growth on the dorsal area of regenerating tails in 1 g newts. These findings were reproduced in laboratory tests on newts kept at 1 g and in large water tanks at cut g. The 1 g animals showed statistically significant deviations of the lancet-like tail shape typically seen in aquarium animals. Such modifications were found as early as regeneration stages III-IV and proved irreversible. The authors believe that the above phenomenon detected in newts used in many space experiments can serve as an adequate model for studying molecular mechanisms underlying gravitational effects upon animal morphogenesis.

Grigoryan, Eleonora N.; Dvorochkin, Natasha; Radugina, Elena A.; Poplinskaya, Valentina; Novikova, Julia; Almeida, Eduardo

398

Evaluation of traditional plant treatments for diabetes: Studies in streptozotocin diabetic mice  

Microsoft Academic Search

Summary  Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice.\\u000a The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Artemisia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes,

Sara K. Swanston-Flatt; Caroline Day; Clifford J. Bailey; Peter R. Flatt

1989-01-01

399

The Functional Paradox of CD43 in Leukocyte Recruitment: A Study Using CD43-deficient Mice  

Microsoft Academic Search

Summary Although there is considerable evidence implicating a role for CD43 (leukosialin) in leukocyte cell-cell interactions, its precise function remains uncertain. Using CD43-deficient mice (CD43 2 \\/ 2 ) and intravital microscopy to directly visualize leukocyte interactions in vivo, we in- vestigated the role of CD43 in leukocyte-endothelial cell interactions within the cremasteric microcirculation under flow conditions. Our studies demonstrated

Richard C. Woodman; Brent Johnston; Michael J. Hickey; Diane Teoh; Paul Reinhardt; Betty Y. Poon; Paul Kubes

400

Review of certain low-level ionizing radiation studies in mice and guinea pigs  

Microsoft Academic Search

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

Charles C. Congdon

1987-01-01

401

Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report  

SciTech Connect

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.

Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

1988-08-01

402

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

PubMed Central

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

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

2015-01-01

403

Puberty as a critical risk period for eating disorders: a review of human and animal studies.  

PubMed

This article is part of a Special Issue "Puberty and Adolescence". Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. PMID:23998681

Klump, Kelly L

2013-07-01

404

A Longitudinal Low Dose ?CT Analysis of Bone Healing in Mice: A Pilot Study  

PubMed Central

Low dose microcomputed tomography (?CT) is a recently matured technique that enables the study of longitudinal bone healing and the testing of experimental treatments for bone repair. This imaging technique has been used for studying craniofacial repair in mice but not in an orthopedic context. This is mainly due to the size of the defects (approximately 1.0?mm) in long bone, which heal rapidly and may thus negatively impact the assessment of the effectiveness of experimental treatments. We developed a longitudinal low dose ?CT scan analysis method combined with a new image segmentation and extraction software using Hounsfield unit (HU) scores to quantitatively monitor bone healing in small femoral cortical defects in live mice. We were able to reproducibly quantify bone healing longitudinally over time with three observers. We used high speed intramedullary reaming to prolong healing in order to circumvent the rapid healing typical of small defects. Bone healing prolongation combined with ?CT imaging to study small bone defects in live mice thus shows potential as a promising tool for future preclinical research on bone healing. PMID:25431676

Di, Lu-Zhao; Leblanc, Élisabeth; Alinejad, Yasaman; Beaudoin, Jean-François; Lecomte, Roger; Berthod, François; Faucheux, Nathalie; Balg, Frédéric

2014-01-01

405

Comparative studies on animal models for Opisthorchis viverrini infection: host interaction through susceptibility and pathology.  

PubMed

Syrian hamsters and gerbils are animal models for Opisthorchis viverrini infection. In both models, the parasites develop into adults with different pathologies of the hepatobiliary system. However, no comparative pathological studies have yet been completed. We therefore investigated host interaction through the susceptibility and pathological changes of Syrian hamsters and gerbils infected with 50 O. viverrini metacercariae for 30, 60, and 90 days post-infection. Animals were sacrificed at each time point for comparative study. Susceptibility and infectivity were investigated through worm burden. Parasite morphology and reproductive organs were stained with carmine and observed under light microscopy. Reproductive organs and eggs per worm were counted to confirm worm maturity. Bile acid components of both animal groups were analyzed by thin-layer chromatography. The results showed that infection in gerbils was of greater severity than in Syrian hamsters by observation of bile obstruction, enlargement of the gallbladder and common bile duct, and generation of fibrosis and cirrhosis. The worm burden of infected gerbils was lower than that observed in Syrian hamsters. Infectivity in both Syrian hamsters and gerbils was 100% with infection by 50 metacercariae; whereas with 10 metacercariae, the infectivity in gerbils was zero to very low, but still 100% in Syrian hamsters. The largest body size of worms, and the largest ovary and testes areas, was correlated with eggs per gram of feces and eggs per worm. The bile acid components cholic acid and chenodeoxycholic acid were undetectable in gerbils. The present study suggests that