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1

First Results of Small Animal Imaging Spect Detector for Cardiovascular Disease Studies on Mice  

NASA Astrophysics Data System (ADS)

We have developed a compact, open, Dual Head pinhole SPECT system for high resolution molecular imaging with radionuclides of mice, dedicated mainly to preclinical study of stem cells capability to recover myocardial infarction. The gamma detector is made of pinhole tungsten collimators, pixellated scintillators, matrix of multi-anode PMTs and individual channel readout. Measurements have been performed on phantoms and live mice devoted initially to test and calibrate the system and to optimize protocols. The implemented system and the first results will be presented, demonstrating the effectiveness of our dedicated SPECT detector for small animal imaging.

Magliozzi, M. L.; Ballerini, M.; Cisbani, E.; Colilli, S.; Cusanno, F.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Santavenere, F.; Torrioli, S.; Veneroni, P.; Majewsky, S.; Mok, S. P. G.; Tsui, B. M. W.; Wang, Y.; Marano, G.; Musumeci, M.; Palazzesi, S.; Ciccariello, G.; de Vincentis, G.; Accorsi, R.

2008-06-01

2

Sleep apnea in mice: a useful animal model for study of SIDS?  

Microsoft Academic Search

Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest

Akira Nakamura; Tomoyuki Kuwaki

2003-01-01

3

Sleep apnea in mice: a useful animal model for study of SIDS?  

Microsoft Academic Search

Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest

Akira Nakamura; Tomoyuki Kuwaki

2004-01-01

4

Establishment of an Animal Model Using Recombinant NOD.B10.D2 Mice To Study Initial Adhesion of Oral Streptococci  

PubMed Central

An oral biofilm is a community of surface-attached microorganisms that coats the oral cavity, including the teeth, and provides a protective reservoir for oral microbial pathogens, which are the primary cause of persistent and chronic infectious diseases in patients with dry mouth or Sjögren's syndrome (SS). The purpose of this study was to establish an animal model for studying the initial adhesion of oral streptococci that cause biofilm formation in patients with dry mouth and SS in an attempt to decrease the influence of cariogenic organisms and their substrates. In nonobese diabetogenic (NOD) mice that spontaneously develop insulin-dependent diabetes mellitus (IDDM) and SS, we replaced major histocompatibility complex (MHC) class II (Ag7 Eg7) and class I Db with MHC class II (Ad Ed) and class I Dd from nondiabetic B10.D2 mice to produce an animal model that inhibited IDDM without affecting SS. The adhesion of oral streptococci, including Streptococcus mutans, onto tooth surfaces was then investigated and quantified in homologous recombinant N5 (NOD.B10.D2) and N9 (NOD.B10.D2) mice. We found that a higher number of oral streptococci adhered to the tooth surfaces of N5 (NOD.B10.D2) and N9 (NOD.B10.D2) mice than to those of the control C57BL/6 and B10.D2 mice. On the basis of our observation, we concluded that these mouse models might be useful as animal models of dry mouth and SS for in vivo biological studies of oral biofilm formation on the tooth surfaces.

Salam, Mohammad Abdus; Matsumoto, Naoko; Matin, Khairul; Tsuha, Yuzo; Nakao, Ryoma; Hanada, Nobuhiro; Senpuku, Hidenobu

2004-01-01

5

Are NCAM deficient mice an animal model for schizophrenia?  

PubMed Central

Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we studied social interaction and attention of NCAM null mutant (NCAM?/?) mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM?/? mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three—compartment—box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM?/? mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.

Albrecht, Anne; Stork, Oliver

2012-01-01

6

Pharmacokinetic Studies of Norfloxacin in Laboratory Animals  

Microsoft Academic Search

Pharmacokinetic studies were conducted with norfloxacin administered by the oral and subcutaneous routes to mice and rats, and by the oral route to rhesus monkeys. The compound was moderately well absorbed following oral dosing in these animal species. Serum levels in monkeys ranged from 1.0 to 2.35 ?g\\/ml after an oral drug dose of 25 mg\\/kg of animal body weight

E. C. Gilfillan; B. A. Pelak; J. A. Bland; P. F. Malatesta; H. H. Gadebusch

1984-01-01

7

Studies on the optimal immunization schedule of experimental animals. IV. The optimal age and sex of mice, and the influence of booster injections.  

PubMed

To establish the optimal condition for preparing mouse antiserum specific to a drug, the optimal age and sex of mice for the immune response were studied by measuring the mouse serum levels of total immunoglobulin G (IgG) and specific antibody to viomycin, as well as the changes in weight of mice immunized with a viomycin immunogen. It was observed that age was a more important factor than sex, and strongly affected productions of both total and specific IgGs of mice. The mice aged 8 weeks yielded the highest levels of both total IgG and the specific antibody. In the study on the influence of booster schedule, the number of boosters given had a larger influence on the immune response than the interval between priming and boosters. The greater the number of booster shots given, the less was the production of total and specific antibodies. The decrease in the weight of mice after immunization was also studied in more detail; it was found that it only occurred in the first week after priming but not after a booster injection. The mice aged eight weeks showed the largest weight loss. PMID:2337959

Hu, J G; Yokoyama, T; Kitagawa, T

1990-02-01

8

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

9

Companion animal adoption study.  

PubMed

To better understand the outcomes of companion animal adoptions, Bardsley & Neidhart Inc. conducted a series of 3 surveys over a 1-year period with dog and cat owners who had adopted their pet through either a (a) Luv-A-Pet location, (b) Adopt-a-thon, or (c) traditional shelter. This article suggests opportunities to improve owners' perceptions of their pets and the adoption process through (a) providing more information before adoption about pet health and behaviors, (b) providing counseling to potential adopters to place pets appropriately, and (c) educating adopters to promote companion animal health and retention. Results demonstrate that the pet's relationship to the family unit, such as where the pet sleeps and how much time is spent with the pet, is related to the amount of veterinary care the companion animal receives, and to long-term retention. Satisfaction and retention are attributed to the pet's personality, compatibility, and behavior, rather than demographic differences among adopters or between adoption settings. The age of the companion animal at adoption, the intended recipient, and presence of children in the home also play a role. Health problems were an issue initially for half of all adopted pets, but most were resolved within 12 months. Roughly one fourth of adopters who no longer have their companion animal said their pet died. Characteristics of pets that died support the contention that spaying and neutering profoundly affects a companion animal's life span. Although retention is similar for dogs and cats, mortality is higher among cats in the first year after adoption. PMID:12578739

Neidhart, Laura; Boyd, Renee

2002-01-01

10

Big mice die young but large animals live longer.  

PubMed

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

2013-04-01

11

Animal models to study environmental epigenetics.  

PubMed

Epigenetics provides a means of understanding how environmental factors might alter heritable changes in gene expression without changing DNA sequence, and hence the origin, of some diseases that are not explained by conventional genetic mechanisms. Various animal models have been described, most notably the agouti viable yellow (A(vy)) and axin 1 fused (Axin1(Fu)) mice, which lend themselves particularly well to studying this link between epigenetics and development abnormalities, because particular changes in DNA methylation patterns can be linked to a broad spectrum of heritable pathologies in the mice. In addition, there are specific examples, both in mice and other animal species, where nonmutagenic, environmental insults to either parent, such as those caused by consumption of endocrine-disrupting chemicals, can cause unexpected transgenerational phenotypic changes in offspring. Animals derived by somatic cell nuclear transfer also frequently exhibit pathologies that can be linked to inappropriate nuclear reprogramming during early embryo development and provide another means to study a link between epigenetics and disease. This review will consider how all of these animal models might help elucidate the epigenetic basis for a wide range of phenotypes. PMID:19828779

Rosenfeld, Cheryl S

2009-10-14

12

Helicobacter spp. in Wild Mice (Peromyscus leucopus) Found in Laboratory Animal Facilities  

PubMed Central

Wild rodents are a potential source for pathogen introduction into laboratory animal research facilities. A study was designed to assess wild mice found at our institution by infectious disease surveillance. Wild white-footed mice (Peromyscus leucopus) were captured with live capture traps placed in areas in which wild mice had been reported in several animal facilities. Captured animals were euthanized by inhalation of CO2, blood was collected by cardiocentesis (n = 10), and necropsy was performed (n = 8). Serum samples were negative for antibodies to mouse parvovirus (types 1 and 2), mouse minute virus, Sendai virus, pneumonia virus of mice, mouse hepatitis virus, Theiler murine encephalomyelitis virus, reovirus, rotavirus, lymphocytic choriomeningitis virus, mouse adenovirus, ectromelia virus, K virus, cilia-associated respiratory bacillus, and Mycoplasma pulmonis. Of the 8 animals that were necropsied, pelt and cecal examinations were negative for ectoparasites and pinworms, respectively. Histopathologic examination of brain, heart, lungs, liver, kidney, spleen, stomach, and small intestine revealed bacteria morphologically compatible with Helicobacter spp. in the cecal and colonic glands and occasionally in the gastric lumen and pits. Mesenteric lymph nodes and feces from 8 of the animals were submitted for PCR analysis for the detection of mouse parvovirus, mouse minute virus, mouse hepatitis virus, and Helicobacter spp.; 7 of the samples were PCR-positive for Helicobacter spp. At this time, wild mice found in our animal facilities do not appear to be a significant source of common laboratory mouse viral pathogens. However, they are a potential source of Helicobacter infections.

Dyson, Melissa C; Eaton, Kathryn A; Chang, Cherie

2009-01-01

13

In Vivo Quantitation of Glucose Metabolism in Mice Using Small-Animal PET and a Microfluidic Device  

Microsoft Academic Search

The challenge of sampling blood from small animals has ham- peredtherealizationofquantitativesmall-animalPET.Difficulties associatedwiththeconventionalblood-samplingprocedureneed to be overcome to facilitate the full use of this technique in mice. Methods: We developed an automated blood-sampling device on an integrated microfluidic platform to withdraw small blood samples from mice. We demonstrate the feasibility of performing quantitative small-animal PET studies using 18F-FDG and input functions derived

Hsiao-Ming Wu; Guodong Sui; Cheng-Chung Lee; Mayumi L. Prins; Waldemar Ladno; Hong-Dun Lin; Amy S. Yu; Michael E. Phelps; Sung-Cheng Huang

14

Value of juvenile animal studies.  

PubMed

The Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute has undertaken a project to address the impact of juvenile animal studies on pediatric drug development. A workshop, sponsored and organized by the Health and Environmental Sciences Institute Developmental and Reproductive Toxicity Technical Committee, was held on May 5-6, 2010, in Washington, DC, to discuss the outcome of a global survey and the value of juvenile animal studies in the development of drugs intended for use in pediatric patients. During this workshop, summary data from the 2009-2010 survey were presented, and breakout sessions were used to discuss specific case studies to try to assess the impact of juvenile animal studies performed to support specific pediatric drug development. The objectives of the Workshop on The Value of Juvenile Animal Studies were to (1) provide a forum for scientists representing industry, academia, and regulatory agencies to discuss the impact of juvenile animal studies on pediatric drug development, (2) evaluate summary data from the survey to understand how the juvenile study data are being used and their impact in labeling and risk assessment, (3) discuss selected case studies from the survey to highlight key findings, and (4) identify the areas of improvement for the designs of juvenile animal studies. The take home message that resonated from the workshop discussions was that well-designed juvenile animal studies have demonstrated value in support of certain pediatric drug development programs. However, it was also clear that a juvenile animal study is not always warranted. PMID:22623020

Leconte, Isabelle; Bailey, Graham; Davis-Bruno, Karen; Hew, Kok Wah; Kim, James; Silva Lima, Beatriz; Liminga, Ulla; Moffit, Jeffrey; De Schaepdrijver, Luc; Schmitt, Georg; Tassinari, Melissa; Thompson, Kary; Hurtt, Mark

2011-08-01

15

Animal studies of addictive behavior.  

PubMed

It is increasingly recognized that studying drug taking in laboratory animals does not equate to studying genuine addiction, characterized by loss of control over drug use. This has inspired recent work aimed at capturing genuine addiction-like behavior in animals. In this work, we summarize empirical evidence for the occurrence of several DSM-IV-like symptoms of addiction in animals after extended drug use. These symptoms include escalation of drug use, neurocognitive deficits, resistance to extinction, increased motivation for drugs, preference for drugs over nondrug rewards, and resistance to punishment. The fact that addiction-like behavior can occur and be studied in animals gives us the exciting opportunity to investigate the neural and genetic background of drug addiction, which we hope will ultimately lead to the development of more effective treatments for this devastating disorder. PMID:23249442

Vanderschuren, Louk J M J; Ahmed, Serge H

2013-04-01

16

SCID Mice Transplanted With Human Cells as Small Animal Models in AIDS Research  

Microsoft Academic Search

The progress in AIDS research has been hampered by the lack of a small and practical animal model susceptible to HIV infection,\\u000a suitable for a rapid testing of antiviral compounds and vaccines. Over the past 20 years, different attempts have been made\\u000a to develop various models for AIDS in mice. An ensemble of studies carried out in several laboratories during

Caterina Lapenta; Stefano M. Santini; Massimo Spada; Filippo Belardelli

17

Insulin resistance induced by zymosan as a new animal model in mice.  

PubMed

Insulin resistance (IR) is known as a main problem in diabetic disorders. Some animal models for research in IR have been mentioned. Each model shows merit with some disadvantages. Thus, a new animal model for IR is required. The present study used zymosan, a mixture of cell-wall particles from the yeast named Saccharomyces cerevisiae, to establish a new model of IR in mice. Also, we compared the difference of this model with fructose-rich chow-induced model and found some merits of this model. Moreover, we identified that this model induced by zymosan is reversible and IR can be reversed gradually after termination of treatment. Taken together, we suggest zymosan as a useful agent to induce IR through inflammatory pathway in mice. PMID:23860764

Wang, L-Y; Ku, P-M; Chen, S-H; Chung, H-H; Yu, Y-M; Cheng, J-T

2013-07-16

18

Expression of Interleukin4 in the Epidermis of Transgenic Mice Results in a Pruritic Inflammatory Skin Disease: An Experimental Animal Model to Study Atopic Dermatitis  

Microsoft Academic Search

Atopic dermatitis, a common, chronic, inflammatory skin disease that occurs with increasing prevalence, is characterized by hyperactivated cytokines of helper T cell subset 2 and is frequently associated with staphylococcal infection. An experimental animal model of atopic dermatitis induced by transgenically introduced cytokine is not available. We generated a transgenic mouse line expressing epidermal interleukin-4, a critical cytokine of helper

Lawrence S. Chan; Neha Robinson; Luting Xu

2001-01-01

19

Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice  

Microsoft Academic Search

The aim of the present study was to verify the effects of pre- or post-training paradoxical sleep (PS) deprivation in mice tested in the passive and the plus-maze discriminative avoidance tasks. Three-month-old Swiss male mice were placed in narrow platforms in a water tank for 72h to prevent the occurrence of PS. Control animals were kept in the same room,

R. H. Silva; A. B. Chehin; S. R. Kameda; A. L. Takatsu-Coleman; V. C. Ab??lio; S. Tufik; R. Frussa-Filho

2004-01-01

20

Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-up.  

PubMed

Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC(0-t)) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/f(u)) (L/h) and log species body weight (W) (kg) [CL (or CL/f(u)) = 3.29 (34.0) W(0.723 (0.789))] and log V(ss) (or V(ss)/f(u)) (L) and log W (kg) [V(ss) (or V(ss)/f(u)) = 0.340 (3.52) W(0.882 (0.948))]. Interspecies scale-up of plasma concentration-time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration-time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. PMID:19226634

Kang, Hee E; Jung, Hye Y; Cho, Yu K; Kim, So H; Sohn, Se I; Baek, Seung R; Lee, Myung G

2009-11-01

21

Noggin heterozygous mice: an animal model for congenital conductive hearing loss in humans.  

PubMed

Conductive hearing loss occurs when sound waves are not relayed efficiently to the inner ear. Mutations of the NOGGIN (NOG) gene in humans are associated with several autosomal dominant disorders such as proximal symphalangism and multiple synostoses. These syndromes are characterized by skeletal defects and synostoses, which include conductive hearing loss. Noggin is an antagonist of bone morphogenetic proteins (BMPs), and balanced levels of BMPs and Noggin are required for proper skeletal formation. Depending on the genetic background, some of the Nog(+/-) mice display mild hearing loss, that is, conductive in nature. Since Noggin is a single exon gene, this data strongly suggest that the autosomal dominant disorders associated with NOG mutations are due to haploinsufficiency of NOGGIN. The conductive hearing loss in Nog(+/-) mice is caused by an ectopic bone bridge located between the stapes and the posterior wall of the tympanum, which affects the normal mobility of the ossicle. Our analyses suggest that the ectopic bone formation is caused by a failure of the stapes and styloid process to separate completely during development. This failure of bone separation in the Nog(+/-) mice reveals another consequence of chondrocyte hyperplasia due to unopposed Bmp activities in these mutants such as Bmp4 and Bmp14 (Gdf5). More importantly, these results establish Nog(+/-) mice as the first animal model for the study of conductive rather than neurosensory hearing loss that has direct relevance to human genetic disorders. PMID:18096605

Hwang, Chan-Ho; Wu, Doris K

2007-12-20

22

Update on animal models of diabetic retinopathy: from molecular approaches to mice and higher mammals  

PubMed Central

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the major causes of blindness worldwide. The pathogenesis of DR has been investigated using several animal models of diabetes. These models have been generated by pharmacological induction, feeding a galactose diet, and spontaneously by selective inbreeding or genetic modification. Among the available animal models, rodents have been studied most extensively owing to their short generation time and the inherited hyperglycemia and/or obesity that affect certain strains. In particular, mice have proven useful for studying DR and evaluating novel therapies because of their amenability to genetic manipulation. Mouse models suitable for replicating the early, non-proliferative stages of the retinopathy have been characterized, but no animal model has yet been found to demonstrate all of the vascular and neural complications that are associated with the advanced, proliferative stages of DR that occur in humans. In this review, we summarize commonly used animal models of DR, and briefly outline the in vivo imaging techniques used for characterization of DR in these models. Through highlighting the ocular pathological findings, clinical implications, advantages and disadvantages of these models, we provide essential information for planning experimental studies of DR that will lead to new strategies for its prevention and treatment.

Robinson, Remya; Barathi, Veluchamy A.; Chaurasia, Shyam S.; Wong, Tien Y.; Kern, Timothy S.

2012-01-01

23

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

24

The Injustice of Excluding Laboratory Rats, Mice, and Birds from the Animal Welfare Act  

Microsoft Academic Search

A major shortcoming of the Animal Welfare Act is its exclusion of the species most-used in experimentation-rats, mice, and birds. Considerations of justice dictate that extension of the law to these three species is the morally right thing to do. A brief history of how these species came to be excluded from the laws protecting laboratory animals is also provided,

F. Barbara Orlans

2000-01-01

25

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

26

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

PubMed Central

The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of our investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, we investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. We propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

Chubb, C

1987-01-01

27

Creation of "Humanized" Mice to Study Human Immunity  

PubMed Central

“Humanized” mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strains such as NOD-scid IL2r? null mice that lack the IL-2 receptor common gamma chain. These stocks of mice lack adaptive immune function, display multiple defects in innate immunity, and support heightened levels of human hematolymphoid engraftment. Humanized mice can support studies in many areas of immunology, including autoimmunity, transplantation, infectious diseases, and cancer. These models are particularly valuable in experimentation where there is no appropriate small animal model of the human disease, as in the case of certain viral infections. This unit details the creation of humanized mice by engraftment of immunodeficient mice with hematopoietic stem cells or peripheral blood mononuclear cells, provides methods for evaluating engraftment, and discusses considerations for choosing the appropriate model system to meet specific goals.

Pearson, Todd; Greiner, Dale L.; Shultz, Leonard D.

2010-01-01

28

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

29

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

SciTech Connect

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 we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

Roszer, Tamas [Research Group of Apoptosis and Genomics, Hungarian Academy of Sciences, 4012 Debrecen, PO Box 6. (Hungary); Pintye, Eva [Department of Radiotherapy, Medical and Health Science Center, Debrecen University (Hungary); Benko', Ilona [Department of Pharmacology and Pharmacotherapy, Medical and Health Science Center, Debrecen University (Hungary)

2008-12-08

30

Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice.  

PubMed

Stereotyped behaviors (e.g., body rocking) occur at high rates in individuals with mental retardation (e.g., Down syndrome). To determine if spontaneous stereotypy occurs in a murine model of Down syndrome, the home cage behavior of Ts65Dn and control mice was monitored during the dark cycle. Motor activity was further assessed in novel automated test chambers, with acoustic startle and rotor rod paradigms providing additional environmental challenges. Spontaneous stereotypy (repetitive jumping and cage top twirling) was observed in the home cage in approximately half of the Ts65Dn mice, compared with approximately 10% of diploid controls. Repetitive jumping was observed exclusively in the Ts65Dn mice. In the open field, although no differences were found between Ts65Dn and control mice, stereotypic Ts65Dn mice exhibited significantly less locomotor activity and rearing relative to control and nonstereotypic Ts65Dn mice. Ts65Dn mice attained significantly lower rotor rod speeds but did not differ from controls in the amplitude of the acoustic startle response. These environmental challenges did not increase stereotypy over home cage rates but induced stereotypy in two additional animals. The Ts65Dn model may aid in identifying genes associated with the development and expression of stereotypy. PMID:11720125

Turner, C A; Presti, M F; Newman, H A; Bugenhagen, P; Crnic, L; Lewis, M H

2001-07-01

31

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 ...

Unsworth, Mrs.

2005-03-31

32

Animal Models Commonly Used to Study Quorum-Sensing Inhibitors  

Microsoft Academic Search

\\u000a Multiple animal models exist for the study of biofilm infections and\\u000a their inhibitors in vivo. The infection models described in this chapter range\\u000a from the simple nematode-killing and amoeba-plate-killing assays, to models\\u000a with more relevance to human disease like the pulmonary and cellulitis\\u000a infection models in mice, the graft prosthesis, and the central venous\\u000a catheter infection models in rats, and

Naomi Balaban; Michael Givskov; Thomas Bovbjerg Rasmussen; Andrea Giacometti; Oscar Cirioni

33

Ammonia disinfection of animal feeds --laboratory study.  

PubMed

Animal feeds may be contaminated, accidentally or maliciously, with a number of zoonotic bacteria. Animal infections with these bacterial agents, whether or not they cause animal disease, may lead to human illnesses. Anhydrous ammonia was introduced on farms in developed countries as a high-nitrogen soil amendment, but later found use in enhancing crude protein in low-quality roughage fed to ruminants and in neutralizing mycotoxins in fungus-infested feed grains. Although ammonia has been known to be effective against bacteria in other contexts (e.g., manure, community sewage sludge, seeds for sprouting, and boneless lean beef trimmings), it appears that the antibacterial effect of ammoniating animal feeds had not been tested. In the present study, samples of roughage (wheat straw, corn silage) and concentrates (corn grain, cottonseed) produced as animal feed were contaminated with dried-on zoonotic bacteria (Salmonella Newport in all; Campylobacte jejuni, E. coli O157:H7, Listeria monocytogenes, Yersinia enterocolitica in corn grain only). Disinfection with anhydrous ammonia gas was conducted for 24 h at room temperature ( 25 degrees C). The treatment was least effective in silage because the silage alone showed strong antibacterial activity, which may have been slightly reduced by ammoniation. In the other three feeds, depending on the initial level of contamination, ammonia destruction of >or= 5 log10 cfu/g (99.999%) of the selected contaminant was usually observed. PMID:18155794

Tajkarimi, Mehrdad; Riemann, Hans P; Hajmeer, Maha N; Gomez, Edward L; Razavilar, Vadood; Cliver, Dean O

2007-11-21

34

A multichannel, wireless telemetric microsystem for small animal studies  

Microsoft Academic Search

Conventional means of collecting biophysiological parameters in small animals often involve cumbersome direct wiring and\\/or restraint of the animal. At present, there is no system for very small animals that can provide multichannel monitoring of biopotentials without restraining the animal or small enough in size or light enough in weight for studies with smaller animals. For larger animals, such as

Chung-Chiun Liu; Edward O'Connor; Kingman P. Strohl

2006-01-01

35

STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE  

PubMed Central

1. Immunologic function, growth, and longevity of neonatally thymectomized mice was restored by intraperitoneal administration of 100 to 400 million syngeneic, hemiallogeneic, or ailogeneic thymus cells from newborn or adult donors. Assays of the graft versus host capabilities of spleen cells from the animals restored with allogeneic cells showed that their immunologically competent cells are of donor histocompatibility characteristics. Such animals accepted skin grafts from mice of the cell donor strain, but rejected skin from a third strain. 2. Similar results were obtained when the neonatally thymectomized animals were treated with 10 to 100 million syngeneic, hemiallogeneic, or allogeneic cells from adult spleen. 3. In one strain combination, C3H recipients and A donors, injected thymus or spleen cells apparently attacked host tissues, since the animals died very early of wasting disease. When this combination was reversed, A strain recipients treated with C3H cells were reconstituted immunologically and physiologically. 4. Syngeneic or allogeneic adult spleen, grafted in the newborn period, reconstituted neonatally thymectomized mice, but all experiments involving grafting of newborn spleen failed. Immunogenetic analysis of the host spleen cells from two allogeneic spleen-grafted animals previously thymectomized showed that the reconstitution was entirely of donor histocompatibility characteristics. 5. Postthymectomy wasting disease was reversed by administration of 200 million adult syngeneic spleen or thymus cells. Immunologic recovery was confirmed by graft versus host assays of the spleens of the recovered animals and by application of allogeneic skin grafts. Some of the animals have been under observation for 42 weeks and appear to be normal. 6. The wasting syndrome in neonatally thymectomized mice was also reversed by injection of 200 million hemiallogeneic or allogeneic spleen cells. 7. Thymus grafts did not reverse wasting disease, whether the donors were adult or newborn, of the same strain or a different one. 8. Spleen, lymph node, and Peyer's patches from representative animals of the reconstituted groups were examined and compared with the tissues of untreated neonatally thymectomized mice and intact animals of the same strain. Tissues of normal cellularity and follicular organization were found in some of the reconstituted animals and also in mice with reversed wasting disease. Extreme deficit of the lymphoid tissues was rare in either group.

Yunis, Edmond J.; Hilgard, Henry R.; Martinez, Carlos; Good, Robert A.

1965-01-01

36

Serial Sacrifice Study on Benzidine in Mice.  

National Technical Information Service (NTIS)

The animals used consisted of 1,728 F1 (C57BL/6JfC3Hf/Nctr females X BALB/cStCrlfC3Hf/Nctr males) and 1,728 monohybrid (F1 females X F1 males) mice. The animals were dosed with water containing 0, 30, 60, 120, 200, and 400 ppm benezidine dihydrochloride a...

G. Schieferstein

1982-01-01

37

Intrauterine effects of ultrasound: animal studies.  

PubMed

During the past several decades, the use of ultrasound technology in the clinical setting has greatly increased. Because nearly every pregnant woman receives at least one sonographic procedure today, there has been developing concern about the safety of such procedures. Since ultrasound exposure can result in hyperthermia and other physiological effects, the determination of a threshold or no-effect exposure has become a high-priority goal. Animal research has been important to the study of the effects of various exposures at all stages of pregnancy, since the clinical use of ultrasonography can occur during the preimplantation, organogenic, and fetal stages. Animal experiments using various mammalian species have been able to determine no-effect exposure levels for embryonic loss, congenital malformations and neurobehavioral effects. The preponderance of evidence from these studies indicates that, in the absence of a thermal effect, ultrasonography represents no measurable risk when used at recommended intensity levels. PMID:10331527

Jensh, R P; Brent, R L

1999-04-01

38

Animal models in translational studies of PTSD.  

PubMed

Understanding the neurobiological mechanisms of post-traumatic stress disorder (PTSD) is of vital importance for developing biomarkers and more effective pharmacotherapy for this disorder. The design of bidirectional translational studies addressing all facets of PTSD is needed. Animal models of PTSD are needed not only to capture the complexity of PTSD behavioral characteristics, but also to address experimentally the influence of variety of factors which might determine an individual's vulnerability or resilience to trauma, e.g., genetic predisposition, early-life experience and social support. The current review covers recent translational approaches to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers and novel therapeutics. PMID:23845512

Daskalakis, Nikolaos P; Yehuda, Rachel; Diamond, David M

2013-07-08

39

Demonstration of Nondeclarative Sequence Learning in Mice: Development of an Animal Analog of the Human Serial Reaction Time Task  

ERIC Educational Resources Information Center

|In this paper, we demonstrate nondeclarative sequence learning in mice using an animal analog of the human serial reaction time task (SRT) that uses a within-group comparison of behavior in response to a repeating sequence versus a random sequence. Ten female B6CBA mice performed eleven 96-trial sessions containing 24 repetitions of a 4-trial…

Christie, Michael A.; Hersch, Steven M.

2004-01-01

40

STUDIES ON MEGACOLON IN PIEBALD MICE  

Microsoft Academic Search

The incidence of megacolon has been studied in an inbred strain of mice (NZY) and in the descendants of NZY mice outcrossed to two other inbred strains (NZC, NZB) and to a fertile pituitary dwarf.The results of this study indicate that megacolon is an inheritable disease associated with \\

Marianne Bielschowsky; GC Schofield

1962-01-01

41

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.

Bellavite, Paolo; Ortolani, Riccardo; Conforti, Anita

2006-01-01

42

Histopathological and Ultrastructural Studies of Liver Tissue from TCDD-Exposed Beach Mice (Peromyscus polionotus).  

National Technical Information Service (NTIS)

Quantitative ultrastructural studies were conducted on liver tissue from beach mice, Peromyscus polionotus, exposed to the toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in field and laboratory environments. Hepatic tissue from 52 animals was examined f...

L. G. Cockerham A. L. Young C. E. Thalken

1980-01-01

43

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.

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

2011-01-01

44

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

45

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

46

Carcinogenesis Studies of Tetrahydrofuran Vapors in Rats and Mice  

Microsoft Academic Search

Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for carcinogenesis studies by the National Toxicology Program (NTP) because of its potential for widespread occupational exposure in humans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344\\/N rats and B6C3F1mice were exposed to 0, 200, 600, or 1800 ppm

R. S. Chhabra; R. A. Herbert; J. H. Roycroft; B. Chou; R. A. Miller; R. A. Renne

1998-01-01

47

Animation  

Microsoft Academic Search

\\u000a Right from its inception, a main strength of Flash has been its animation capabilities. Despite the arrival of ActionScript\\u000a programming shifting the focus somewhat, animation (or tweening in Flash authoring terms) is still considered a core feature of Flash. As yet, we have no timeline functionality for animating\\u000a 3D objects aside from some limited 2.5 effects (the “postcards in space”

Rob Bateman; Richard Olsson

48

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

49

Blunted Sensitivity to Sucrose in Autoimmune MRL-lpr Mice: A Curve-Shift Study  

Microsoft Academic Search

Lupus-prone MRL-lpr mice show an autoimmunity-associated behavioral syndrome that has many features similar to the effects of chronic stress. The present study evaluated whether autoimmune MRL-lpr mice show reduced responsiveness to sucrose, as observed in normal animals exposed to chronic mild stress. Sixteen-week old MRL-lpr mice and their age-matched congenic MRL +\\/+ controls were given 0%, 0.5%, 1%, 2%, 4%,

BORIS ŠAKI?; JUDAH A. DENBURG; SUSAN D. DENBURG; HENRY SZECHTMAN

1996-01-01

50

Study of Dengue Virus Infection in SCID Mice Engrafted with Human K562 Cells  

Microsoft Academic Search

Here we report that severe combined immunodeficient (SCID) mice engrafted with human K562 cells (K562-SCID mice) can be used as an animal model to study dengue virus (DEN) infection. After intratumor injection into K562 cell masses of PL046, a Taiwanese DEN-2 human isolate, the K562-SCID mice showed neurological signs of paralysis and died at approximately 2 weeks postinfection. In addition

YI-LING LIN; CHING-LEN LIAO; LI-KUANG CHEN; CHIA-TSUI YEH; CHIU-I LIU; SHIOU-HWA MA; YU-YING HUANG; YUE-LING HUANG; CHUAN-LIANG KAO

51

Mice Do Not Habituate to Metabolism Cage Housing-A Three Week Study of Male BALB/c Mice  

PubMed Central

The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.

Kalliokoski, Otto; Jacobsen, Kirsten R.; Darusman, Huda S.; Henriksen, Trine; Weimann, Allan; Poulsen, Henrik E.; Hau, Jann; Abelson, Klas S. P.

2013-01-01

52

Immunopharmacological Study of Inflammation in Mice.  

National Technical Information Service (NTIS)

Inflammation, due to the pharmacological mediators, sodium urate crystals, or to the allergic response, was studied in mice using the plethysmographic technique for measurement of paw swelling. With this technique it was possible to quantitate the respons...

E. M. Uyeki

1972-01-01

53

Inconsistent effects of photoperiod manipulations in tests for affective-like changes in mice: implications for the selection of appropriate model animals.  

PubMed

Deficiencies in appropriate animal models are a significant factor hindering the research of affective disorders. Significant data suggest that systems related to circadian rhythms are strongly linked to affective changes, but study with animal models in this context had unclear and inconsistent results. Circadian physiology is significantly different in diurnal and nocturnal animals and a recent project showed that in diurnal rodents, short photoperiods induce depression and anxiety-like phenotypes. This study was designed to evaluate the possibility that using a similar methodology would also result in behavioral changes in nocturnal mice. Mice from two strains were maintained in either short photoperiod, neutral photoperiod or long photoperiod for 3 weeks and tested for depression or anxiety-related behaviors, as done earlier with the diurnal rodents. Tests included activity levels, sweet solution preference, elevated plus-maze, resident-intruder aggression, and forced swim test. Tests were conducted either during the light phase or during the dark phase of the mice. In contrast to the clear phenotype in diurnal rodents, the effects of photoperiod manipulations in nocturnal mice were inconsistent. These results suggest that diurnal rodents may be advantageous compared with nocturnal species for studies exploring the relationship between circadian rhythms and affective disorders. PMID:21169813

Flaisher-Grinberg, Shlomit; Gampetro, Darcie R; Kronfeld-Schor, Noga; Einat, Haim

2011-02-01

54

1021. Development of a Syrian Hamster Animal Model To Study Replication Competent Adenovirus Vectors for Cancer Gene Therapy  

Microsoft Academic Search

Replication-competent adenovirus vectors for cancer gene therapy are typically evaluated in immunodeficient nude or SCID mice bearing human xenograft tumors. However, the lack of an intact immune system in these animals lessens the relevance of these models to a clinical scenario. We have developed a novel Syrian hamster animal model for the study of oncolytic adenovirus vectors. Initially, we observed

Maria A. Thomas; Jacqueline F. Spencer; Karoly Toth; Marie C. LaRegina; Ann E. Tollefson; Baoling Ying; Mohan Kuppuswamy; Jennifer M. Meyer; Drew L. Lichenstein; Louis A. Zumstein; William S. M. Wold

2005-01-01

55

Experimental Animal Models for Studying Lung Cancer  

Microsoft Academic Search

\\u000a Lung cancer is the leading cause of cancer-related mortality for both men and women worldwide. The use of animal models of\\u000a lung cancer is necessary to improve our understanding of lung tumor biology and facilitate novel therapies and diagnostics.\\u000a To this end, animal models should mimic both the genetic alterations found in human lung tumors and their histological characteristics.\\u000a Currently,

Jiang Liu; Michael R. Johnston

56

Animal carcinogenicity studies: 1. Poor human predictivity.  

PubMed

The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p < 0.0001). The IARC is a leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors. PMID:16522147

Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan

2006-02-01

57

Do algorithm animations assist learning?: an empirical study and analysis  

Microsoft Academic Search

Algorithm animations are dynamic graphical illustrations of computer algorithms, and they are used as teaching aids to help explain how the algorithms work. Although many people believe that algorithm animations are useful this way, no empirical evidence has ever been presented supporting this belief. We have conducted an empirical study of a priority queue algorithm animation, and the study's results

John T. Stasko; Albert N. Badre; Clayton H. Lewis

1993-01-01

58

Developmental Exposure of Mice to TCDD Elicits a Similar Uterine Phenotype in Adult Animals as Observed in Women with Endometriosis  

PubMed Central

Whether environmental toxicants impact an individual woman’s risk for developing endometriosis remains uncertain. Although the growth of endometrial glands and stroma at extra-uterine sites is associated with retrograde menstruation, our studies suggest that reduced responsiveness to progesterone may increase the invasive capacity of endometrial tissue in women with endometriosis. Interestingly, our recent studies using isolated human endometrial cells in short-term culture suggest that experimental exposure to the environmental contaminant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) can alter the expression of progesterone receptor isotypes. Compared to adult exposure, toxicant exposure during development can exert a significantly greater biological impact, potentially affecting the incidence of endometriosis in adults. To address this possibility, we exposed mice to TCDD at critical developmental time points and subsequently examined uterine progesterone receptor expression and steroid responsive transforming growth factor-?2 expression in adult animals. We find that the uterine phenotype of toxicant-exposed mice is markedly similarly to the endometrial phenotype of women with endometriosis.

Nayyar, Tultul; Bruner-Tran, Kaylon L.; Piestrzeniewicz-Ulanska, Dagmara; Osteen, Kevin G.

2007-01-01

59

Biochemical Studies on Acute Hydrazine Toxicity in Mice.  

National Technical Information Service (NTIS)

Two-dimensional paper chromatographic methods were employed to study the changes produced in amino acid distribution in tissues of normal mice, mice treated with hydrazine, and mice pretreated with protective amino acids before injection with hydrazine. T...

E. Roberts D. G. Simonsen

1966-01-01

60

Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice  

Microsoft Academic Search

Routine laboratory procedures, such as handling or transporting animals or carrying out injections on animals, are stressful for animals but are necessary in many pre-clinical studies. Here, the authors show that multiple injections of the non-toxic vehicle cyclodextrin moderately increased plasma corticosterone concentrations in female BALB\\/c mice. Additionally, male BALB\\/c mice that had received a single intraperitoneal injection of harmless

Solveig Drude; Annett Geißler; Jakob Olfe; Astrid Starke; Grazyna Domanska; Christine Schuett; Cornelia Kiank-Nussbaum

2011-01-01

61

Studies on proteins of animal ribosomes  

Microsoft Academic Search

Ribosomes from different tissues and species of animals were tested by several different immunochemical methods. With antisera produced in rabbits by injection of intact ribosomes significant species differences in the antigenic properties of the ribosomes could be demonstrated whereas no tissue conditioned properties in the antigenic determinants were found.

F. Noll; H. Bielka

1970-01-01

62

Wireless microphone for studies of animal vocalizations  

Microsoft Academic Search

Summary A microphone collar for obtaining good quality recordings of animal vocalizations is described. An inexpensive, commercially available wireless microphone was modified and mounted on a collar with a hearing-aidbattery pack. The complete assembly weighs, 25 g, and is readily accepted by domestic cats.

Patricia McKinley; Barbara Dowell; W. M. Schleidt

1976-01-01

63

Lead hepatotoxicology: a study in an animal model.  

PubMed

The increasing use of lead (Pb) for industrial purposes has resulted in the significant increase in environmental contamination of our planet especially in concern to water and food. In this study using the electron scanning microscopy (SEM), the authors showed the effects of this metal as a result of a chronic and cumulative process. As a primary method of detection of Pb in situ, SEM was chosen, coupled with a detection system Noran Voyager of basic microanalysis X-ray (SEM-XRM), with detection system energy dispersive spectrometry. Mice BALB/c was used as a study model. An animal model of inflammation was used, that consisted in the formation of a subcutaneous pocket of air. It was observed that 75% of Pb stock was captured by the liver, the main target organ in the capture of the metal, the kidney was the second organ to capture the Pb stock and the third was the spleen. It was verified that a low deposition of Pb was found in the lungs and the brain. The main results of this study showed how Pb is captured by different organs. We also demonstrated the vulnerability to inflammation of this metal. PMID:21665903

Sá, I; da Costa, M J P; Cunha, E M

2011-06-10

64

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…

Yarden, Hagit; Yarden, Anat

2011-01-01

65

Studying Biotechnological Methods Using Animations: The Teacher’s Role  

Microsoft Academic Search

Animation has great potential for improving the way people learn. A number of studies in different scientific disciplines\\u000a have shown that instruction involving computer animations can facilitate the understanding of processes at the molecular level.\\u000a However, using animation alone does not ensure learning. Students sometimes miss essential features when they watch only animations,\\u000a mainly due to the cognitive load involved.

Hagit YardenAnat Yarden; Anat Yarden

66

Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments.  

PubMed

This study was to investigate a hypothesis that dietary restriction (DR) suppresses learning and memory impairments in dementia animal model SAMP8 mice. Four-week-old female SAMP8 mice were fed either ad libitum (AL) or fed restricted (40% of the food consumed by AL). Results showed that acetylcholine (ACh) levels in hippocampus at aged 12 months of age were 12% higher in DR than that of AL group. Dopamine (DA) and norepinephrine (NE) levels in cerebellum at 8 and 12 months of age were significantly higher (26~94% and 34~43%, respectively) in DR group than those in AL group. Serotonin (5-HT) levels in cerebellum at aged 12 months of age were markedly increased (~53%) in DR group. Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in cerebellum at 8 and 12 months of age were significantly increased (28~41% and 24~64%, respectively) in DR group compared with AL group. In addition, neurotransmitter-related enzymes, choline acetyltransferase (ChAT) and acetylchoinesterase (AChE) activities at 8 and 12 months of age were elevated (6~8% and 5~7%, respectively) in DR group. Monoamine oxidase-B (MAO-B) that catalyzes oxidative deamination in brain were suppressed by 7~10% in DR group. At aged 12 months of age, the generation of basal and induced reactive oxygen species (ROS) in brain significantly decreased by 20% in DR group compared with AL group. These results suggest that inhibitory effect of oxidative stress by DR may play a pivotal role in attenuating the age-related changes observed in dementia animal model SAMP8. PMID:11115807

Kim, D W; Choi, J H

2000-01-01

67

A study in animal ethics in New Brunswick.  

PubMed Central

Society uses animals in ever-increasing numbers and ways, providing ethical challenges. Decisions about animal use are guided by the social consensus ethic towards animals. Because there is no clear social consensus ethic, these decisions are difficult. Society's ethic is changing and a "new ethic" towards animals is emerging. This study addressed the need to better understand society's ethics towards animals. Qualitative research methodology (focus groups) was used to study 7 different animal-interest groups. Qualitative data analysis was computer-aided. The group ethical position towards animals of its own group interest was determined for each group. The animal welfare, companion animal, and veterinary groups took Rollin's Position, a position based on both the Utilitarian and the Rights Principles; the farmer and trapper groups the Utilitarian/Land Ethic position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and preserving the integrity, stability, and beauty of the biotic community; the hunter group the Utilitarian/Judeo-Christian position, a dual position based on actions producing the greatest amount of pleasure and the least amount of pain for the greatest number, and having dominion over animals; and the naturalist group took Rollin's Position/Land Ethic. All these groups perceived medium to extreme ethical responsibility towards animals of their own group's interest that are used by others. The study showed that the predicted "new ethic" towards animals is in New Brunswick society and it is Rollin's Position.

Schneider, B J

2001-01-01

68

Study of Camelpox Virus Pathogenesis in Athymic Nude Mice  

PubMed Central

Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n.) CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c.) infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b+F4/80+ macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c+CD8?+ lymphoid and CD11c+CD11b+ myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog) was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral therapies in an immunodeficiency context.

Duraffour, Sophie; Matthys, Patrick; van den Oord, Joost J.; De Schutter, Tim; Mitera, Tania; Snoeck, Robert; Andrei, Graciela

2011-01-01

69

Study of camelpox virus pathogenesis in athymic nude mice.  

PubMed

Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n.) CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c.) infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b(+)F4/80(+) macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c(+)CD8?(+) lymphoid and CD11c(+)CD11b(+) myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog) was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral therapies in an immunodeficiency context. PMID:21738709

Duraffour, Sophie; Matthys, Patrick; van den Oord, Joost J; De Schutter, Tim; Mitera, Tania; Snoeck, Robert; Andrei, Graciela

2011-06-28

70

Sj?gren's syndrome: studying the disease in mice  

PubMed Central

Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by inflammation of exocrine tissues accompanied by a significant loss of their secretory function. Clinical symptoms develop late and there are no diagnostic tests enabling early diagnosis of SS. Thus, particularly to study these covert stages, researchers turn to studying animal models where mice provide great freedom for genetic manipulation and testing the effect of experimental intervention. The present review summarizes current literature pertaining to both spontaneous and extrinsic-factor induced SS-like diseases in mouse models, discussing advantages and disadvantages related to the use of murine models in SS research.

2011-01-01

71

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.

72

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

73

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.

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

74

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

2013-05-02

75

Reconsideration of insulin signals induced by improved laboratory animal diets, Japanese and American diets, in IRS-2 deficient mice.  

PubMed

Current Japanese and American diets and Japanese diet immediately after the War were converted to laboratory animal diets. As a result, current laboratory animal diet (CA-1, CLEA) unexpectedly resembled the diet of Japanese after the War. This is considered to result in an under-evaluation of diabetes research using laboratory animals at present. Therefore, changes in insulin signals caused by current Japanese and American diets were examined using IRS-2 deficient mice ( IRS2(-/-) mice) and mechanisms of aggravation of type 2 diabetes due to modern diets were examined. IRS2(-/-) mice at 6 weeks of age were divided into three groups: Japanese diet (Jd) group, American diet (Ad) group and CA-1 diet [regular diet (Rd)] group. Each diet was given to the dams from 7 days before delivery. When the IRS2(-/-) mice reached 6 weeks of age, the glucose tolerance test (GTT), insulin tolerance test (ITT) and organ sampling were performed. The sampled organs and white adipose tissue were used for analysis of RNA, enzyme activity and tissues. In GTT and ITT, the Ad group showed worse glucose tolerance and insulin resistance than the Rd group. Impaired glucose tolerance of the Jd group was the same as that of the Rd group, but insulin resistance was worse than in the Rd group. These results were caused an increase in fat accumulation and adipocytes in the peritoneal cavity by lipogenic enzyme activity in the liver and muscle, and the increase in TNFalpha of hypertrophic adipocyte origin further aggravated insulin resistance and the increase in resistin also aggravated the impaired glucose tolerance, leading to aggravation of type 2 diabetes. The Japanese and American diets given to the IRS2(-/-) mice, which we developed, showed abnormal findings in some IRS2(-/-) mice but inhibited excessive reactions of insulin signals as diets used in ordinary nutritional management. PMID:19629935

Hashimoto, H; Arai, T; Mori, A; Kawai, K; Hikishima, K; Ohnishi, Y; Eto, T; Ito, M; Hioki, K; Suzuki, R; Ohsugi, M; Saito, M; Ueyama, Y; Okano, H; Yamauchi, T; Kubota, N; Ueki, K; Tobe, K; Tamaoki, N; Kadowaki, T; Kosaka, K

2009-07-23

76

Animated Versus Static User Interfaces: A Study of Mathsigner  

Microsoft Academic Search

In this paper we report a study aimed at determining the effects of animation on usability and appeal of educational software user interfaces. Specifically, the study compares 3 interfaces developed for the Mathsigner™ program: a static interface, an interface with highlighting\\/sound feedback, and an interface that incorporates five Disney animation principles. The main objectives of the comparative study were to:

Scott Dyer; Nicoletta Adamo-Villani

2008-01-01

77

Dosimetry considerations for animal aerosol inhalation studies  

PubMed Central

The determination of the dose of inhaled aerosol particles in animal subjects is not a trivial exercise. In its simplest form, the dose is the amount (particle number, mass, or other relevant metric) that deposits in the respiratory tract. The amount deposited will depend on the aerosol particle sizes (e.g. the aerodynamic diameter size distribution), the duration of exposure, the exposure system's delivery efficiency, the subject's ventilation rate, the species and strain, and other factors. Similarly, species differences in the clearance rates of deposited particles will influence the time integrated particle doses. In practice, particle doses are estimated using mathematical models, previous experimental dosimetry data, tracers of the inhaled particles, and biomarkers of exposure. With care, desired aerosol doses can be achieved and documented.

PHALEN, ROBERT F.; MENDEZ, LOYDA B.

2010-01-01

78

In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals.  

PubMed

The current study was undertaken to investigate potential oncogenic functions of NanogP8, a tumor-specific retrogene homolog of Nanog (expressed in pluripotent cells), in transgenic animal models. To this end, human primary prostate tumor-derived NanogP8 was targeted to the cytokeratin 14 (K14) cellular compartment, and two lines of K14-NanogP8 mice were derived. The line 1 animals, expressing high levels of NanogP8, experienced perinatal lethality and developmental abnormalities in multiple organs, including the skin, tongue, eye, and thymus in surviving animals. On postnatal day 5 transgenic skin, for example, there was increased c-Myc expression and Ki-67(+) cells accompanied by profound abnormalities in skin development such as thickened interfollicular epidermis and dermis and lack of hypodermis and sebaceous glands. The line 3 mice, expressing low levels of NanogP8, were grossly normal except cataract development by 4-6 mo of age. Surprisingly, both lines of mice do not develop spontaneous tumors related to transgene expression. Even more unexpectedly, high levels of NanogP8 expression in L1 mice actually inhibited tumor development in a two-stage chemical carcinogenesis model. Mechanistic studies revealed that constitutive NanogP8 overexpression in adult L1 mice reduced CD34(+)?6(+) and Lrig-1(+) bulge stem cells, impaired keratinocyte migration, and repressed the expression of many stem cell-associated genes, including Bmp5, Fgfr2, Jmjd1a, and Jun. Our study, for the first time, indicates that transgenically expressed human NanogP8 is biologically functional, but suggests that high levels of NanogP8 may disrupt normal developmental programs and inhibit tumor development by depleting stem cells. PMID:23839044

Badeaux, Mark A; Jeter, Collene R; Gong, Shuai; Liu, Bigang; Suraneni, Mahipal V; Rundhaug, Joyce; Fischer, Susan M; Yang, Tao; Kusewitt, Donna; Tang, Dean G

2013-06-26

79

Animal Models to Study Thyroid Hormone Action in Cerebellum  

Microsoft Academic Search

Thyroid hormone plays a crucial role in the development and functional maintenance of the central nervous system including\\u000a the cerebellum. To study the molecular mechanisms of thyroid hormone action, various animal models have been used. These are\\u000a classified: (1) congenital hypothyroid animals due to thyroid gland dysgenesis or thyroid dyshormonogenesis, (2) thyroid hormone\\u000a receptor (TR) gene-mutated animals, and (3) thyroid

Noriyuki Koibuchi

2009-01-01

80

Design and development of biomimetic quadruped robot for behavior studies of rats and mice  

Microsoft Academic Search

This paper presents the design and development of a novel biomimetic quadruped robot for behavior studies of rats and mice. Many studies have been performed using these animals for the purpose of understanding human mind in psychology, pharmacology and brain science. In these fields, several experiments on social interactions have been performed using rats as basic studies of mental disorders

Hiroyuki ISHII; Yuichi MASUDA; Syunsuke MIYAGISHIMA; S. Fumino; A. Takanishi; C. Laschi; B. Mazzolai; V. Mattoli; P. Dario

2009-01-01

81

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.

Marietta, Eric V.; Murray, Joseph A.

2012-01-01

82

Susceptibility of Mice to Vaginal Infection with Chlamydia trachomatis Mouse Pneumonitis Is Dependent on the Age of the Animal  

Microsoft Academic Search

Mice from three strains, BALB\\/c (H-2 d ), C3H (H-2 k ), and C57BL\\/6 (H-2 b ), ranging from 5 to 14 weeks of age, were inoculated intravaginally with different doses of the Chlamydia trachomatis mouse pneumonitis serovar. Vaginal swabs taken at weekly intervals showed that the percentage of animals with positive cultures and the number of inclusion-forming units recovered

SUKUMAR PAL; ELLENA M. PETERSON; LUIS M. DE LA MAZA

2001-01-01

83

Study of antiseizure effects of Matricaria recutita extract in mice.  

PubMed

Matricaria recutita L. is a well-known medicinal plant that is suggested as being carminative, analgesic, and anticonvulsant in traditional medicine. In the present investigation the effect of hydro-methanolic percolated extract of this plant on seizure induced by picrotoxin was studied in male mice. This study was performed on animals pretreated with doses of 100, 200, and 300 mg/kg of extract or 40 mg/kg phenobarbital as the reference drug via intraperitoneal injection. After 20 min each animal received 12 mg/kg picrotoxin for induction of seizure. Latency of onset time of seizure, duration of seizure, death latency, and death rate were determined in experimental and control groups. The results showed that latency of the beginning time of seizure was increased in groups that were pretreated with different doses of extract. The most effective dose was 200 mg/kg (P < 0.05). In addition, this dose delayed the time of death in mice (P < 0.01). The extract had no effect on the death rate. The results indicate that the extract of M. recutita possesses suitable effects on seizure induced by picrotoxin, and more experiments are needed in this field. PMID:19723069

Heidari, M R; Dadollahi, Z; Mehrabani, M; Mehrabi, H; Pourzadeh-Hosseini, M; Behravan, E; Etemad, L

2009-08-01

84

? ?-Tocopherol on Liver Biochemistry of Endosulfan Intoxicated Mice: A Preliminary Study  

Microsoft Academic Search

The present study was designed to evaluate the protective role of ?-tocopherol (vit.E) against the toxic effects of chlorinated insecticide endosulfan. Forty male albino mice were used as mammalian model in this study. Animals were divided into 4 groups (ten animals each) on the basis of Vitamin-E treatment and endosulfan exposure, Vitamin treatment was started 15 days prior to 1st

Najma Arshad; Gulnaz Shabbir; Shahla Aleem; Muhammad Arshad

85

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...

86

Some Animal Models for the Study of Perinatal Asphyxia  

Microsoft Academic Search

Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered Ê?perfect’ in reflecting the variety and complexity of human

Tonse N. K Raju

1992-01-01

87

The contribution of animal models to the study of obesity  

Microsoft Academic Search

Summary Obesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect

John Speakman; Catherine Hambly; Sharon Mitchell; Elzbieta Krol

2008-01-01

88

Methods for studying habitual behavior in mice  

PubMed Central

Habit formation refers to the process by which goal-directed behavior becomes automatized and less sensitive to changes in the value of the goal. It has clear relevance for our understanding of skill learning and addiction. Recent studies have begun to reveal the neural substrates underlying this process. This article summarizes what is known about the experimental methods used, and provides a protocol for generating and assessing habit formation in mice.

Rossi, Mark A.; Yin, Henry H.

2012-01-01

89

Antioxidant activity of fluoxetine: studies in mice melanoma model.  

PubMed

In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14-day treatment with fluoxetine (10 mg kg(-1) day(-1), i.p.), the endogenous antioxidant non-enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug-protective effect against the melanoma-induced oxidative changes (increased LP and decreased total glutathione (GSH)-level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose-dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma-induced oxidative changes in mice spleen. PMID:20803706

Kirkova, Margarita; Tzvetanova, Elina; Vircheva, Stefani; Zamfirova, Rositsa; Grygier, Beata; Kubera, Marta

2010-08-01

90

Psychology of Animal Cognition: Piagetian Studies  

Microsoft Academic Search

During the last 15 years, Piaget's theory and methods have been used to investigate the cognitive capacities and development of nonhuman primates as well as of a few avian and mammalian species. Most studies have focused on formal testing of object permanence, but data are also available on sensory-motor intelligence, on the concepts of space and causality, and on imitation.

François Y. Doré; Claude Dumas

1987-01-01

91

Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice.  

PubMed Central

In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL-C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in HDL size observed by nondenaturing gradient gel electrophoresis. Turnover studies with doubly labeled HDL showed that dietary fat both increase the transport rate (TR) and decreased the fractional catabolic rate of HDL cholesterol ester (CE) and apo A-I, with the largest effect on HDL CE TR. The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway, perhaps as an adaptation to the metabolic load of a high fat diet. The increase in apo A-I TR by dietary fat was confirmed by experiments showing increased apo A-I secretion from primary hepatocytes isolated from animals on the high fat diet. The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation. The dietary fat-induced decrease in HDL CE and apo A-I fractional catabolic rate may have been caused by the increase in HDL particle size, as was suggested by our previous studies in humans. In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet. Images

Hayek, T; Ito, Y; Azrolan, N; Verdery, R B; Aalto-Setala, K; Walsh, A; Breslow, J L

1993-01-01

92

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

93

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle  

PubMed Central

Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20- to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.

Eliasof, Scott; Lazarus, Douglas; Peters, Christian G.; Case, Roy I.; Cole, Roderic O.; Hwang, Jungyeon; Schluep, Thomas; Chao, Joseph; Lin, James; Yen, Yun; Han, Han; Wiley, Devin T.; Zuckerman, Jonathan E.; Davis, Mark E.

2013-01-01

94

Alternative conceptions in animal classification: A cross-age study  

Microsoft Academic Search

Employing a cross-age design, this study examined students' alternative conceptions in animal classification at the elementary, secondary, and college levels. Based on a previous study that made use of clinical interviews and a classification task, subjects (N = 468) were administered a multiple-choice\\/free-response instrument that probed understanding of the concept animal, the vertebrate\\/invertebrate distinction, and the principal vertebrate classes. Results

John E. Trowbridge; Joel J. Mintzes

1988-01-01

95

Corticosteroid and Neurosteroid Dysregulation in an Animal Model of Autism, BTBR Mice  

PubMed Central

Autism spectrum disorders (ASD) are a constellation of neurodevelopmental disorders associated with disruptions in social, cognitive, and/or motor behaviors. ASD are more prevalent among males than females and characterized by aberrant social and language development, and a dysregulation in stress responding. Levels of progesterone (P4) and its metabolite 5?-pregnan-3?-ol-20-one (3?,5?-THP) are higher and more variable in females compared to males. 3?,5?-THP is also a neurosteroid, which can be rapidly produced de novo in the brain, independent of peripheral gland secretion, and can exert homeostatic effects to modulate stress responding. An inbred mouse strain that has demonstrated an ASD-like behavioral and neuroendocrine phenotype is BTBR T +tf/J (BTBR). BTBR mice have deficits in cognitive and social behavior and have high circulating levels of the stress hormone, corticosterone. We hypothesized that central 3?,5?-THP levels would be different among BTBR mice compared to mice on a similar background C57BL/6J (C57/J) and 129S1/SvlmJ (129S1). Tissues were collected from BTBR, C57/J and 129S1 male mice and levels of corticosterone, P4, and 3?,5?-THP in plasma and hypothalamus, midbrain, hippocampus, and cerebellum were measured by radioimmunoassay. Circulating levels of corticosterone, P4, and 3?,5?-THP were significantly higher among BTBR, than C57/J and 129S1, mice. Levels of P4 in the cerebellum were significantly higher than other brain regions among all mouse strains. Levels of 3?,5?-THP in the hypothalamus of BTBR mice were significantly higher compared to C57/J and 129S1 mice. These findings suggest that neuroendocrine dysregulation among BTBR mice extends to 3?,5?-THP.

Frye, Cheryl A.; Llaneza, Danielle C.

2010-01-01

96

Relevance of experimental animal studies to the human experience  

SciTech Connect

Animal experiments are being used to examine a number of physical and biological factors that influence risk estimations though not usually in coordination with epidemiologists. It is clear that the different mechanisms involved in different types of tumors are reflected in the diversity of dose-response relationships. The forms of the dose-response relationships are influenced by both the initial events and their expression. Evidence is accumulating that many initiated cells do not get expressed as overt cancers and host factors may play a major role in the expression of potential tumor cells. There is a need for information about the relationship of the natural incidence and susceptibility to radiation induction for more tumor types. Such experiments will help answer the question of which risk estimate models are appropriate for different tumor types and can be carried out on animals. Perhaps because of the importance of host factors risk estimates as a percentage of the natural incidence appear to be similar for human beings and mice for a small number of tumor types. The elucidation of the mechanisms involved in different tissues while a slow business remains an important role of animal experiments.

Fry, R.J.M.

1982-01-01

97

Zoophilia in men: a study of sexual interest in animals.  

PubMed

This article presents a study of 114 self-defined zoophile men who were researched primarily through the use of an on-line questionnaire. We describe how the participants acquired the identity label of zoophile, what it meant to them, and their relationships among themselves. Also examined are how they eroticized animals and how human and feral characteristics combined to form this object choice. Finally, participants' sexual profiles with animals and humans, and how the balance of animal and human desires creates different forms of zoophilia, are described. PMID:14574096

Williams, Colin J; Weinberg, Martin S

2003-12-01

98

Animal Models for the Study of Erectile Function and Dysfunction  

Microsoft Academic Search

\\u000a The mechanisms of penile erection have been investigated using animal models from the beginning of modern investigative physiology.\\u000a In 1863, Eckhard reported that electrical stimulation of the nervi erigentes (pelvic nerves) induced penile erection in the\\u000a anesthetized dog. This study identified that erection is a vasodilatory event. Over 125 years of animal experimentation passed\\u000a before the vasodilatory neurotransmitter was identified

Kevin E. McKenna

99

Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo  

PubMed Central

Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Matte, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

2013-01-01

100

Beyond Animal Husbandry: The Study of Farm Animal Cognition and Ensuing Ethical Issues  

Microsoft Academic Search

Concerns about the welfare of agricultural animals in corporate or “factory farming” systems are growing. Increasingly, it is suggested that modern farm animal production practices are morally objectionable, causing physical and mental suffering to animals. Such criticisms are premised on beliefs about the mental capacities of farm animals that are not wholly supported by scientific evidence, for little is known

C. C. Croney; B. Gardner; S. Baggot

2004-01-01

101

Study of hepatitis C virus entry in genetically humanized mice.  

PubMed

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

2012-06-08

102

Laboratory Animals Pulmonary Clearance Study with Chromium 51 Labelled Polystyrene Spherical Particles: Investigations for Clinical Application.  

National Technical Information Service (NTIS)

Polystyrene spherical particles labelled with chromium 51, retaining a small amount of chromium acetylacetonate, were administered through different ways to laboratory animals, mice, rats, dogs and monkeys, in order to work out a suitable technique for cl...

M. Roy H. Metivier R. Masse J. C. Nenot J. Lafuma

1978-01-01

103

Urea Transporter Physiology Studied in Knockout Mice  

PubMed Central

In mammals, there are two types of urea transporters; urea transporter (UT)-A and UT-B. The UT-A transporters are mainly expressed in kidney epithelial cells while UT-B demonstrates a broader distribution in kidney, heart, brain, testis, urinary tract, and other tissues. Over the past few years, multiple urea transporter knockout mouse models have been generated enabling us to explore the physiological roles of the different urea transporters. In the kidney, deletion of UT-A1/UT-A3 results in polyuria and a severe urine concentrating defect, indicating that intrarenal recycling of urea plays a crucial role in the overall capacity to concentrate urine. Since UT-B has a wide tissue distribution, multiple phenotypic abnormalities have been found in UT-B null mice, such as defective urine concentration, exacerbated heart blockage with aging, depression-like behavior, and earlier male sexual maturation. This review summarizes the new insights of urea transporter functions in different organs, gleaned from studies of urea transporter knockout mice, and explores some of the potential pharmacological prospects of urea transporters.

Li, Xuechen; Chen, Guangping; Yang, Baoxue

2012-01-01

104

Viruses and vestibular neuritis: review of human and animal studies.  

PubMed

There is increasing evidence in man and animals that several human viruses can damage the vestibular labyrinth. Clinical and serologic studies of patients with vestibular neuritis suggest that the viruses may play a role in the pathogenesis of this disease. Temporal bone studies of patients dying after vestibular neuritis have found maximal damage in the distal branches of the vestibular nerve. These changes are felt to be consistent with a viral etiology. No satisfactory animal viral model of vestibular neuritis currently exists. However, animal studies have demonstrated that several human viruses including rubeola, herpes simplex, reovirus, mouse and guinea pig cytomegalovirus, and neurotropic strains of influenza A and mumps virus, can infect the vestibular nerve and the vestibular membranous labyrinth. PMID:8470506

Davis, L E

1993-01-01

105

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

106

Alternative conceptions in animal classification: A cross-age study  

NASA Astrophysics Data System (ADS)

Employing a cross-age design, this study examined students' alternative conceptions in animal classification at the elementary, secondary, and college levels. Based on a previous study that made use of clinical interviews and a classification task, subjects (N = 468) were administered a multiple-choice/free-response instrument that probed understanding of the concept animal, the vertebrate/invertebrate distinction, and the principal vertebrate classes. Results suggest that students subscribe to a highly restricted view of animals; applying the label almost exclusively to vertebrates, especially to common mammals. When asked to distinguish between vertebrate and invertebrate animals and to classify several species into vertebrate groups, a wide range of alternative conceptions emerged. Cross-age comparisons indicate that many of these alternative views remain intact throughout the school years, while others yield more readily to formal instruction and/or nonschool experiences. Considered within the context of a neoconstructivist view of learning, several suggestions are offered for teaching concepts in animal classification.

Trowbridge, John E.; Mintzes, Joel J.

107

Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model  

PubMed Central

We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah?/?) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation.

Bissig, Karl-Dimiter; Le, Tam T.; Woods, Niels-Bjarne; Verma, Inder M.

2007-01-01

108

Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model.  

PubMed

We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah(-/-)) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation. PMID:18077355

Bissig, Karl-Dimiter; Le, Tam T; Woods, Niels-Bjarne; Verma, Inder M

2007-12-11

109

Spontaneous Stereotypy in an Animal Model of Down Syndrome: Ts65Dn Mice  

Microsoft Academic Search

Stereotyped behaviors (e.g., body rocking) occur at high rates in individuals with mental retardation (e.g., Down syndrome). To determine if spontaneous stereotypy occurs in a murine model of Down syndrome, the home cage behavior of Ts65Dn and control mice was monitored during the dark cycle. Motor activity was further assessed in novel automated test chambers, with acoustic startle and rotor

Cortney A. Turner; Michael F. Presti; Howard A. Newman; Paul Bugenhagen; Linda Crnic; Mark H. Lewis

2001-01-01

110

Establishment of NOD-Pdcd1-\\/- mice as an efficient animal model of type I diabetes  

Microsoft Academic Search

Mice deficient in programmed cell death 1 (PD-1, Pdcd1), an immunoinhibitory receptor belonging to the CD28\\/cytotoxic T lymphocyte-associated antigen-4 family, spontaneously develop lupus-like autoimmune disease and autoimmune dilated cardiomyopathy on C57BL\\/6 and BALB\\/c backgrounds, respectively. However, how PD-1 deficiency induces different forms of autoimmune diseases on these two strains was unknown. Here, we report that PD-1 deficiency specifically accelerates the

Jian Wang; Taku Yoshida; Fumio Nakaki; Hiroshi Hiai; Taku Okazaki; Tasuku Honjo

2005-01-01

111

Laboratory Animals. Part II. Animals for Research.  

National Technical Information Service (NTIS)

The directory is divided into the following sections: Section I comprises the listings for the common domestic animals (chickens, turkeys, non-inbred mice, inbred mice, hybrid mice, rats, hamsters, guinea pigs, dogs, cats, cattle, goats, sheep, and swine)...

1966-01-01

112

The Use of Animal Models for the Study of FASD  

PubMed Central

Considerable efforts to educate women not to abuse alcohol during pregnancy have failed to reduce the incidence of fetal alcohol syndrome. Therefore, other approaches to limit the impact of prenatal alcohol abuse are under consideration, including the development of preventive and interventional strategies. To provide opportunity for these strategies to be as successful as possible, it is also important to improve methods of identification of affected children. Because of the practical and ethical limitations of utilizing human subjects in prenatal alcohol exposure research, investigators have addressed questions utilizing other biological platforms. This presentation will address more specifically the use of animal models to address three areas of research: the use of animal models to address basic questions about alcohol exposure during development, the use of animal models to improve the identification of affected individuals, and the use of animal models to develop approaches to reduce the impact of prenatal alcohol exposure. The various animal model systems that have been used to study FASD, each with their own specific strengths, have provided new findings that have been successfully extrapolated to human subjects resulting in advancement of the research field and our understanding of FASD.

Wilson, Shannon E.; Cudd, Timothy A.

2011-01-01

113

Fourier transform Raman spectroscopic studies of human and animal skins  

NASA Astrophysics Data System (ADS)

The stratum corneum is the outermost layer of the skin and provides the principal barrier for the ingress of chemicals and environmental toxins into human and animal tissues. However, human skin has several advantages for the administration of therapeutic agents (transdermal drug delivery), but problems occur with the supply, storage, and biohazardous nature of human tissue. Hence, alternative animal tissues have been prepared to model drug diffusion across human skin but the molecular basis for comparison is lacking. Here, FT-Raman spectra of mammalian (human and pig) and reptilian (snake) skins have been obtained and the structural dissimilarities are correlated with drug diffusion studies across the tissues.

Barry, Brian W.; Edwards, Howell G.; Williams, Adrian C.

1994-01-01

114

Intestinal microflora of deep-sea animals: a taxonomic study  

NASA Astrophysics Data System (ADS)

Eleven genera of fish and invertebrates were collected during two cruises to the Puerto Rico Trench. Seventy-nine bacterial isolates were obtained from the intestinal tracts of the animals and 59 from adjacent sediments, organic detritus, and other non-intestinal sources. Using a newly developed taxonomic scheme, a comparative taxonomic study of the 138 cultures indicated few differences in phenotypic characteristics or in generic distribution between the two groups with pseudomonads predominating from both environments. It was concluded that the animal intestinal environment, and not a unique bacterial population contained therein, may be the significant factor in allowing microbial activity in the deep sea. The role the animal intestinal tract may play in this activity is discussed.

Oliver, James D.; Smith, J. Edward

1982-06-01

115

A Mossbauer effect of study of plant and animal fossils  

Microsoft Academic Search

Mossbauer effect (ME) spectroscopy is applied to the study of the mechanism of fossilization process and the effect of environmental conditions on plant and animal fossils. The samples are collected near the Mediterranean Sea in Egypt and Libya. The results indicate that fossilization takes place in two stages: (i) an iron mineral is formed which differs according to the geological

N. A. Eissa; H. A. Sallam; B. A. Ashi; M. Y. Hassan; S. A. Saleh

1976-01-01

116

Zoophilia in Men: A Study of Sexual Interest in Animals  

Microsoft Academic Search

This article presents a study of 114 self-defined zoophile men who were researched primarily through the use of an on-line questionnaire. We describe how the participants acquired the identity label of zoophile, what it meant to them, and their relationships among themselves. Also examined are how they eroticized animals and how human and feral characteristics combined to form this object

Colin J. Williams; Martin S. Weinberg

2003-01-01

117

Dose translation from animal to human studies revisited  

Microsoft Academic Search

As new drugs are developed, it is essen- tial to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allomet- ric dose translations, especially when starting new ani- mal or clinical studies. The need for education regard- ing appropriate translation is evident from the media response regarding some

Shannon Reagan-Shaw; Minakshi Nihal; Nihal Ahmad

2007-01-01

118

Quantification of Cerebral Glucose Metabolic Rate in Mice Using 18F-FDG and Small-Animal PET  

PubMed Central

The aim of this study was to evaluate various methods for estimating the metabolic rate of glucose utilization in the mouse brain (cMRglc) using small-animal PET and reliable blood curves derived by a microfluidic blood sampler. Typical values of 18F-FDG rate constants of normal mouse cerebral cortex were estimated and used for cMRglc calculations. The feasibility of using the image-derived liver time–activity curve as a surrogate input function in various quantification methods was also evaluated. Methods Thirteen normoglycemic C57BL/6 mice were studied. Eighteen blood samples were taken from the femoral artery by the microfluidic blood sampler. Tissue time–activity curves were derived from PET images. cMRglc values were calculated using 2 different input functions (one derived from the blood samples [IFblood] and the other from the liver time–activity curve [IFliver]) in various quantification methods, which included the 3-compartment 18F-FDG model (from which the 18F-FDG rate constants were derived), the Patlak analysis, and operational equations. The estimated cMRglc value based on IFblood and the 3-compartment model served as a standard for comparisons with the cMRglc values calculated by the other methods. Results The values of K1*,k2*,k3*,k4*, and KFDG* estimated by IFblood and the 3-compartment model were 0.22 ± 0.05 mL/min/g, 0.48 ± 0.09 min?1, 0.06 ± 0.02 min?1, 0.025 ± 0.010 min?1, and 0.024 ± 0.007 mL/min/g, respectively. The standard cMRglc value was, therefore, 40.6 ± 13.3 µmol/100 g/min (lumped constant = 0.6). No significant difference between the standard cMRglc and the cMRglc estimated by the operational equation that includes k4* was observed. The standard cMRglc was also found to have strong correlations (r > 0.8) with the cMRglc value estimated by the use of IFliver in the 3-compartment model and with those estimated by the Patlak analysis (using either IFblood or IFliver). Conclusion The 18F-FDG rate constants of normal mouse cerebral cortex were determined. These values can be used in the k4*-included operational equation to calculate cMRglc. IFliver can be used to estimate cMRglc in most methods included in this study, with proper linear corrections applied. The validity of using the Patlak analysis for estimating cMRglc in mouse PET studies was also confirmed.

Yu, Amy S.; Lin, Hong-Dun; Huang, Sung-Cheng; Phelps, Michael E.; Wu, Hsiao-Ming

2009-01-01

119

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

120

Colony formation of C57BL/6J mice in visible burrow system: identification of eusocial behaviors in a background strain for genetic animal models of autism.  

PubMed

Deficits in social interaction are primary characteristics of autism, which has strong genetic components. Genetically manipulated mouse models may provide a useful research tool to advance the investigation of genes associated with autism. To identify these genes using mouse models, behavioral assays for social relationships in the background strains must be developed. The present study examined colony formation in groups of one male and three female mice (Experiment 1) and, groups of three male mice (Experiment 2) of the C57BL/6J strain in a semi-natural visible burrow system. For adult mixed-sex colonies, 4-h observations during both the dark and light cycles for 15 days demonstrated day-dependent increases in huddling together in the chamber accompanied by decreased frequencies of active social behaviors. Sequential analyses of social interactions indicated that approaches to the back of the approached animal typically elicited flight, while approaches to the front of the approached animal failed to do so. This was seen for female to female, and for female to male approaches, as well as male to female approaches, strongly counterindicating a view that rear approach/flight specifically reflects female responsivirity to unwanted male sexual approach. For adult male colonies, similar protocols found that these social behaviors were similar to those of adult mixed-sex colonies. These findings suggest two potentially useful measures of eusocial behavior in mice, of possible value for genetic mouse models of autism; that is, huddling together and approaches to the front but not the back, of conspecifics. PMID:16971001

Arakawa, Hiroyuki; Blanchard, D Caroline; Blanchard, Robert J

2006-09-12

121

Humanized mice for the study of type 1 diabetes and beta cell function.  

PubMed

Our understanding of the basic biology of diabetes has been guided by observations made using animal models, particularly rodents. However, humans are not mice, and outcomes predicted by murine studies are not always representative of actual outcomes in the clinic. In particular, investigators studying diabetes have relied heavily on mouse and rat models of autoimmune type 1-like diabetes, and experimental results using these models have not been representative of many of the clinical trials in type 1 diabetes. In this article, we describe the availability of new models of humanized mice for the study of three areas of diabetes. These include the use of humanized mice for the study of (1) human islet stem and progenitor cells, (2) human islet allograft rejection, and (3) human immunity and autoimmunity. These humanized mouse models provide an important preclinical bridge between in vitro studies and rodent models and the translation of discoveries in these model systems to the clinic. PMID:19120266

King, Marie; Pearson, Todd; Rossini, Aldo A; Shultz, Leonard D; Greiner, Dale L

2008-12-01

122

Blood compatible microfluidic system for pharmacokinetic studies in small animals.  

PubMed

New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection. PMID:23000896

Convert, Laurence; Baril, Frédérique Girard; Boisselle, Vincent; Pratte, Jean-François; Fontaine, Réjean; Lecomte, Roger; Charette, Paul G; Aimez, Vincent

2012-11-21

123

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.

124

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

125

Current Animal Models: Transgenic Animal Models for the Study of Measles Pathogenesis  

Microsoft Academic Search

Animal models are highly important to understand the pathologic mechanisms of viral diseases. Therefore, the lack of a suitable\\u000a animal model has greatly hindered the research into the pathogenesis of measles. Identification of two human receptors for\\u000a measles virus, CD46 and CD150 (SLAM) has opened new perspectives in this field. During the last decade, numerous transgenic\\u000a animal models have been

C. I. Sellin; B. Horvat

126

Toxicology and carcinogenesis studies of microencapsulated citral in rats and mice.  

PubMed

Citral, a widely used natural ingredient, 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 citral in the feed for 14 weeks or two years. All studies included untreated and vehicle control groups. In the 14-week studies, rats and mice were given diets containing 3,900, 7,800, 15,600, or 31,300 ppm citral. In rats, food consumption was reduced in the two highest dose groups. In mice an apparent increase in food consumption was observed, but was due to mice scattering the feed. Body weights of all treated animals were less than controls. All rats and four male mice were killed moribund in the high dose groups. In rats, forestomach and kidney lesions were observed. At the higher doses, lesions observed in the bone marrow, testes, and thymus in rats and in the ovary in mice were considered related to inanition and resultant moribundity. In the two-year studies, rats were exposed to 1,000, 2,000, or 4,000 ppm citral. Body weights were reduced in the 4,000 ppm rats. Mice were exposed to 500, 1,000, or 2,000 ppm citral. Body weights in the 1,000 and 2,000 ppm groups were reduced. No neoplasms were attributed to citral in rats or mice. Malignant lymphoma occurred with a positive trend and was significantly greater than controls in female mice in the 2,000 ppm group. However, the incidences were within the NTP historical control range and could not be clearly related to citral administration. PMID:12563105

Ress, N B; Hailey, J R; Maronpot, R R; Bucher, J R; Travlos, G S; Haseman, J K; Orzech, D P; Johnson, J D; Hejtmancik, M R

2003-02-01

127

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

2012-10-26

128

Study of interaction of tramadol with amlodipine in mice  

PubMed Central

Objective: To study a possible interaction between tramadol, an opioid analgesic and amlodipine, a dihydropyridine calcium channel blocker with proposed antinociceptive property. Materials and Methods: Albino mice of Haffkine strain were used for the study. The experiment was carried out using tail-flick method. Different doses of tramadol (50 mg/kg, 22.8 mg/kg and 10 mg/kg) were administered intraperitoneally to select the nonanalgesic dose. The animals were treated with different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg, 3.5 mg/kg) to study its antinociceptive action. Combination of different doses of both the drugs were administered to study antinociceptive effect of the combination. Results: Tramadol, showed dose dependent antinociception which persisted for entire two hours of the study period. Antinociceptive action was seen with amlodipine at a dose of 3.5 mg/kg. Different doses of amlodipine (2.5 mg/kg, 3.0 mg/kg) in combination with the nonanalgesic dose of tramadol (10 mg/kg) produced a significant enhancement of antinociceptive effect of tramadol. Combination of 3.5 mg/kg dose of amlodipine with nonanalgesic dose of tramadol (10 mg/kg) further enhances antinociceptive activity. Conclusion: It is concluded that combination of amlodipine, a N - type calcium channel blocker, with tramadol produce significant enhancement of antinociceptive activity of tramadol.

Modi, Hiral; Mazumdar, Bipa; Bhatt, Jagatkumar

2013-01-01

129

Evaluation of the experimental inoculation of Cryptococcus albidus and Cryptococcus laurentii in normal mice: virulence factors and molecular profile before and after animal passage.  

PubMed

The genus Cryptococcus includes free-developing species, a few of which are of medical importance. Some, such as C. neoformans and C. gattii, cause infections in man frequently and C. albidus and C. laurentii cause less so. The aims of this study were to evaluate organ colonization after inoculation of C. albidus and C. laurentii isolates in normal BALB/c mice, the virulence factors (growth at 37 degrees C, capsule, melanin, proteinase, and phospholipase production) and the molecular profile (PCR-fingerprinting) of the yeasts before and after infection. The importance of different profiles (virulence and molecular) was considered in relation to the distribution in different organs and to the time intervals of isolation from organs. C. albidus was isolated from animal organs 2 to 10 days after inoculation and C. laurentii from 2 to 120 days. Most isolates of the two species kept the virulence factors showed before inoculation. The high homogeneity of the molecular profile of C. albidus and the high heterogeneity of C. laurentii were kept through the passages in animals. It is concluded that most isolates of both species were recovered from the animal organs after 5 or more days, and phenotypes were not altered by inoculation. No molecular alteration was detected and the virulence factors were not related to the time intervals before isolation from organs. PMID:19363657

Pedroso, Reginaldo dos Santos; Ferreira, Joseane Cristina; Lavrador, Marco Aurélio Sicchiroli; Maffei, Claudia Maria Leite; Candido, Regina Celia

2009-04-11

130

Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice  

PubMed Central

Background and purpose: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice. Experimental approach: Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice. Key results: NPS (0.01–1?nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5?mg?kg?1). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15?mg?kg?1) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively. Conclusions and implications: We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.

Rizzi, A; Vergura, R; Marzola, G; Ruzza, C; Guerrini, R; Salvadori, S; Regoli, D; Calo, G

2008-01-01

131

Towards environmental construct validity in animal models of CNS disorders: optimizing translation of preclinical studies.  

PubMed

There is an enormous demand for new therapeutic interventions for a range of major disorders. The majority of clinical trials in recent years have been unsuccessful despite highly promising preclinical data. Therefore, an urgent issue confronting both the academic and commercial medical research sectors is how to optimize translation of preclinical studies. The vast majority of preclinical studies are currently performed using laboratory mice and rats. We will discuss the various opportunities for optimization of animal models of CNS disorders. One limitation of current approaches is that most studies are conducted on sedentary, unstimulated animals with unlimited access to food in the home cage, thus leading to metabolic and physiological compromise. Environmental enrichment, which enhances sensory stimulation, cognitive activity and physical exercise, has been demonstrated to induce dramatic effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. Environmental enrichment also exerts beneficial effects outside the CNS, such as a reduction in excess body fat. We propose that therapeutic interventions which are found to show promise in standard-housed preclinical models should be subsequently tested under conditions of greater environmental enrichment to identify therapeutics which continue to show efficacy in housing contexts of superior 'environmental construct validity'. Other possible approaches to optimize the quality, validity and reporting of preclinical studies in animal models are also discussed. PMID:23574171

Burrows, Emma L; Hannan, Anthony J

2013-08-01

132

Transgenic animal models of neurodegeneration based on human genetic studies  

PubMed Central

The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease.

Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko

2011-01-01

133

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.

Abdussalam, M.

1959-01-01

134

ELF magnetic fields: animal studies, mechanisms of action.  

PubMed

Animal studies can contribute to addressing the issue of possible greater health risk for children exposed to 50-60 Hz extremely low frequency (ELF) magnetic fields (MFs), mostly in terms of teratological effects and cancer. Teratology has been extensively studied in animals exposed to ELF MFs but experiments have not established adverse developmental effects. Childhood leukaemia has been the only cancer consistently reported in epidemiological studies as associated with exposure to ELF MFs. This association has been the basis for the classification as "possibly carcinogenic to humans" by the International Agency for Research on Cancer in 2002. Animal experiments have provided only limited support for these epidemiological findings. However, none but one study used an animal model for acute lymphoblastic leukaemia (ALL), the main form of childhood leukaemia, and exposures to ELF MFs were not carried out over the whole pregnancy period, when the first hit of ALL is assumed to occur. Moreover, there are no generally accepted biophysical mechanisms that could explain carcinogenic effects of low-level MFs. The radical pair mechanism and related cryptochromes (CRY) molecules have recently been identified in birds and other non-mammalian species, as a sensor of the geomagnetic field, involved in navigation. The hypothesis has to be tested in mammalian models. CRY, which is part of the molecular circadian clock machinery, is a ubiquitous protein likely to be involved in cancer cell growth and DNA repair. In summary, we now have some clues to test for a better characterization of the interaction between ALL and ELF MFs exposure. PMID:21914452

Lagroye, Isabelle; Percherancier, Yann; Juutilainen, Jukka; De Gannes, Florence Poulletier; Veyret, Bernard

2011-09-08

135

KTP-532 laser-assisted microvascular anastomosis (experimental animal study)  

Microsoft Academic Search

Former animal studies on laser-assisted microvascular anastomosis performed with CO2-, argon-, diode-, Holmium:YAG- and Nd:YAG-lasers had already proven the stability of the anastomotic sites. Tissue damage remained\\u000a minimal along the anastomosis, while duration of the surgeries decreased significantly compared to that of traditionally implemented\\u000a microvascular sutures. In addition to this, foreign body reaction next to end-to-end anastomosis appeared to be

Balázs B. L?rincz; Endre Kálmán; Imre Gerlinger

2007-01-01

136

Apolipoprotein E and atherosclerosis: insight from animal and human studies  

Microsoft Academic Search

Major advances have been made in our understanding of the role of apolipoprotein E (apoE) in the onset and development of atherosclerosis. Increasing evidence from both animal and human studies suggests that apoE is able to protect against atherosclerosis by: a) promoting efficient uptake of triglyceride-rich lipoproteins from the circulation; b) maintaining normal macrophage lipid homeostasis; c) playing a role

Jean Davignon; Jeffrey S. Cohn; Laurence Mabile; Lise Bernier

1999-01-01

137

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.  

PubMed

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents. PMID:12750232

Corpet, Denis E; Pierre, Fabrice

2003-05-01

138

Social Fear Conditioning: A Novel and Specific Animal Model to Study Social Anxiety Disorder  

PubMed Central

Social anxiety disorder (SAD) is a major health concern with high lifetime prevalence. The current medication is rather unspecific and, despite considerable efforts, its efficacy is still unsatisfactory. However, there are no appropriate and specific animal models available to study the underlying etiology of the disorder. Therefore, we aimed to establish a model of specific social fear in mice and use this social fear conditioning (SFC) model to assess the therapeutic efficacy of the benzodiazepine diazepam and of the antidepressant paroxetine; treatments currently used for SAD patients. We show that by administering electric foot shocks (2–5, 1?s, 0.7?mA) during the investigation of a con-specific, the investigation of unfamiliar con-specifics was reduced for both the short- and long-term, indicating lasting social fear. The induced fear was specific to social stimuli and did not lead to other behavioral alterations, such as fear of novelty, general anxiety, depression, and impaired locomotion. We show that social fear was dose-dependently reversed by acute diazepam, at doses that were not anxiolytic in a non-social context, such as the elevated plus maze. Finally, we show that chronic paroxetine treatment reversed social fear. All in all, we demonstrated robust social fear after exposure to SFC in mice, which was reversed with both acute benzodiazepine and chronic antidepressant treatment. We propose the SFC model as an appropriate animal model to identify the underlying etiology of SAD and possible novel treatment approaches.

Toth, Iulia; Neumann, Inga D; Slattery, David A

2012-01-01

139

Animals, Animals, Animals  

NSDL National Science Digital Library

Third grade students may use this page for additional resources for their animal research. Use these links as part of your animal research: Desert Biome What Swims Beneath: Creatures of the Sea Scaly Surprises (ScienceWorld) Manatees AnimalPlanet.com: Mammal Guide Endangered Species Picture Book MIKIDS!: Mammals ZOOM MAMMALS - EnchantedLearning.com Smithsonian National Zoological Park Enchanted Learning: Zoom Sharks Shark School Sharks: Did You Know? Sharks: Myth and Mystery The Secret World of Sharks and Rays ...

Laz, Mrs.

2006-12-16

140

Further studies on cyclic erythropoiesis in mice  

SciTech Connect

When young adult female W/Wv mice are given 0.5 micro+Ci /sup 89/Sr/g body weight intravenously, their hematocrit values oscillate from nadirs of 26% to zeniths of 42% with a periodicity of 16 days. The response of the W/Wv mouse to an assortment of radioactive and hematologic stresses have been examined in an effort to understand better the pathophysiology of cyclic erythropoiesis. When the dose of /sup 89/Sr is increased, the amplitude of cycling increases as nadirs are lowered, but periodicity is unchanged. When the dose of /sup 89/Sr is lowered to 0.3 microCi or less, cyclic erythropoiesis of substantial amplitude is observed only after five or six microoscillations. A single hematopoietic insult of 80 rad x-irradiation coupled with phlebotomy produces a transient form of cyclic erythropoiesis, namely, a series of dampened oscillations prior to recovery. Finally, we report that Wv/Wv mice exhibit a form of cyclic erythropoiesis in response to 0.5 microCi /sup 89/Sr/g body weight, in which the hematocrit values of successive nadirs gradually increase, and stabilize at about 100 days. /sup 89/Sr does not induce cyclic erythropoiesis in the +/+, W/+, or W/v/+ mice, the Hertwig strain of anemic mice, or in normal BDF1 mice.

Gibson, C.M.; Gurney, C.W.; Simmons, E.L.; Gaston, E.O.

1985-10-01

141

Longitudinal studies of chromosomal abnormalities and reticulum cell proliferation in New Zealand Black mice.  

PubMed

A longitudinal study of 40 New Zealand Black (NZB) mice and 20 BALB/c control animals was performed. A significant association was observed between the presence of acquired spleen-cell aneuploidy at some time during life and development of histological evidence of reticulum-cell neoplasia in individual animals. This finding is compatible with the hypothesis that aneuploid clones which arise in the spleens of aging NZBs are at least potentially neoplastic. However, no relationship between histologically neoplastic reticulum cell proliferation and aneuploidy was apparent in single splenic specimens obtained from NZB mice of various ages. This lack of association indicates that failure to detect chromosomal abnormalities on direct study of cells from a tumor cannot be taken as evidence that the neoplastic cells themselves lack such abnormalities. PMID:359488

Friedman, J M; Fialkow, P J; East, J; Bryant, J I; Salo, A C

1978-10-15

142

Pathological Aspects of Spontaneous Uveitis and Retinopathy in HLA-A29 Transgenic Mice and in Animal Models of Retinal Autoimmunity: Relevance to Human Pathologies  

Microsoft Academic Search

Purpose: A major increased risk of developing birdshot chorioretinopathy is reported in humans who are HLA-A29-positive. To better characterize this disease, an animal model of HLA-A29-associated disease was developed and the pathology arising spontaneously in these transgenic mice was compared to animal models of autoimmune uveoretinitis and to human pathology. Materials and Methods: HLA-A2902 cDNA (A29c) was obtained from a

Yvonne de Kozak; Serge Camelo; Marika Pla

2008-01-01

143

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

144

Detection of ICAM-1 in Experimentally Induced Colitis of ICAM-1-deficient and Wild-type Mice: An Immunohistochemical Study  

Microsoft Academic Search

Adhesion molecules (e.g. ICAM-1, CD 54) are known to be upregulated on activated vascular endothelial cells during inflammatory reactions. To study the role of ICAM-1 in intestinal inflammation in vivo, we induced acute experimental colitis in wild-type (C57BL\\/6) mice and ICAM-1-deficient mice, by feeding the animals with 3% dextran sodium sulphate (DSS) in drinking water for 7 days. In the

Farid Bendjelloul; Pavel Rossmann; Petr Malý; Václav Mandys; Marie Jirkovská; Ludmila Prokešová; Ludmila Tu?ková; Helena Tlaskalová-Hogenová

2000-01-01

145

Estimation of the 18F-FDG Input Function in Mice by Use of Dynamic Small-Animal PET and Minimal Blood Sample Data  

PubMed Central

Derivation of the plasma time–activity curve in murine small-animal PET studies is a challenging task when tracers that are sequestered by the myocardium are used, because plasma time–activity curve estimation usually involves drawing a region of interest within the area of the reconstructed image that corresponds to the left ventricle (LV) of the heart. The small size of the LV relative to the resolution of the small-animal PET system, coupled with spillover effects from adjacent myocardial pixels, makes this method reliable only for the earliest frames of the scan. We sought to develop a method for plasma time–activity curve estimation based on a model of tracer kinetics in blood, muscle, and liver. Methods Sixteen C57BL/6 mice were injected with 18F-FDG, and approximately 15 serial blood samples were taken from the femoral artery via a surgically inserted catheter during 60-min small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. We constructed a 5-compartment model designed to predict the plasma time–activity curve of 18F-FDG by use of data from a minimum of 2 blood samples and the dynamic small-animal PET scan. The plasma time–activity curve (TACp) was assumed to have 4 exponential components (TACP = A1e?1t + A2e?2t + A3e?3t ? (A1 + A2 + A3) e?4t) based on the serial blood samples. Using Bayesian constraints, we fitted 2-compartment submodels of muscle and liver to small-animal PET data for these organs and simultaneously fitted the input (forcing) function to early small-animal PET LV data and 2 blood samples (~10 min and ~1 h). Results The area under the estimated plasma time–activity curve had an overall Spearman correlation of 0.99 when compared with the area under the gold standard plasma time–activity curve calculated from multiple blood samples. Calculated organ uptake rates (Patlak Ki) based on the predicted plasma time–activity curve had a correlation of approximately 0.99 for liver, muscle, myocardium, and brain when compared with those based on the gold standard plasma time–activity curve. The model was also able to accurately predict the plasma time–activity curve under experimental conditions that resulted in different rates of clearance of the tracer from blood. Conclusion We have developed a robust method for accurately estimating the plasma time–activity curve of 18F-FDG by use of dynamic small-animal PET data and 2 blood samples.

Ferl, Gregory Z.; Zhang, Xiaoli; Wu, Hsiao-Ming; Kreissl, Michael C.; Huang, Sung-Cheng

2012-01-01

146

[Studies on quality and safety control of drugs for human use from transgenic animals/clone animals].  

PubMed

Recently the pharmaceuticals, which were produced using transgenic animals, have been developed, and will be submitted for registration in nearly future in Japan as well as in USA and EU. In addition, clone animals are also thought to be useful for the productions of the pharmaceuticals. This study has been, therefore, undertaken to establish the technical requirement for registration of the pharmaceuticals. They should be evaluated from the following standpoints: 1) Transgene construct and its characterization; 2) Creation and characterization of the transgenic founder animal; 3) Establishment of a reliable and continuous source of transgenic founder animals; 4) Generation and selection of the production animals; 5) Maintenance of transgenic animals; 6) Recovery and purification of products from transgenic animals; 7) Characterization of products; 8) Process validation/evaluation and in-process test; 9) Specification of products; 10) Stability of products; 11) Preclinical safety evaluation and clinical evaluation. Cloning technology by nuclear transfer of a transformed somatic cell has been already applied to the creation of the transgenic founder animal for the production of pharmaceuticals. The pharmaceuticals produced using the clone animals could be evaluated from almost the same standpoints. However, the flexible evaluation will be also needed depending on the development of the technology. PMID:11915277

Hayakawa, T; Toyoshima, S; Yamaguchi, T; Kawanishi, T

2001-01-01

147

Mycobiota and Ochratoxin A in laboratory mice feed: preliminary study  

Microsoft Academic Search

The occurrence of mycotoxin-producing moulds in animal feed is a hazard for animals. When these undesirable substances contaminate\\u000a laboratory animal feed, convey an additional problem in experimental animal assays confidence levels. The aim of this study\\u000a was to evaluate fungal contamination and to determine natural occurrence of Ochratoxin A (OTA) in 31 samples. OTA is a mycotoxin\\u000a produced by fungi

Inês Almeida; H. Marina Martins; Marta F. Marques; Salomé Magalhães; Fernando Bernardo

2010-01-01

148

STUDIES ON HERPETIC INFECTION IN MICE  

PubMed Central

Passive immunity, naturally acquired from immune mothers or artificially induced through the administration of immune rabbit serum, conferred on suckling mice of the albino Swiss strain a high degree of resistance against herpetic infection following the intranasal instillation of the virus. Antibodies, which could be readily demonstrated in the blood of 2-week-old mice, were received by the offspring of immune mothers primarily by the mammary route. Naturally acquired immunity declined rapidly when suckling was interrupted. Herpes virus was not recovered from the fetuses of either immune or infected, non-immune mothers.

Berry, George Packer; Slavin, Howard B.

1943-01-01

149

Study of morphine-induced dependence in gonadectomized male and female mice  

Microsoft Academic Search

In this study we evaluated the effects of sex difference and also sex hormones on the naloxone-precipitated morphine withdrawal in both orchidectomized (ORC) male and ovariectomized (OVX) female mice. Morphine (50, 50 and 75 mg\\/kg\\/day for 4 days, s.c.) was administered to animals and at 5th day naloxone (4 mg\\/kg, i.p.)-precipitated morphine withdrawal signs, jumpings and the percentage of weight loss, were measured.

Mahsa Sadeghi; Setareh Sianati; Dina Kalbasi Anaraki; Mehdi Ghasemi; Mehrak Javadi Paydar; Behrang Sharif; Shahram Ejtemaei Mehr; Ahmad Reza Dehpour

2009-01-01

150

Preliminary study of the effect of repeated motor training on spatial learning ability in adult lurcher mutant mice.  

PubMed

Lurcher mutant mice represent a model of olivocerebellar degeneration. They suffer from cerebellar ataxia and deterioration of cognitive functions. The aim of the work was to study the effect of repetitive enforced motor training on spatial learning ability and motor coordination in adult Lurcher mutant mice of the C57BI strain. Experimental mice were trained repetitively on a rotarod. Control mice were left without the training. Motor coordination was tested four times-before the training, in the third week of the training, at the end of the training and after a spatial learning test following the training. A rotarod of higher cylinder diameter and lower rotation speed was used. Spatial learning was examined using the Morris water maze. Trained animals achieved significantly better results than untrained mice in the 2nd and 3rd motor coordination test. In the last test following the spatial learning examination, untrained mice improved their performances so that there were no differences between trained and untrained group. In the Morris water maze trained mice showed higher spatial learning ability than untrained animals. Motor coordination capability of adult Lurcher mutant mice was improved by the training on rotarod but also by swimming during the experiment in the water maze. Repetitive motor activity led to increase of spatial learning ability. PMID:17682726

Cendelín, J; Korelusová, I; Vozeh, F

2007-01-01

151

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.”

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

2012-01-01

152

Using computational and mechanical models to study animal locomotion.  

PubMed

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

2012-09-16

153

Human and animal studies of schizophrenia-related gating deficits.  

PubMed

Prepulse Inhibition (PPI) of the startle response and the P50 auditory-evoked potential suppression are used to assess impairments in the regulation of the neural substrates and to determine the clinical significance of inhibitory deficits in schizophrenia. The study of gating deficits in schizophrenia and in related animal model studies have already advanced our understanding of the neural substrates of information processing abnormalities in patients with schizophrenia. Individuals with schizotypal personality disorder as well as clinically unaffected family members of patients with schizophrenia show PPI and P50 suppression deficits. These "schizophrenic spectrum" populations are not grossly psychotic, nor are they receiving antipsychotic medications. Therefore, the gating deficits are presumed to reflect core (eg, intermediate phenotypic) schizophrenia-linked information processing abnormalities. Several studies have reported that gating deficits are associated with clinical ratings of psychiatric symptoms, thought disorder, and neuropsychologic deficits in patients with schizophrenia. In addition, recent human pharmacologic studies have indicated that gating deficits can be reversed by rationally-selected compounds. Animal model studies have generally shown convergence with the human studies and may lead to improved identification of efficacious new antipsychotic medications for patients with schizophrenia. PMID:11122903

Light, G A; Braff, D L

1999-10-01

154

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

2013-06-21

155

Electromyographic studies in mdx and wild-type C57 mice.  

PubMed

The electromyographic (EMG) characteristics of human Duchenne muscular dystrophy (DMD) have been well-described. However, to our knowledge, no prior needle electromyographic (EMG) studies of motor unit morphology have been undertaken in muscles from the mdx mouse, an animal that is genetically homologous to DMD. There are significant phenotypic differences between the human and murine dystrophic conditions, bringing into question whether the mdx mouse is an appropriate animal model for DMD. This study was done in order to characterize the EMG findings in mdx mice, compared to normal wild-type mice, and to assess for similarities to DMD. The tibialis anterior and gastrocnemius/soleus muscles from 34 mice (16 C57 wild-type and 18 mdx), divided into four age groups (3, 12, 18, and 24 months), were examined. Wild-type muscles showed normal insertional activity and no abnormal activity at rest. Motor unit action potential (MUAP) parameters were characterized. In contrast to wild-type muscles, mdx muscles showed increased insertional activity, abnormal spontaneous potentials, and the presence of complex repetitive discharges (CRDs). MUAPs showed increased numbers of phases (4.0 +/- 0.6, P < 0.001) and duration (7.1 +/- 1.2 ms, P < 0.02), as well as late components (15%). These EMG data indicate that mdx muscles display EMG characteristics similar to those found in muscles from boys with DMD, lending credence to the mdx mouse as an animal model for this disease. The data obtained in this study indicate a potential role for EMG as an in vivo, objective measurement tool that could be used longitudinally to monitor the effects of therapeutic interventions in mdx mice. This is important as there are few objective measures of muscle function in murine models that do not require killing the animal. PMID:16281275

Han, Jay J; Carter, Gregory T; Ra, Jennifer J; Abresch, R Ted; Chamberlain, Jeffrey S; Robinson, Lawrence R

2006-02-01

156

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

157

20 years studying p53 functions in genetically engineered mice  

Microsoft Academic Search

Cell and molecular biological studies of p53 functions over the past 30 years have been complemented in the past 20 years by studies that use genetically engineered mice. As expected, mice that have mutant Trp53 alleles usually develop cancers of various types more rapidly than their counterparts that have wild-type Trp53 genes. These mouse studies have been instrumental in providing

Lawrence A. Donehower; Guillermina Lozano

2009-01-01

158

Anabolic androgenic steroids and aggression: studies using animal models.  

PubMed

The use of anabolic androgenic steroids (AASs) has escalated in teenagers and is associated with increased violence. Adolescent exposure to chronic high levels of AASs is of particular concern because puberty is a hormonally sensitive period during which neural circuitry for adult male patterns of behavior develop. Thus, teenage AAS use may have long-term repercussions on the potential for displaying aggression and violence. Animal models have contributed valuable information on the effects of AAS use. For example, studies in rodents confirmed that exposure to the AASs testosterone and nandrolone, but not stanozolol, does indeed increase aggression. A side effect of AAS use reported in humans is "'roid rage," characterized by indiscriminate and unprovoked aggression. Results of animal studies demonstrated that pubertal rats receiving AASs respond appropriately to social cues as they are more aggressive toward intact males than are castrates. Also, testosterone-treated males recognize appropriate environmental cues as they are most aggressive in their home cage. Thus, adolescent AAS exposure increases aggressive behaviors, but does not induce indiscriminate aggression. To assess whether AAS exposure increases aggression after provocation, rats were tested following a mild tail-pinch. In adolescent males, provocation increased aggression after withdrawal from testosterone, nandrolone, and stanozolol, an effect which persisted for many weeks. The data suggest that AASs sensitize animals to their surroundings and lower the threshold to respond to provocation with aggression. Thus, in humans, pubertal AAS exposure may not cause violent behaviors, but may increase the likelihood that aggressive acts will result in violence. This may persist into adulthood. PMID:15817752

McGinnis, Marilyn Y

2004-12-01

159

Animal models of autism spectrum disorder (ASD): a synaptic-level approach to autistic-like behavior in mice.  

PubMed

Autism spectrum disorder (ASD) is one of the most common neurodevelopmental disorders and is thought to be closely associated with genetic factors. It is noteworthy that many ASD-associated genes reported by genome-wide association studies encode proteins related to synaptic formation, transmission, and plasticity. Therefore, it is essential to elucidate the relationship between deficiencies in these genes and the relevant ASD-related phenotypes using synaptic and behavioral phenotypic analysis of mice that are genetically modified for genes related to ASD (e.g., knockout or mutant mice). In this review, we focus on the behavioral-, cellular-, and circuit-level phenotypes, including synaptic formation and function, of several knockout mouse models with genetic mutations related to ASD. Moreover, we introduce our recent findings on the possible association of the dense-core vesicle secretion-related gene CAPS2/CADPS2 with ASD by using knockout mice. Finally, we discuss the usefulness and limitations of various mouse models with single gene mutations for understanding ASD. PMID:23615300

Shinoda, Yo; Sadakata, Tetsushi; Furuichi, Teiichi

2013-01-01

160

Radioprotectors and Tumors: Molecular Studies in Mice  

SciTech Connect

This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

Gayle Woloschak, David Grdina

2010-03-10

161

Cortical bone composition and orientation as a function of animal and tissue age in mice by Raman spectroscopy.  

PubMed

Important aspects of bone tissue quality include the physicochemical properties of its main constituents, the organic matrix and the mineral crystals. One of the most commonly reported measurements of Raman analysis of bone is the mineral to matrix ratio, obtained from the ratio of the integrated areas of any of the phosphate and amide peaks which depend on both tissue organization and composition. Cube-like samples of normal mouse cortical bone taken from the diaphysis and metaphysis of the femur were investigated within different age groups (2, 4, 8 and 12 weeks) by Raman microspectroscopy. Anatomically identical bone in both longitudinal and transverse directions was analyzed, enabling the discrimination between orientation and composition changes both as a function of animal age, and tissue age within the same animal. The results of the present study indicate that there is a parallel evolution of both orientation and chemical composition as a function of animal age, as well as tissue age within the same specimen. Our tissue age modified ratio of the carbonate to phosphate Raman peaks suggests that the bone mineral crystallite maturity remains relatively constant with animal age. Comparisons of polarized and depolarized experiments in the transversal plane of the diaphysis show a lack of orientation effects as a function of tissue age within the same animal, but exhibit differences as a function of animal age. In the metaphysis, the orientation effect is evident too, albeit less pronounced. This is most likely due to either the age difference between the two tissues within the same specimen in the long bone axis, as metaphyseal bone is generally younger than diaphyseal, or the more random orientation of the tissue collagen itself. PMID:20450992

Gamsjaeger, Sonja; Masic, A; Roschger, P; Kazanci, M; Dunlop, J W C; Klaushofer, K; Paschalis, E P; Fratzl, P

2010-05-05

162

ACTIVE ANAPHYLAXIS TO A FOREIGN PROTEIN INDUCED IN MICE BY THE TRANSFER OF TISSUE FROM ANIMALS PREVIOUSLY INJECTED WITH THE PROTEIN  

PubMed Central

Following single intravenous injections of a foreign protein antigen, bovine ?-globulin, into mice and rabbits, antigenic material persisting in the liver could be detected for several weeks. Ground liver tissue—taken from the mice and rabbits, just mentioned, either 4 or 6 weeks after injecting the antigen—when transferred repeatedly, at 2 or 3 day intervals, to the peritoneal cavities of normal, or unilaterally adrenalectomized, recipient mice, rendered the recipients sensitive to active anaphylaxis when they were challenged after a suitable interval by intravenous injections of the original antigen. The work throws some light on the state of the antigenic material that persists for 4 to 6 weeks in the livers of the donor animals. Obviously it is sufficiently unchanged, at least in its reactive groups, to engender in the recipient mice antibodies capable of reacting with the original antigen.

McMaster, Philip D.; Edwards, Joshua L.; Sturm, Ernest

1955-01-01

163

Implicit Representations in Computer Animation: a Compared Study  

Microsoft Academic Search

How can Implicit Surfaces be used in the context of high-end Com- puter Animation ? This paper compares two different representa- tions of field functions - the constructive approach and the fi eld image approach. Their respective advantages and limitations for the definition of animation and morphing algorithms, and for the visualization of an animation are discussed. We show that

Marie-Paule Cani

1999-01-01

164

Insights into restrictive cardiomyopathy from clinical and animal studies  

PubMed Central

Cardiomyopathies are diseases that primarily affect the myocardium, leading to serious cardiac dysfunction and heart failure. Out of the three major categories of cardiomyopathies (hypertrophic, dilated and restrictive), restrictive cardiomyopathy (RCM) is less common and also the least studied. However, the prognosis for RCM is poor as some patients dying in their childhood. The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective. In this article, we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models. This will help for a better understanding of the mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.

Jean-Charles, Pierre-Yves; Li, Yue-Jin; Nan, Chang-Long; Huang, Xu-Pei

2011-01-01

165

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.

166

Regulatory Issues Surrounding the Use of Companion Animals in Clinical Investigations, Trials, and Studies  

Microsoft Academic Search

Laboratory animal veterinarians sometimes encounter ani- mals with rare conditions and may subsequently become involved in the performance of related animal research out- side the laboratory, in homes, in veterinary clinics, or in universities to which owners have donated their animals for study. Similarly, veterinarians may monitor animal compan- ion vaccination studies, performed to optimize preventive health care or minimize

Victoria A. Hampshire

2003-01-01

167

Microglial activation in a neuroinflammational animal model of schizophrenia--a pilot study.  

PubMed

Inflammatory and immunological processes interfering with brain development are discussed as one cause of schizophrenia. Various signs of overactivation of the immune system were often found in this disease. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, PolyI:C incubation of pregnant dams was used as animal model of schizophrenia, and the number and shape of microglia were assessed in the offspring in the early phase of this disease, using fluorescence immunostaining (Iba1). Descendants of mice exposed to PolyI:C at embryonic day 9 showed higher number of microglial cells in the hippocampus and striatum, but not in the frontal cortex at postnatal day 30, which is similarly to adolescence in man, as compared to those exposed to saline. Furthermore, offspring microglia from PolyI:C treated mothers were morphologically characterized by a reduced arborization indicative for a status of higher activation compared to the offspring microglia from vehicle treated mice. This study supports the hypothesis that maternal infection during embryogenesis contributes to microglial activation in the offspring, which may therefore represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options in this regard. PMID:21752601

Juckel, Georg; Manitz, Marie Pierre; Brüne, Martin; Friebe, Astrid; Heneka, Michael T; Wolf, Rainer J

2011-07-12

168

Epidemiological Study of Animal Leptospirosis in New Caledonia  

PubMed Central

Leptospirosis is an important zoonotic disease in the world and a real public health concern for many years in New Caledonia. A cross-sectional survey was carried out on domestic and wild animals from New Caledonia in April 2009. Blood samples were collected from 30 cattle, 29 deers, (Cervus timorensis russa), 25 horses, 51 dogs, and 8 cats and were tested for 23 serovars of pathogenic Leptospira species by the microscopic agglutination test. From the total number of 143 samples, 84 (58.7%) were found to be positive towards one or several serovars of pathogenic leptospires. According to the species, the positive sera were obtained from 43% of 30 cattle, 72% of 29 Rusa deer, 80% of 25 horses, and 43% of 51 dogs, and fromall of the 8 cats tested. This study shows the broad dispersion and the high prevalence of the different serogroups of pathogenic Leptospira species tested, particularly among deer and horses. The disease is endemic in domestic animals and concerns all the species.

Roqueplo, Cedric; Cabre, Olivier; Davoust, Bernard; Kodjo, Angeli

2013-01-01

169

Antioxidant vitamins in atherosclerosis--animal experiments and clinical studies.  

PubMed

Atherosclerotic heart diseases are universal problems in modern society. Oxidative damage to lipids is a primary cause of atherosclerosis. There are many choices for treatment, but no definite recommendations to prevent the occurrence of the disease. There is a relationship between atherosclerotic risk factors and increased vascular production of reactive oxygen species (ROS). Oxidized low-density lipoproteins (LDL) and ROS may directly cause endothelial dysfunction by reducing endothelial nitric oxide (NO) bioavailability. Vitamin E can to some degree prevent the consequences of oxidized LDL, and vitamin C provides NO synthase activity. Although prolonged use of vitamin A, C, and E supplementation in pharmaceutical forms has been proven to be effective in preventing atherosclerosis in animal experiments, this has not yet been demonstrated in clinical trials with human beings. It should be taken into account that the evidence has been gathered from young/adult experimental animals with early stages of arthrosclerosis and from in-vitro studies, while most of the clinical trials have involved older patients with late stages of the disease. Prolonged use of vitamins in the diet has not yet been recommended in human beings. There is some indication that a diet rich in antioxidant fruit and vegetables may be beneficial in the prevention of cardiovascular events. PMID:23214308

Ozkanlar, Seckin; Akcay, Fatih

170

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.

Holmes, Gregory L.; Zhao, Qian

2009-01-01

171

People's Study Time Allocation and its Relation to Animal Foraging  

PubMed Central

In this article we suggest a relation between people's metacognitively guided study time allocation strategies and animal foraging. These two domains are similar insofar as people use specific metacognitive cues to assist their study time allocation just as other species use cues, such as scent marking. People decline to study items that they know they already know, just as other species use a win-shift strategy – avoiding already visited and depleted patches – in foraging. People selectively study the easiest as-yet-unlearned items first, before turning to more difficult items just as other species take the ‘just right’ size and challenge of prey--the so-called Goldilocks principle. People use a stop rule by which they give up on one item and turn to another when the returns diminish just as others species use a stop rule that guides shifting from one patch to another. The value that each item is assigned on the criterion test, if known during study, influenced which items people choose to study and how long they study them just as knowledge of the nutritional or energy value of the food influences choices and perseverance in foraging. Finally, study time allocation strategies can differ in their effectiveness depending upon the expertise of the student just as some species forage close to optimally while others do not.

Metcalfe, Janet; Jacobs, W. Jake

2010-01-01

172

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.

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

173

Quantification of Cerebral Glucose Metabolic Rate in Mice Using 18F-FDG and Small-Animal PET  

Microsoft Academic Search

The aim of this study was to evaluate various methods for esti- mating the metabolic rate of glucose utilization in the mouse brain (cMRglc) using small-animal PET and reliable blood curves derived by a microfluidic blood sampler. Typical values of 18F- FDG rate constants of normal mouse cerebral cortex were esti- mated and used for cMRglc calculations. The feasibility of

Amy S. Yu; Hong-Dun Lin; Sung-Cheng Huang; Michael E. Phelps; Hsiao-Ming Wu

174

21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.  

Code of Federal Regulations, 2010 CFR

...based on evidence of effectiveness from studies in animals. 601.91 Section 601...Biological Products When Human Efficacy Studies Are Not Ethical or Feasible § 601...based on evidence of effectiveness from studies in animals. (a) FDA may...

2010-04-01

175

21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.  

Code of Federal Regulations, 2010 CFR

...based on evidence of effectiveness from studies in animals. 601.91 Section 601...Biological Products When Human Efficacy Studies Are Not Ethical or Feasible § 601...based on evidence of effectiveness from studies in animals. (a) FDA may...

2009-04-01

176

Animal models for the study of cancer-induced anorexia.  

PubMed

Walker carcinoma 256/B transplanted sc in CD-COBS rats induce a decrease of food intake when the tumor size is less than 5% of the body weight. This anorexia is accompanied by a decrease of the adipose tissue and, to a lesser extent, of muscular tissue. The mechanism involved in cancer-induced anorexia seems to be different from that of classic centrally acting anorectic agents. Among the drugs tested to counteract this anorexia only cyproheptadine shows a modest effect. Cyclophosphamide reduces tumor growth and prevents decrease in food intake. It is suggested that Walker carcinoma 256/B may be a useful animal model to study problems related to cancer-induced anorexia and cachexia. PMID:6955017

Garattini, S; Guaitani, A

1981-01-01

177

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

178

A search filter for increasing the retrieval of animal studies in Embase  

Microsoft Academic Search

Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal

R. B. M. de Vries; C. R. Hooijmans; A. Tillema; M. Leenaars; M. Ritskes-Hoitinga

2011-01-01

179

Creating animations using virtual reality ThatcherWorld: a case study  

Microsoft Academic Search

This paper describes the creation of a Western shootout animation for a BBC2 television production. This provides a case study describing the interaction between the TV production team and the animators. The animation was produced by explicitly programming transformations applied to nodes in hierarchical models of simple human characters. A subsequent project has attempted to provide character animation making use

Mel Slater; Martin Usoh; Razia Geeas; Anthony Steed

1995-01-01

180

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

181

Toward new understandings of human–animal relationships in sport: a study of Australian jumps racing  

Microsoft Academic Search

The importance of studying human–animal relationships and animal subjectivity is increasingly recognised by social and cultural geographers, particularly in agricultural pursuits. Little research, however, has been undertaken on animals in sport, resulting in a limited understanding of the perceptions and treatment of animals in society. To address this concern, we interrogate print media coverage of the construction and positioning of

Phil McManus; Daniel Montoya

2012-01-01

182

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

183

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

184

Telemetry in Biometeorological Studies, Telemetry in Animal Biometeorology.  

National Technical Information Service (NTIS)

The paper reviews the remarkable changes in the last 40-50 years in the way measurements are made in animal biometeorology. The experiments which were done to describe the adaptations which made the life of the animal possible, were accomplished with meas...

G. E. Folk J. R. Copping

1972-01-01

185

USC study finds fasting weakens cancer in mice  

Cancer.gov

Cancer in animals appears less resilient and chemotherapy drugs work better when combined with cycles of short, severe fasting, shows a University of Southern California study. Even fasting on its own effectively treated a majority of cancers tested in animals, including cancers from human cells.

186

Autobacteriographic studies of clarithromycin and erythromycin in mice  

SciTech Connect

The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with (N-methyl-14C)clarithromycin and (N-methyl-14C)erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for (14C)clarithromycin than it was for (14C)erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. (Taisho Pharmaceutical Co., Ltd., Ohmiya (Japan))

1990-04-01

187

Sponge implant in Swiss mice as a model for studying loxoscelism.  

PubMed

Envenomation by Loxosceles spider bite leads to a set of signs and symptoms, called loxoscelism, which in most cases manifests through the dermonecrotic frame. The development of a smaller size animal model, of easy handling and maintenance, and lower cost is needed to study the loxoscelism pathogenesis. The inflammatory effects of the Loxosceles similis crude venom was evaluated considering neutrophil and macrophage activation, vasodilatation, hyperhaemia, edema and hemorrhage and TNF-? and VEGF production using the murine sponge implant model. Thirty two male Swiss mice (6-8 weeks old) were implanted subcutaneously with polyether-polyurethane sponge discs. Fourteen days post implantation, animals were separated into two groups: (1) control group--16 mice received 30 ?L of saline intra-implant; (2) treated group-sixteen mice injected with 0.5 ?g/30 ?L of L. similis crude venom intra-implant. The animals were euthanized with xylazine/ketamine after 1 and 4 h post- injection. Microscopically, implants of the treated groups presented an acute inflammation characterized by: neutrophilic infiltrate, edema, vasodilatation hyperhaemia, and severe hemorrhage. Some vessels presented ruptured walls. Under morphometric analysis, vessel area was bigger in the treated groups compared with the control ones. The biochemical parameters, hemoglobin content, inflammatory enzyme activities (myeloperoxidase and n-acethyl-?-D glucosaminidase) and levels of the cytokines, TNF-? and VEGF, were also significantly higher in the venom-treated groups. The effects of Loxosceles venom in the granulation tissue of the implant in mice were similar to those observed in cutaneous loxoscelism in other species (human and rabbits). Consequently, the murine sponge implant model provides a new method to investigate cellular/molecular mechanisms associated with cutaneous loxoscelism. PMID:22406472

Pereira, Núbia Braga; Campos, Paula Peixoto; de Jesus Oviedo Socarrás, Teresa; Pimenta, Thaiane Salgado; Parreiras, Patrícia Martins; Silva, Soraia Silvéria; Kalapothakis, Evanguedes; Andrade, Silvia Passos; Moro, Luciana

2012-03-03

188

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.

Bozzella, Michael J.; Seluanov, Andrei

2008-01-01

189

Current Animal Models: Cotton Rat Animal Model  

Microsoft Academic Search

The cotton rat ( Sigmodon hispidus ) model has proven to be a suitable small animal model for measles virus pathogenesis to fill the niche between tissue culture\\u000a and studies in macaques. Similar to mice, inbred cotton rats are available in a microbiologically defined quality with an\\u000a ever-increasing arsenal of reagents and methods available for the study of infectious diseases.

S. Niewiesk

190

Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone disease  

Microsoft Academic Search

The aims were to optimize reproducibility and establish [18F]fluoride ion bone scanning in mice, using a dedicated small animal positron emission tomography (PET) scanner (microPET) and to correlate functional findings with anatomical imaging using computed tomography (microCAT). Optimal tracer uptake time for [18F]fluoride ion was determined by performing dynamic microPET scans. Quantitative reproducibility was measured using region of interest (ROI)-based

Frank Berger; Yu-Po Lee; Andreas M. Loening; Arion Chatziioannou; Stephen J. Freedland; Richard Leahy; Jay R. Lieberman; Arie S. Belldegrun; Charles L. Sawyers; Sanjiv S. Gambhir

2002-01-01

191

An animal model for human cellular immunotherapy: specific eradication of human acute lymphoblastic leukemia by cytotoxic T lymphocytes in NOD\\/scid mice  

Microsoft Academic Search

Adoptive immunotherapy using in vitro- generated donor-derived cytotoxic T lym- phocytes (CTLs) can be effective in the treatment of relapsed leukemia after allo- geneic transplantation. To determine ef- fector cell characteristics that result in optimal in vivo antileukemic efficacy, we developed an animal model for human CTL therapy. Nonobese diabetic\\/severe combined immunodeficiency (NOD\\/scid) mice were inoculated with either of 2

Bart A. Nijmeijer; Roel Willemze; J. H. Frederik Falkenburg

192

Ccl2\\/Cx3cr1Deficient Mice: An Animal Model for Age-Related Macular Degeneration  

Microsoft Academic Search

Background\\/Aims: Senescent Ccl2–\\/– mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD. Methods: We generated Ccl2–\\/–\\/Cx3cr1–\\/– [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics. Results: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells,

Chi-Chao Chan; Robert J. Ross; Defen Shen; Xiaoyan Ding; Zigurts Majumdar; Christine M. Bojanowski; Min Zhou; Robert Bonner; Jingsheng Tuo

2008-01-01

193

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

194

Alzheimer's disease biomarkers: correspondence between human studies and animal models.  

PubMed

Alzheimer's disease (AD) represents an escalating global threat as life expectancy and disease prevalence continue to increase. There is a considerable need for earlier diagnoses to improve clinical outcomes. Fluid biomarkers measured from cerebrospinal fluid (CSF) and blood, or imaging biomarkers have considerable potential to assist in the diagnosis and management of AD. An additional important utility of biomarkers is in novel therapeutic development and clinical trials to assess efficacy and side effects of therapeutic interventions. Because many biomarkers are initially examined in animal models, the extent to which markers translate from animals to humans is an important issue. The current review highlights many existing and pipeline biomarker approaches, focusing on the degree of correspondence between AD patients and animal models. The review also highlights the need for greater translational correspondence between human and animal biomarkers. PMID:23631871

Sabbagh, Jonathan J; Kinney, Jefferson W; Cummings, Jeffrey L

2013-04-28

195

[Lymphocyte migration in internally irradiated animals. Effect of internal beta radiation on the migration of spleen lymphocytes in CBA mice].  

PubMed

The syngeneic transfer system was used to study migration of 51Cr-labelled spleen lymphocytes in mice after incorporation of beta-emitter, 35S-methionine. Migration of 51Cr-labelled lymphocytes to lymph nodes was stably decreased, and to liver, kidneys and lungs increased. The lymphocyte migration impairment was associated with the influence of beta-radiation on both the migratory properties of cells and the factors of their microenvironment responsible for the lymphocyte migration within the mouse body. No distinctions were observed in the character and manifestation of disturbances of the lymphocyte migration after the injection of 35S-methionine and gamma-emitter, 75Se-selenomethionine. PMID:6611875

Anokhin, Iu N; Norets, T A; Iarilin, A A; Stepanenko, V F

196

In utero exposure to valproic acid and autism--a current review of clinical and animal studies.  

PubMed

Valproic acid (VPA) is both an anti-convulsant and a mood stabilizer. Clinical studies over the past 40 years have shown that exposure to VPA in utero is associated with birth defects, cognitive deficits, and increased risk of autism. Two recent FDA warnings related to use of VPA in pregnancy emphasize the need to reevaluate its use clinically during child-bearing years. The emerging clinical evidence showing a link between VPA exposure and both cognitive function and risk of autism brings to the forefront the importance of understanding how VPA exposure influences neurodevelopment. In the past 10 years, animal studies have investigated anatomical, behavioral, molecular, and physiological outcomes related to in utero VPA exposure. Behavioral studies show that VPA exposure in both rats and mice leads to autistic-like behaviors in the offspring, including social behavior deficits, increased repetitive behaviors, and deficits in communication. Based on this work VPA maternal challenge in rodents has been proposed as an animal model to study autism. This model has both face and construct validity; however, like all animal models there are limitations to its translation to the clinical setting. Here we provide a review of clinical studies that examined pregnancy outcomes of VPA use as well as the related animal studies. PMID:23395807

Roullet, Florence I; Lai, Jonathan K Y; Foster, Jane A

2013-02-08

197

Studies on colchicine, colchicine derivatives, and endotoxin in irradiated animals  

Microsoft Academic Search

Colchicine when given 3, 2, or 1 day and trimethylcolchicinic acid ; methyl ether, colchiceinamide, colchiceine, and N-acetylcolchinol when given 1 ; day before irradiation caused an increase in survival of mice, provided they were ; more than 7 weeks old and the radiation dose one which causes death in ; approximately 1 to 4 weeks. Colchicine administration did not

W. W. Smith; I. M. Alderman

1962-01-01

198

Animal welfare and use of silkworm as a model animal.  

PubMed

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare. PMID:23006994

Sekimizu, N; Paudel, A; Hamamoto, H

2012-08-01

199

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

2013-02-06

200

Human Malaria in Immunocompromised Mice: New In Vivo Model for Chemotherapy Studies  

PubMed Central

We have recently designed a new Plasmodium falciparum mouse model and documented its potential for the study of immune effector mechanisms. In order to determine its value for drug studies, we evaluated its response to existing antimalarial drugs compared to that observed in humans. Immunocompromised BXN (bg/bg xid/xid nu/nu) mice were infected with either the sensitive NF54 strain or the multiresistant T24 strain and then treated with chloroquine, quinine, mefloquine, or dihydroartemisinin. A parallelism was observed between previously reported human responses and P. falciparum-parasitized human red blood cell (huRBC)–BXN mouse responses to classical antimalarial drugs, measured in terms of speed of decrease in parasitemia and of morphological alterations of the parasites. Mice infected with the sensitive strain were successfully cured after treatment with either chloroquine or mefloquine. In contrast, mice infected with the multiresistant strain failed to be cured by chloroquine or quinine but thereafter responded to dihydroartemisinin treatment. The speed of parasite clearance and the morphological alterations induced differed for each drug and matched previously reported observations, hence stressing the relevance of the model. These data thus suggest that P. falciparum-huRBC–BXN mice can provide a valuable in vivo system and should be included in the short list of animals that can be used for the evaluation of P. falciparum responses to drugs.

Moreno, A.; Badell, E.; Van Rooijen, N.; Druilhe, P.

2001-01-01

201

Developmental Effects of SSRI's - Lessons learned from Animal Studies  

PubMed Central

Selective serotonin reuptake inhibitors (SSRI’s) are utilized in the treatment of depression in pregrant and lactating women. SSRI’s may be passed to the fetus through the placenta and the neonate through breastfeeding, potentially exposing them to SSRIs during peri and postnatal development. However, the long-term effects of this SSRI exposure are still largely unknown. The simplicity and genetic amenability of model organisms is a significant advantage to work with humans. This review will assess the current research done in animals that sheds light on the role of serotonin during development and the possible effects of SSRIs. Experimental studies in rodents show that administration of SSRIs during a key developmental window creates changes in brain circuitry and maladaptive behaviors that persist into adulthood. Similar changes result from the inhibition of serotonin transporter or monoamine oxidase, implicating these two regulators of serotonin signaling in developmental changes. Understanding the role of serotonin in brain development is critical to identifying the possible effects of SSRI exposure.

Borue, Xenia; Chen, John; Condron, Barry G.

2007-01-01

202

Carcinogenesis studies of benzophenone in rats and mice  

PubMed Central

Benzophenone, an aryl ketone, is used primarily as a photoinitiator and fragrance enhancer. Groups of 50 male and 50 female F344 rats and B6C3 F1 mice were fed diets containing 0, 312, 625, and 1, 250 ppm benzophenone for 105 weeks. Survival of males exposed to 1, 250 ppm benzophenone was significantly less than that of controls. There was a positive trend in the incidence of renal tubule adenoma in male rats; these neoplasms were accompanied by significantly increased incidences of renal tubule hyperplasia. Increased incidences of mononuclear cell leukemia were observed in male rats exposed to 312 or 625 ppm benzophenone and in female rats exposed to 625 ppm benzophenone. Liver lesions observed included significantly increased incidences of hepatocytic centrilobular hypertrophy in all exposed groups of rats. In mice, survival of all exposed groups was generally similar to that of the control groups. In male mice, there were significantly increased incidences of hepatocellular adenoma in the 625 and 1, 250 ppm groups. In female mice, the incidences of hepatocellular adenoma in the 625 and 1,250 ppm groups were higher than expected after adjusting for the lower body weights in these groups. The incidences of kidney nephropathy in exposed groups of female mice, as well as the severity of nephropathy in exposed groups of males, were significantly increased. The incidences of metaplasia of the olfactory epithelium were significantly increased in 1, 250 ppm mice. Rare histiocytic sarcomas were observed in female rats and mice in the 625 and 1,250 ppm groups. Under the conditions of these 2-year studies, there was some evidence of carcinogenic activity of benzophenone in male F344/N rats based on increased incidences of renal tubule adenoma. There was equivocal evidence of carcinogenic activity of benzophenone in female F344/N rats based on the marginal increased incidences of mononuclear cell leukemia and histiocytic sarcoma. There was some evidence of carcinogenic activity of benzophenone in male B6C3F1 mice based on increased incidences of hepatocellular neoplasms, primarily adenoma. There was some evidence of carcinogenic activity of benzophenone in female B6C3F1 mice based on increased incidences of histiocytic sarcoma; the incidences of hepatocellular adenoma in female B6C3F1 mice may have been related to benzophenone exposure.

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

2007-01-01

203

Immunohistochemical studies of basal cell carcinomas transplanted into nude mice  

Microsoft Academic Search

Xenografting into nude mice forms a system for analysis of human tissues under experimental conditions. In this study, normal skin samples and basal cell carcinomas were investigated, prior to and after transplantation, using immunofluorescence methods with antibodies against keratins, laminin, and collagen type IV. Three groups of transplants were studied: (a) intact tissue samples, (b) human epithelium (either normal or

T. H. Löning; I. C. Mackenzie

1986-01-01

204

[11C]sorafenib: radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice.  

PubMed

Sorafenib (Nexavar, BAY43-9006, 1) is a second-generation, orally active multikinase inhibitor that is approved for the treatment of some cancers in patients. In this Letter, we developed [(11)C]1 as a novel positron emission tomography (PET) probe, and evaluated the influence of ABC transporters-mediated efflux on brain uptake using PET with [(11)C]1 in P-glycoprotein (P-gp)/breast cancer resistance protein (Bcrp) knockout mice versus wild-type mice. [(11)C]1 was synthesized by the reaction of hydrochloride of aniline 2 with [(11)C]phosgene ([(11)C]COCl(2)) to give isocyanate [(11)C]6, followed by reaction with another aniline 3. Small-animal PET study with [(11)C]1 indicated that the radioactivity level (AUC(0-60 min), SUV×min) in the brains of P-gp/Bcrp knockout mice was about three times higher than in wild-type mice. PMID:21419625

Asakawa, Chiharu; Ogawa, Masanao; Kumata, Katsushi; Fujinaga, Masayuki; Kato, Koichi; Yamasaki, Tomoteru; Yui, Joji; Kawamura, Kazunori; Hatori, Akiko; Fukumura, Toshimitsu; Zhang, Ming-Rong

2011-03-06

205

Multi-Chamber System for Toxicity Studies in Mice at Simulated High Altitude.  

National Technical Information Service (NTIS)

Plastic desiccators have been adapted to serve as chambers in a simulated high altitude system. The multi-chambered system is convenient for observations of grouped mice or other small animals subjected to decompression. Toxicity data are given for repres...

I. P. Baumel S. M. Robinson W. F. Blatt

1967-01-01

206

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

207

Choosing an animal model for the study of Huntington's disease.  

PubMed

Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD. PMID:24052178

Pouladi, Mahmoud A; Morton, A Jennifer; Hayden, Michael R

2013-10-01

208

Methyl isocyanate: reproductive and development toxicology studies in Swiss mice  

SciTech Connect

Studies were conducted in Swiss (CD-1) mice to evaluate the potential of inhaled vapors of methyl isocyanate (MIC) to affect reproduction and development. Inhaled MIC at concentrations of 0, 1, or 3 ppm, 6 hr per day during days 14 through 17 of gestation caused a significant increase in the number of dead fetuses at birth and caused a significant decrease in neonatal survival during lactation. In contrast, exposure of male and female mice to 1 or 3 ppm given 6 hr per day for 4 consecutive days had no effect on reproduction during mating trials conducted 1, 8, and 17 weeks after the exposure period. Similarly, there was no evidence of a dominant lethal effect in exposed male mice.

Schwetz, B.A.; Adkins, B. Jr.; Harris, M.; Moorman, M.; Sloane, R.

1987-06-01

209

Subchronic toxicity study in mice fed Spirulina maxima  

Microsoft Academic Search

The purpose of this study was to evaluate the toxicity of Spirulina maxima, a blue–green alga used as food supplement and food coloring, after 13 weeks of treatment. Groups of ten mice of each sex were given S. maxima in the diet at concentrations of 0 (control), 10, 20 or 30% (w\\/w) for 13 weeks. The alga ingestion had no

M Salazar; E Mart??nez; E Madrigal; L. E Ruiz; G. A Chamorro

1998-01-01

210

The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice.  

PubMed

The use of the aged mouse as an integrated model of age-related cognitive decline is reviewed, with special emphasis on experiments covering the life span of NMRI mice, using different age-groups ranging from 3 through to 22 months. Age-related changes in the sensorimotor profile, spontaneous behaviour and performance in learning and memory tasks are considered. The data provide evidence for cognitive impairment and decreases in spontaneous activity and exploration from middle age onwards. Chronologically, this age depends on the longevity of the strain selected; in NMRI mice, middle age corresponds to 11-12 months. Complex learning tasks, such as the Morris water maze for spatial learning, appear to be the most sensitive to age-related changes, as are tests requiring prolonged retention of acquired information, for example, using passive avoidance. Cued and simple discrimination learning are only impaired in the oldest animals. Age-related changes in non-cognitive variables, including sensorimotor capacity, pain sensitivity, emotionality, or locomotor activity, do not account for the learning impairments, although deficits in visual acuity cannot be excluded in the very old animals. Detailed analysis of the individual data for middle aged and old mice, using discriminant and correlation studies highlight a marked heterogeneity between animals of any given chronological age. Furthermore, individual aged mice do not exhibit similar degrees of impairment across all the behavioural variables, showing that aging is not a uniform process. The possible relationship between age-related behavioural decline and neurochemical changes is an area as yet unexplored apart from a few isolated investigations, including a study on ChAT and AChE in NMRI mice. The studies in the NMRI mice illustrate the value of investigating the full age-range to detect an age group which shows cognitive decline dissociable from physical or emotional changes and which is representative of the population as a whole. PMID:8117421

Gower, A J; Lamberty, Y

1993-11-30

211

A Comparative Study of Skeletal and Keyframe Animations in a Multiplayer Online Game  

Microsoft Academic Search

As the game development process is a very tedious one, a good knowledge of which game animation technique that work best in practice is very essential. In this paper we study the performance of two popular animation models - the skeletal and key frame animation models. We have done some experiments using a test bed program to measure the performance,

Garry Pranatio; Raymondus Kosala

2010-01-01

212

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 envi- ronmental research. Recently, animal physiological ecologists have also applied stable isotope techniques to study plant- animal relationships. The isotopic compositions of animal body generally reflect and integrate their diets over a time period ranging from hours to years to the lifetime of an indi- vidual.

Jianzhu WANG; Guanghui Lin; Jianhui Huang; Xingguo Han

2004-01-01

213

Morphological and immunohistochemical studies of the central nervous system involvement in papovavirus K infection in mice  

Microsoft Academic Search

The murine papovavirus K causes fatal pneumonia in infant mice, but an asymptomatic infection in older mice. In order to establish whether the virus affects the central nervous system in the course of systemic infection, we carried out morphological and immunohistochemical studies on the experimentally infected mice. BALB\\/c mice, less than 4 days of age, were inoculated with K virus

K. Ikeda; K. Dörries; V. Meulen

1988-01-01

214

Invasive and noninvasive methods for studying pulmonary function in mice  

PubMed Central

The widespread use of genetically altered mouse models of experimental asthma has stimulated the development of lung function techniques in vivo to characterize the functional results of genetic manipulations. Here, we describe various classical and recent methods of measuring airway responsiveness in vivo including both invasive methodologies in anesthetized, intubated mice (repetitive/non-repetitive assessment of pulmonary resistance (RL) and dynamic compliance (Cdyn); measurement of low-frequency forced oscillations (LFOT)) and noninvasive technologies in conscious animals (head-out body plethysmography; barometric whole-body plethysmography). Outlined are the technical principles, validation and applications as well as the strengths and weaknesses of each methodology. Reviewed is the current set of invasive and noninvasive methods of measuring murine pulmonary function, with particular emphasis on practical considerations that should be considered when applying them for phenotyping in the laboratory mouse.

Glaab, Thomas; Taube, Christian; Braun, Armin; Mitzner, Wayne

2007-01-01

215

Rescue of mice homozygous for lethal albino deletions: implications for an animal model for the human liver disease tyrosinemia type 1.  

PubMed

Mice homozygous for specific deletions around the albino locus on chromosome 7 die within the first few hours of birth. They have a complex phenotype in liver and kidney, which includes multiple changes in gene expression and ultrastructural abnormalities. On the basis of this phenotype, it was proposed that these deletions remove a regulatory locus, alf or hsdr-1. Recently, we and others showed that the gene for fumarylacetoacetate hydrolase (Fah), an enzyme involved in tyrosine catabolism, was disrupted by the lethal albino deletion c14CoS. The finding that the Fah gene in wild-type mice is highly expressed only in cell types that develop a phenotype in mutants, and the fact that Fah deficiency determines the human liver disease hereditary tyrosinemia type 1 (HT1), suggested that disruption of the Fah gene was responsible for the lethal albino phenotype. To test this hypothesis, we have created lines of mice carrying Fah transgenes. We find that c14CoS homozygotes which express transgenic Fah are complemented for all aspects of the complex lethal albino phenotype. Moreover, the degree to which the phenotype is corrected depends on the level of transgenic Fah expression. These results unequivocally establish Fah as the gene mapping at alf/hsdr-1 and prove that the phenotype depends ultimately on the blockage of tyrosine metabolism. Finally, they suggest lethal albino mice as an animal model for HT1. PMID:8253377

Kelsey, G; Ruppert, S; Beermann, F; Grund, C; Tanguay, R M; Schütz, G

1993-12-01

216

Infantile stimulation and animal husbandry: A methodological study  

Microsoft Academic Search

Effects of 2 animal husbandry conditions during infancy––the method of presenting food to the mother and the changing or not changing of shavings––in combination with handling during infancy were investigated in rats. Dependent variables were body weight and open-field behavior. Handled Ss weighed significantly more in adulthood and were significantly more active in the open field. Ss whose shavings were

Victor H. Denenberg; Arthur E. Whimbey

1963-01-01

217

Recombinant immunotoxins with low endotoxins for clinical and animal studies.  

PubMed

Recombinant immunotoxin (RIT) contains the Fv portion of the antibody fused to the truncated form of toxin and are ongoing in clinical trials for cancer therapy. To obtain high yields of products, RITs are produced in Escherichia coli (E. coli). As the endotoxin came from E. coli cells and is harmful to animals, it is important to produce the RITs with low endotoxin. This section describes the protocols to produce RITs containing low level of endotoxins. PMID:22907377

Onda, Masanori

2012-01-01

218

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.

Giardina, Irene

2008-01-01

219

Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.  

PubMed

Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid ?-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid ?-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid ?-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid ?-glucosidase and the common mutations underlying Gaucher disease. PMID:23642305

Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

2013-04-30

220

A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain  

PubMed Central

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons ?, ?, and ? (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker Multi-Analyte Profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals.

Thibodeaux, Brett A.; Garbino, Nina C.; Liss, Nathan M.; Piper, Joseph; Blair, Carol D.; Roehrig, John T.

2012-01-01

221

A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.  

PubMed

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons ?, ?, and ? (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker multi-analyte profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals. PMID:22425792

Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Blair, Carol D; Roehrig, John T

2012-03-13

222

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

223

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

224

Validation Studies on Blood Collection from the Jugular Vein of Conscious Mice  

PubMed Central

A method for blood collection from the jugular vein of mice without anesthesia was compared with a tail-incision technique. Jugular vein blood collection allowed withdrawal of almost 15% of the circulating blood volume at a time in less than 1 min. Hemolysis, hematocrit, and plasma thrombin–antithrombin complexes (a marker of blood coagulation) were higher in samples collected from the tail vein than the jugular vein. Mice produced similar plasma corticosterone levels after serial blood collection by either method. Tail incision led to a slight but significant increase in C-reactive protein levels. Using the jugular venipuncture technique, we then performed a pharmacokinetic study and an oral glucose tolerance test. Plasma concentrations of levofloxacin, an antimicrobial agent, were dose-dependently elevated after oral administration, and linear increases in Cmax and AUC were observed. We also confirmed that overall glucose excursion is significantly decreased in mice treated with exendin 4, a glucagon-like peptide 1 agonist. These results indicate that the jugular venipuncture is a useful technique from the point of view of no requirement for anesthetics, serial blood collection at short intervals, large volume of blood collection, quality of sample and animal welfare. This technique is of particular interest for studies that examine time-dependent changes in blood variables.

Shirasaki, Yasufumi; Ito, Yoshihiro; Kikuchi, Miho; Imamura, Yuichiro; Hayashi, Toshiaki

2012-01-01

225

Studies on the Influence of Laser Beams on Wound Granulation. An Animal Study.  

National Technical Information Service (NTIS)

The influence of laser light of low energy on wound healing was tested on 204 rats in a blind study. The growth of granulation tissue in a polyvinylchloride cylinder implanted on the backs of the animals served as parameter for wound healing. Irradiation ...

R. Brunner

1982-01-01

226

Toward an Understanding of Human Violence: Cultural Studies, Animal Studies, and the Promise of Posthumanism  

ERIC Educational Resources Information Center

|On January 3, 2012, the "New York Times" featured an article announcing the emergence of the new interdisciplinary field of animal studies, which is spreading across college campuses in new course offerings, new majors, and new undergraduate and graduate programs. This new field grows out of, on the one hand, a long history of scientific research…

Worsham, Lynn

2013-01-01

227

Of mice and men: what animal research can tell us about context effects on automatic responses in humans.  

PubMed

Automatic responses play a central role in many areas of psychology. Counter to views that such responses are relatively rigid and inflexible, a large body of research has shown that they are highly context-sensitive. Research on animal learning and animal behavior has a strong potential to provide a deeper understanding of such context effects by revealing remarkable parallels between the functional properties of automatic responses in human and nonhuman animals. These parallels involve the contextual modulation of attitude formation and change (automatic evaluation), and the role of contextual contingencies in shaping the particular action tendencies in response to a stimulus (automatic behavior). Theoretical concepts of animal research not only provide novel insights into the processes and representations underlying context effects on automatic responses in humans; they also offer new perspectives on the interface between affect, cognition, and motivation. PMID:23470281

Gawronski, Bertram; Cesario, Joseph

2013-03-06

228

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.  

Code of Federal Regulations, 2010 CFR

...based on evidence of effectiveness from studies in animals. 314.610 Section 314...Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314...based on evidence of effectiveness from studies in animals. (a) FDA may...

2010-04-01

229

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.  

Code of Federal Regulations, 2010 CFR

...DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or...results of those animal studies establish that the drug product is reasonably...studies, such as field studies, to verify and describe the drug's clinical...

2009-04-01

230

Further metabolic studies of codeine and morphine in mice pretreated with sympathomimetics.  

PubMed

The effects of ephedrine and phenylpropanolamine (PPA) on the 24 h urinary excretion of morphine, codeine and their metabolites, and on the plasma and brain disposition of morphine and codeine at steady state in mice were studied. Morphine-3-glucuronide was the major urinary metabolite in morphine treated animals, while for codeine treated animals norcodeine and morphine-3-glucuronide were the major metabolites. In all cases percentage of drug excreted unchanged was 10-15% of the administered dose. Ephedrine or PPA pretreatment had no apparent effect on these parameters. The metabolic ratios for the different pathways were comparable in all treatment groups. Steady-state plasma and brain concentration-time profiles of codeine and morphine also showed marked similarity in all treatment groups. Apparently, ephedrine or PPA pretreatment has no effect on the disposition of morphine and codeine in mice. The results are discussed from the perspective of our earlier findings of dependence on cough mixtures containing opioids and sympathomimetics. PMID:1297894

Dambisya, Y M; Chan, K; Wong, C L

1992-12-01

231

Family of Enhanced Photoacoustic Imaging Agents for High Sensitivity and Multiplexing Studies in Living Mice  

PubMed Central

Photoacoustic imaging is a unique modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a family of novel photoacoustic contrast agents that are based on the binding of small optical dyes to single walled carbon nanotubes (SWNT-dye). We synthesized five different SWNT-dye contrast agents using different optical dyes, creating five “flavors” of SWNT-dye nanoparticles. In particular, SWNT that were coated with either QSY21 (SWNT-QSY) or Indocyanine Green (SWNT-ICG) exhibited over 100-times higher photoacoustic contrast in living animals compared to plain SWNTs, leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the ?v?3 integrin, which is associated with tumor angiogenesis. Intravenous administration of these tumor-targeted imaging agents to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. Finally, we were able to spectrally separate the photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected subcutaneously with both particles in the same location, opening the possibility for multiplexing in vivo studies.

de Zerda, Adam; Bodapati, Sunil; Teed, Robert; May, Salomon Y.; Tabakman, Scott M.; Liu, Zhuang; Khuri-Yakub, Butrus T.; Chen, Xiaoyuan; Dai, Hongjie; Gambhir, Sanjiv S.

2012-01-01

232

Animal models for the study of influenza pathogenesis and therapy  

PubMed Central

Influenza A viruses causes a variety of illnesses in humans. The most common infection, seasonal influenza, is usually a mild, self-limited febrile syndrome, but it can be more severe in infants, the elderly, and immunodeficient persons, in whom it can progress to severe viral pneumonitis or be complicated by bacterial superinfection, leading to pneumonia and sepsis. Seasonal influenza also occasionally results in neurologic complications. Rarely, viruses that have spread from wild birds to domestic poultry can infect humans; such “avian influenza” can range in severity from mild conjunctivitis through the rapidly lethal disease seen in persons infected with the H5N1 virus that first emerged in Hong Kong in 1997. To develop effective therapies for this wide range of diseases, it is essential to have laboratory animal models that replicate the major features of illness in humans. This review describes models currently in use for elucidating influenza pathogenesis and evaluating new therapeutic agents.

Barnard, Dale L.

2009-01-01

233

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

234

Alterations in the expression of the Atp7a gene in the early postnatal development of the mosaic mutant mice (Atp7a mo-ms) - An animal model for Menkes disease.  

PubMed

Copper is a trace element that is essential for the normal growth and development of all living organisms. In mammals, the ATP7A Cu-transporting ATPase is a key protein that is required for the maintenance of copper homeostasis. In both humans and mice, the ATP7A protein is coded by the X-linked ATP7A/Atp7a gene. Disturbances in copper metabolism caused by mutations in the ATP7A/Atp7a gene lead to severe metabolic syndromes Menkes disease in humans and the lethal mottled phenotype in mice. Mosaic is one of numerous mottled mutations and may serve as a model for a severe Menkes disease variant. In Menkes patients, mutations in the ATP7A gene often result in a decreased level of the normal ATP7A protein. The aim of this study was to analyse the expression of the Atp7a gene in mosaic mutants in early postnatal development, a critical period for starting copper supplementation therapy in both Menkes patients and mutant mice. Using real-time quantitative RT-PCR, we analysed the expression of the Atp7a gene in the brain, kidney and liver of newborn (P0.5) and suckling (P14) mice. Our results indicate that in mosaic P0.5 mutants, the Atp7a mRNA level is decreased in all analysed organs in comparison with wild-type animals. In two week-old mutants, a significant decrease was observed only in the kidney. In contrast, their hepatic level of Atp7a tended to be higher than in wild-type mice. We speculate that disturbance in the expression of the Atp7a gene and, consequently, change in the copper concentration of the organs, may contribute to the early fatal outcome of mosaic males. PMID:20831904

Lenartowicz, Ma?gorzata; Starzy?ski, Rafa?; Wieczerzak, Krzysztof; Krzeptowski, Wojciech; Lipi?ski, Pawe?; Styrna, Józefa

2010-09-08

235

A search filter for increasing the retrieval of animal studies in Embase  

PubMed Central

Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments.

de Vries, Rob B M; Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

2011-01-01

236

A search filter for increasing the retrieval of animal studies in Embase.  

PubMed

Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments. PMID:21890653

de Vries, Rob B M; Hooijmans, Carlijn R; Tillema, Alice; Leenaars, Marlies; Ritskes-Hoitinga, Merel

2011-09-02

237

Behavioral studies with mice exposed to DC and 60-Hz magnetic fields  

SciTech Connect

Behavioral measures were evaluated in adult CD-1 and LAF-1 mice continuously exposed for 72 h to a 1.5-Tesla (1 T = 10/sup 4/ Gauss) homogeneous DC magnetic field, and in LAF-1 mice continuously exposed for 72 h to a sinusoidal 60-Hz, 1.65-mT (rms) homogeneous AC field. Three types of behavioral tests were employed: (1) memory of an electroshock-motivated passive avoidance task was assessed in animals that had been trained immediately prior to the field exposure. The strength of memory was varied either by altering the strength of the electric footshock during training, or by administering a cerebral protein synthesis inhibitor, anisomycin, at the time of training. (2) General locomotor activity was measured using a quadrant-crossing test immediately after termination of the magnetic field exposure. (3) Sensitivity of the experimental subjects to the seizure-inducing neuropharmacological agent, pentylenetetrazole, was assessed immediately after the field exposure on the basis of three criteria: (a) the percentage of subjects exhibiting a generalized seizure, (b) the mean time to seizure, and (c) the mean seizure level. The results of these studies revealed no behavior alterations in exposed mice relative to controls in any of the experimental tests with the 1.5-T DC field or the 60-Hz, 1.65-mT (rms) AC field. 57 references, 6 figures, 1 table.

Davis, H.P.; Mizumori, S.J.Y.; Allen, H.; Rosenzweig, M.R.; Bennett, E.L.; Tenforde, T.S.

1984-01-01

238

Dominant lethal mutations of topoisomerase II inhibitors etoposide and merbarone in male mice: a mechanistic study.  

PubMed

Two topoisomerase II inhibitors, etoposide and merbarone, were tested for the induction of dominant lethal mutations in male mice. Etoposide was administered at a dosage of 30 or 60 mg/kg. Merbarone was administered at a dosage of 40 or 80 mg/kg. These males were mated at weekly intervals to virgin females for 6 weeks. In the present experiments, regardless of the agent, spermatids appeared to be the most sensitive germ-cell stage to dominant lethal induction. Etoposide and merbarone clearly induced dominant lethal mutations in the early spermatid stage only with the highest tested doses. The mutagenic effects were also directly correlated with reactive oxygen species accumulation as an obvious increase in 2',7'-dichlorofluorescein fluorescence level was noted in the sperm of animals treated with higher doses of etoposide and merbarone. Treatment of male mice with N-acetylcysteine significantly protected mice from etoposide- and merbarone-induced dominant lethality. Moreover, N-acetylcysteine treatment had no antagonizing effect on etoposide- and merbarone-induced topoisomerase II inhibition. Overall, this study provides for the first time that etoposide and merbarone induce dominant lethal mutations in the early spermatid stage through a mechanism that involves increases in oxidative stress. The demonstrated mutagenicity profile of etoposide and merbarone may support further development of effective chemotherapy with less mutagenicity. PMID:22207148

Attia, Sabry M

2011-12-30

239

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

SciTech Connect

Starting in the early 1940s, Egon Lorenz and collaborators at the National Cancer Institute began an extended study of chronic low-level ionizing radiation effects in what was then the tolerance range for man. Observations on life span, body weight and radiation carcinogenesis, among others, were made in mice, guinea pigs and rabbits. At the then-permissible exposure level, 0.1 R** per 8-h day until natural death, experimental mice and guinea pigs had a slightly greater mean life span compared to control animals. In addition, there was marked weight gain during the growth phase in both species. Increased tumor incidence was also observed at the 0.1-R level in mice. The primary hypothesis for increased median life span has been rebound regenerative hyperplasia during the early part of the exposure; in the presence of continuing injury, there is physiological enhancement of defense mechanisms against intercurrent infection. The body weight gain has not been explained. 32 references.

Congdon, C.C.

1987-05-01

240

Inhibiting the Na+/H+ exchanger reduces reperfusion injury: a small animal MRI study.  

PubMed

We used magnetic resonance imaging (MRI) to assess the efficacy of Na+/H+ exchanger isoform 1 (NHE-1) inhibition following cerebral ischemia. Transient focal cerebral ischemia was induced in wild-type controls (NHE-1(+/+)), NHE-1 genetic knockdown mice (NHE-1(+/-)), and NHE-1(+/+) mice treated with the selective NHE-1 inhibitor HOE642. Diffusion weighted imaging (DWI) revealed a brain lesion as early as 1 hour following reperfusion and illustrated significant protection in NHE-1(+/-) mice (16.2 +/- 7.9 mm3 in NHE-1(+/-) mice vs. 47.5 +/- 16.6 mm3 in NHE-1(+/+) mice). Knockdown of NHE-1 showed significantly smaller infarct at 72 hours on T2 imaging (21.2 +/- 12.6 mm3 in NHE-1(+/-) mice vs. 64.6 +/- 2.5 mm3 in NHE-1(+/+) mice). Administration of HOE642 prior to reperfusion or during early reperfusion reduced ischemic damage. Thus, high resolution T2 images can be used for consistent and precise calculation of lesion volumes, while changes of DWI are a sensitive early marker of ischemic injury. The results of this study demonstrate the therapeutic potential for inhibition of NHE-1 in treating cerebral ischemia. PMID:21196287

Ferrazzano, Peter; Shi, Yejie; Manhas, Namratta; Wang, Yanping; Hutchinson, Beth; Chen, Xinzhi; Chanana, Vishal; Gerdts, Josiah; Meyerand, Mary Elizabeth; Sun, Dandan

2011-01-01

241

Inhibiting the Na+/H+ exchanger reduces reperfusion injury: a small animal MRI study  

PubMed Central

We used magnetic resonance imaging (MRI) to assess the efficacy of Na+/H+ exchanger isoform 1 (NHE-1) inhibition following cerebral ischemia. Transient focal cerebral ischemia was induced in wild-type controls (NHE-1+/+), NHE-1 genetic knockdown mice (NHE-1+/?), and NHE-1+/+ mice treated with the selective NHE-1 inhibitor HOE642. Diffusion weighted imaging (DWI) revealed a brain lesion as early as 1 hour following reperfusion and illustrated significant protection in NHE-1+/? mice (16.2 +/? 7.9 mm3 in NHE-1+/? mice vs. 47.5 +/? 16.6 mm3 in NHE-1+/+ mice). Knockdown of NHE-1 showed significantly smaller infarct at 72 hours on T2 imaging (21.2 +/? 12.6 mm3 in NHE-1+/? mice vs. 64.6 +/? 2.5 mm3 in NHE-1+/+ mice). Administration of HOE642 prior to reperfusion or during early reperfusion reduced ischemic damage. Thus, high resolution T2 images can be used for consistent and precise calculation of lesion volumes, while changes of DWI are a sensitive early marker of ischemic injury. The results of this study demonstrate the therapeutic potential for inhibition of NHE-1 in treating cerebral ischemia.

Ferrazzano, Peter; Shi, Yejie; Manhas, Namratta; Wang, Yanping; Hutchinson, Beth; Chen, Xinzhi; Chanana, Vishal; Gerdts, Josiah; Meyerand, Mary Elizabeth; Sun, Dandan

2010-01-01

242

Current animal models: cotton rat animal model.  

PubMed

The cotton rat (Sigmodon hispidus) model has proven to be a suitable small animal model for measles virus pathogenesis to fill the niche between tissue culture and studies in macaques. Similar to mice, inbred cotton rats are available in a microbiologically defined quality with an ever-increasing arsenal of reagents and methods available for the study of infectious diseases. Cotton rats replicate measles virus in the respiratory tract and (depending on virus strain) in lymphoid organs. They can be infected with vaccine, wild-type, and recombinant measles viruses and have been used to study viruses with genetic modifications. Other areas of study include efficacy testing of antivirals and vaccines. The cotton rat also has been an informative animal model to investigate measles virus-induced immune suppression and suppression of vaccination by maternal antibodies. In addition, the cotton rat promises to be a useful model for the study of polymicrobial disease (interaction between measles virus and secondary pathogens). PMID:19203106

Niewiesk, S

2009-01-01

243

Animal models for human Metapneumovirus (HMPV) infections  

Microsoft Academic Search

Since its detection in 2001 the human Metapneumovirus (HMPV), a member of the Paramyxoviridae family, was observed to be a serious pathogen in human respiratory infections during childhood. Meanwhile, several animal models have been established to study the virus-host interactions and pathogenic effects. Mainly, small laboratory animals like mice and cotton rats have been used, although the usage of these

Oliver Schildgen; Arne Simon; John Williams

2007-01-01

244

Applications of ultrasmall superparamagnetic iron oxide contrast agents in the MR study of animal models  

Microsoft Academic Search

Ultrasmall superparamagnetic iron oxide nanoparticles have been widely used during the past decade as MR intravascular contrast agents in the study of animal models. Such agents enhance both T1 and T2\\/T2* relaxation, although for animal studies it is the later type of enhancement that is most commonly exploited. Their strong microscopic intravascular susceptibility effect enables the local blood volume distribution

Ed X. Wu; Haiying Tang; Jens H. Jensen

2004-01-01

245

Mitochondrial DNA Damage and Animal Longevity: Insights from Comparative Studies  

PubMed Central

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

Pamplona, Reinald

2011-01-01

246

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.

Hayashi, Hiromitsu

2011-01-01

247

Imaging Primary Lung Cancers in Mice to Study Radiation Biology  

PubMed Central

Purpose To image a genetically engineered mouse model of non-small cell lung cancer with micro-CT to measure tumor response to radiation therapy. Methods and Materials The Cre-loxP system was utilized 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 five-fold. 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.; Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.; Perez, Bradford A.; Santiago, Philip M.; Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen; Weissleder, Ralph; Jacks, Tyler

2010-01-01

248

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

249

Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies  

SciTech Connect

The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors including histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.

Ward, J.M.; Quander, R.; Devor, D.; Wenk, M.L.; Spangler, E.F.

1986-09-01

250

Age- and Gender-Related Changes in Ventricular Performance in Wild-Type FVB/N Mice as Evaluated by Conventional and Vector Velocity Echocardiography Imaging: A Retrospective Study.  

PubMed

Detailed studies in animal models to assess the importance of aging animals in cardiovascular research are rather scarce. The increase in mouse models used to study cardiovascular disease makes the establishment of physiologic aging parameters in myocardial function in both male and female mice critical. Forty-four FVB/N mice were studied at multiple time points between the ages of 3 and 16 mo using high-frequency echocardiography. Our study found that there is an age-dependent decrease in several systolic and diastolic function parameters in male mice, but not in female mice. This study establishes the physiologic age- and gender-related changes in myocardial function that occur in mice and can be measured with echocardiography. We report baseline values for traditional echocardiography and advanced echocardiographic techniques to measure discrete changes in cardiac function in the commonly employed FVB/N strain. PMID:23791351

Koch, Sheryl E; Haworth, Kevin J; Robbins, Nathan; Smith, Margaret A; Lather, Navneet; Anjak, Ahmad; Jiang, Min; Varma, Priyanka; Jones, W Keith; Rubinstein, Jack

2013-06-19

251

From mice to men: What can animal models tell us about the relationship between mental health and physical activity?  

Microsoft Academic Search

Physical activity has been associated with numerous benefits that extend to mental health, although how these benefits are accrued is not clear. The notion that animal research can prove useful in this regard may initially seem irrelevant and even inapplicable. However, there is a growing body of evidence, focusing in particular on exercise, to suggest that the biochemical changes induced

Gary Remington

2009-01-01

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

Vitamin C redox reactions in blood of normal and malaria-infected mice studied with isoascorbate as a nonisotopic marker.  

PubMed

It has been suggested that the host antimalarial response depends in part on phagocyte-derived oxidants and that the parasite itself exerts an oxidative stress on its erythrocytic environment. Intraerythrocytic malaria parasites are particularly susceptible to being damaged by oxidative drugs, several of which are under development as chemotherapeutic agents. Thus the antioxidant status and associated regulatory mechanisms of the blood during malaria infection are of great interest. The important antioxidant ascorbate (AH-) and isoascorbate (IAH-), an isomer that does not occur naturally in animals, were found to have similar redox properties. We therefore assessed the usefulness of IAH- as a marker for studies of AH- handling in vivo and in vitro under normal conditions and in murine malaria infection. DHIA added to whole blood from normal or Plasmodium vinckei-infected mice in vitro was rapidly taken up into blood cells and reduced to IAH-. Intracellular IAH- derived from the exogenous DHIA was released into the plasma by blood cells from malaria-infected mice but not those from normal mice. Uptake and reduction of DHIA had no effect on plasma or cellular levels of AH- under these conditions. IAH- injected i.v. into either normal or P. vinckei-infected mice was rapidly cleared in both cases and led to an increase in plasma levels of AH-; this suggested displacement of the latter from some intracellular site, presumably not associated with blood cells. DHIA administered as an intravascular bolus into either normal or malaria-infected mice was rapidly reduced. However, in contrast to the in vitro situation, the concentration of plasma IAH- derived from the injected DHIA was approximately the same in both the infected and control animals. The IAH- so formed disappeared quickly from the plasma. Intravenous injection of DHIA into malaria-infected mice caused a rapid, prolonged increase in the proportion of plasma vitamin C in the form of DHA, whereas in uninfected mice there was a transient decrease in plasma DHA followed by normalisation. The changes in plasma AH- and DHA following IV injection of a single dose of DHA closely paralleled those seen after DHIA administration. These observations indicate that: (i) blood cells from normal and malaria-infected mice take up and reduce DHIA in a similar fashion, but they have different ways of handling the resulting IAH-; (ii) cells other than blood cells are important in the reduction of plasma DHIA and DHA in vivo; (iii) malaria-infected mice are less capable of handling oxidative challenge than normal ones; (iv) in some circumstances IAH- and DHIA may be useful nonisotopic markers for studies of vitamin C handling in vitro and in vivo. PMID:9101245

Iheanacho, E N; Hunt, N H; Stocker, R

1995-03-01

254

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.

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

255

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

PubMed

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

2011-10-28

256

Sperm-Head Morphology Study in B6C3F1 Mice Following Inhalation Exposure to 1,3-Butadiene: Final Technical Report.  

National Technical Information Service (NTIS)

The present report describes the results of a study of the morphology of epididymal sperm heads of B6C3F1 mice that were exposed to varying concentrations of 1,3-butadiene. During the fifth post-exposure week, the animals were killed and examined for gros...

P. L. Hackett B. J. McClanahan M. G. Brown R. L. Buschbom M. L. Clark

1988-01-01

257

[Effects of heptapeptide selank on the content of monoamines and their metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study].  

PubMed

The effect of heptapeptide selank on the content of neurotransmitter monoamines and its metabolites in the brain structures of BALB/C and C57Bl/6 line mice under conditions of the open-field test were studied. Significant interstrain differences in the content of norepinephrine (NE), dopamine (DA), serotonin (5-HT) as well as in the levels of their metabolites in hippocampus, hypothalamus, striatum and frontal cortex of C57Bl/6 and BALB/C mice were demonstrated. In particular, the content of 5-HT and its metabolite 5-oxyindolacetic acid (5-HIAA) in hippocampus of BALB/C mice (with passive stress response) was higher than in the same structure of C57Bl/6 (stress-susceptible) animals. The injection of selank (0.3 mg/kg) led to an increase in the NE level in the hypothalamus of both mice strains. At the same time, selank produced opposite effects on the content of DA metabolites: the concentrations of dioxyphenylacetic (DOPAC) and homovanillic (HVA) acids were found to increase in frontal cortex and hippocampus of C57Bl/6 mice, while the same parameters in BALB/C mice were demonstrated to decrease. Selank induced a decrease in 5-HT and 5-HIAA levels in the hippocampus of BALB/C mice, but did not affect these parameters in C57Bl/6 animals. The obtained results are indicative of selectivity of the anxiolytic effects of selank. PMID:19093364

Narkevich, V B; Kudrin, V S; Klodt, P M; Pokrovski?, A A; Kozlovskaia, M M; Ma?ski?, A I; Raevski?, K S

258

Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.  

PubMed

The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value. PMID:22571623

de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

2012-06-25

259

How a Child Builds Its Brain: Some Lessons from Animal Studies of Neural Plasticity  

Microsoft Academic Search

Although the potential vulnerability of children's brain development is generally recognized, relatively little is known about the timing, resiliency, or mechanisms involved. While animal research should be applied only cautiously to human policy, some findings do have important clinical implications. This paper briefly reviews animal studies demonstrating the effects of experience on brain structure. Contemporary theories emphasize the self-organizing potential

James E. Black

1998-01-01

260

Ethics and Animal Welfare Evaluations in South East Asian Zoos: A Case Study of Thailand  

Microsoft Academic Search

Concern for zoo animals is palpable throughout society in many countries in South East Asia. It is important to understand problems of animal welfare in order for zoos to make significant improvement in maintaining high standards. With a case study of 3 zoos in Thailand, this article presents results for the first time on how ethics and wel- fare evaluations

Govindasamy Agoramoorthy; Bernard Harrison

2002-01-01

261

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

262

Conditional Animal Models for the Study of Lipid Metabolism and Lipid Disorders  

Microsoft Academic Search

The advent of technologies that allow conditional mutagenesis has revolutionized our ability to explore gene functions and to establish animal models of human diseases. Both aspects have proven to be of particular importance in the study of lipid-related disorders. Classical approaches to gene inactivation by conventional gene targeting strategies have been successfully applied to generate animal models like the LDL

H. H. Bock; J. Herz; P. May

263

An Exploratory Study of Animal-Assisted Interventions Utilized by Mental Health Professionals  

Microsoft Academic Search

This study implemented an exploratory analysis to examine how a sample of mental health professionals incorporates specific animal-assisted techniques into the therapeutic process. An extensive review of literature related to animal-assisted therapy (AAT) resulted in the identification of 18 techniques and 10 intentions for the practice of AAT in mental health. The techniques and intentions, along with demographic queries, were

Dana M. OCallaghan; Cynthia K. Chandler

2011-01-01

264

An Exploratory Study of Animal-Assisted Interventions Utilized by Mental Health Professionals  

ERIC Educational Resources Information Center

|This study implemented an exploratory analysis to examine how a sample of mental health professionals incorporates specific animal-assisted techniques into the therapeutic process. An extensive review of literature related to animal-assisted therapy (AAT) resulted in the identification of 18 techniques and 10 intentions for the practice of AAT in…

O'Callaghan, Dana M.; Chandler, Cynthia K.

2011-01-01

265

Sensitivity analysis by experimental design and metamodelling: Case study on simulation in national animal disease control  

Microsoft Academic Search

Simulation is a frequently applied tool in the discipline of animal health economics. Application of sensitivity analysis, however, is often limited to changing only one factor at a time (OAT designs). In this study, the statistical techniques of Design of Experiments (DOE) and regression metamodelling were applied to a simulation model de- veloped to support decision making in national animal

Antonie Vonk Noordegraaf; Mirjam Nielen; Jack P. C. Kleijnen

2003-01-01

266

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

267

Loss of Normal Profilaggrin and Filaggrin in Flaky Tail (ft\\/ft) Mice: an Animal Model for the Filaggrin-Deficient Skin Disease Ichthyosis Vulgaris  

Microsoft Academic Search

Flaky tail (gene symbol ft) is an autosomal recessive mutation in mice that results in a dry, flaky skin, and annular tail and paw constrictions in the neonatal period. Previous studies demonstrated that the ft mutation maps to the central region of mouse chromosome 3, in the vicinity of the epidermal differentiation complex, a gene locus that includes many nonkeratin

Richard B. Presland; Dawnalyn Boggess; S. Patrick Lewis; Christopher Hull; Philip Fleckman; John P. Sundberg

2000-01-01

268

Evaluation of the Experimental Inoculation of Cryptococcus albidus and Cryptococcus laurentii in Normal Mice: Virulence Factors and Molecular Profile Before and After Animal Passage  

Microsoft Academic Search

The genus Cryptococcus includes free-developing species, a few of which are of medical importance. Some, such as C. neoformans and C. gattii, cause infections in man frequently and C. albidus and C. laurentii cause less so. The aims of this study were to evaluate organ colonization after inoculation of C. albidus and C. laurentii isolates in normal BALB\\/c mice, the

Reginaldo dos Santos Pedroso; Joseane Cristina Ferreira; Marco Aurélio Sicchiroli Lavrador; Claudia Maria Leite Maffei; Regina Celia Candido

2009-01-01

269

Dopamine, kidney, and hypertension: studies in dopamine receptor knockout mice  

PubMed Central

Dopamine is important in the pathogenesis of hypertension because of abnormalities in receptor-mediated regulation of renal sodium transport. Dopamine receptors are classified into D1-like (D1, D5) and D2-like (D2, D3, D4) subtypes, all of which are expressed in the kidney. Mice deficient in specific dopamine receptors have been generated to provide holistic assessment on the varying physiological roles of each receptor subtype. This review examines recent studies on these mutant mouse models and evaluates the impact of individual dopamine receptor subtypes on blood pressure regulation.

Wang, Xiaoyan; Villar, Van Anthony M.; Armando, Ines; Eisner, Gilbert M.; Felder, Robin A.

2013-01-01

270

Study on Acetogenin against Radiation-induced Hepatic Biochemical Alterations in Mice  

Microsoft Academic Search

The aim of the present study was to evaluate the radioprotective effect of Acetogenin (AE) on Swiss albino mice against radiation induced hepatic biochemical alterations. Swiss albino mice (6-8 weeks) were divided into three groups. Group I (Normal) was without any treatment. Group II (Control) was only irradiated group (8 Gy). Group III (AE+Irradiated): Mice in this group received AE

A. L. Bhatia; Raka Kamal; Gulshan Verma; K. V. Sharma; Megha Jain; Sharad Vats

2008-01-01

271

Effects of risedronate in Runx2 overexpressing mice, an animal model for evaluation of treatment effects on bone quality and fractures.  

PubMed

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 ?g/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 ?g/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 ?g/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures. PMID:21455736

Geoffroy, Valerie; Paschalis, Eleftherios P; Libouban, Helene; Blouin, Stephane; Ostertag, Agnes; Chappard, Daniel; Cros, Magali; Phipps, Roger; de Vernejoul, Marie-Christine

2011-04-01

272

Electron microscopic study of plant-animal cell fusion  

Microsoft Academic Search

Summary Avian erythrocytes and protoplasts isolated from mesophyll cells of tobacco plants were suspended in 1% protease, agglutinated with polyethylene glycol (PEG) and subsequently fused upon elution of the PEG. The fusion reaction was monitored by scanning (SEM) and transmission (TEM) electron microscopy. SEM studies showed a marked difference in the topography of agglutinated cells. During, and subsequent to fusion,

George E. Willis; James X. Hartmann; Edward D. de Lamater

1977-01-01

273

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

274

Olfactory sensitivity for six amino acids: a comparative study in CD1 mice and spider monkeys  

Microsoft Academic Search

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\\u000a ?0.1 ppm (parts per million) from the odorless solvent, and with three of the six stimuli the best-scoring animals were even\\u000a able to detect concentrations <0.1 ppb (parts per billion). Three

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

275

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies  

PubMed Central

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable.

2011-01-01

276

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies.  

PubMed

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable. PMID:21943025

Shineman, Diana W; Basi, Guriqbal S; Bizon, Jennifer L; Colton, Carol A; Greenberg, Barry D; Hollister, Beth A; Lincecum, John; Leblanc, Gabrielle G; Lee, Linda Bobbi H; Luo, Feng; Morgan, Dave; Morse, Iva; Refolo, Lorenzo M; Riddell, David R; Scearce-Levie, Kimberly; Sweeney, Patrick; Yrjänheikki, Juha; Fillit, Howard M

2011-09-28

277

n-3 fatty acids and lipoproteins: Comparison of results from human and animal studies  

Microsoft Academic Search

The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both\\u000a animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were\\u000a followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of

William S. Harris

1996-01-01

278

Computer assisted biokinetic studies of radiopharmaceuticals in animals and humans  

SciTech Connect

The labelling of plasmin with technetium-99m was first studied in our department. A stable kit is obtained by lyophilizing plasmin (NOVO Industry A/S, Denmark), stannous chloride and sodium chloride at low pH in nitrogen atmosphere. Pertechnetate is added to this kit and incubated during one hour. The labelling yield of /sup 99m/Tc-plasmin recorded by the use of gel chromatography column scanning averaged 85%. Artificial thrombi were formed in the jugular vein of rabbits by trapping iron particles injected into an ear vein. The kinetics of /sup 99m/Tc-plasmin uptake by the thrombi was studied with dynamic scintillation camera measurements. To study the whole body distribution in patients with a scintillation camera we used about 80 MBq (approx. 2 mCi) of /sup 99m/Tc-plasmin. The highest activity uptake 1 to 2 h after injection was in liver and spleen (35%) and the activity in the legs was about 15%. The absorbed dose per unit of administered activity in whole body was estimated to be about 7 ..mu..Gy/MBq (25 mrad/mCi). In routine clinical measurements about 10 to 30 MBq (0.3 to 0.9 mCi) /sup 99m/Tc-plasmin was injected and measurements were performed with a hand detector. This method is now used routinely in several hospitals of southern Sweden and in London for the diagnosis of deep venous thrombosis.

Darte, L.; Persson, B.R.R.; Strand, S.E.; Olsson, C.G.

1981-06-01

279

Proteomic study on gender differences in aging kidney of mice  

PubMed Central

Background This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Results This proteomic analysis detected age-related changes in protein expression in 55 protein-spots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES) of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on age-related changes in expression levels of proteins and related modifications. This pilot study is still far from providing candidates for aging-biomarkers. However, we suggest that the analysis of these proteins could suggest mechanisms of cellular aging in kidney, and improve the kidney selection for transplantation.

Amelina, Hanna; Cristobal, Susana

2009-01-01

280

Multiple CNS nicotinic receptors mediate l-dopa-induced dyskinesias: Studies with parkinsonian nicotinic receptor knockout mice.  

PubMed

Accumulating evidence supports the idea that drugs acting at nicotinic acetylcholine receptors (nAChRs) may be beneficial for Parkinson's disease, a neurodegenerative movement disorder characterized by a loss of nigrostriatal dopaminergic neurons. Nicotine administration to parkinsonian animals protects against nigrostriatal damage. In addition, nicotine and nAChR drugs improve l-dopa-induced dyskinesias, a debilitating side effect of l-dopa therapy which remains the gold-standard treatment for Parkinson's disease. Nicotine exerts its antidyskinetic effect by interacting with multiple nAChRs. One approach to identify the subtypes specifically involved in l-dopa-induced dyskinesias is through the use of nAChR subunit null mutant mice. Previous work with ?2 and ?6 nAChR knockout mice has shown that ?6?2* nAChRs were necessary for the development/maintenance of l-dopa-induced abnormal involuntary movements (AIMs). The present results in parkinsonian ?4 nAChR knockout mice indicate that ?4?2* nAChRs also play an essential role since nicotine did not reduce l-dopa-induced AIMs in such mice. Combined analyses of the data from ?4 and ?6 knockout mice suggest that the ?6?4?2?3 subtype may be critical. In contrast to the studies with ?4 and ?6 knockout mice, nicotine treatment did reduce l-dopa-induced AIMs in parkinsonian ?7 nAChR knockout mice. However, ?7 nAChR subunit deletion alone increased baseline AIMs, suggesting that ?7 receptors exert an inhibitory influence on l-dopa-induced AIMs. In conclusion, ?6?2*, ?4?2* and ?7 nAChRs all modulate l-dopa-induced AIMs, although their mode of regulation varies. Thus drugs targeting one or multiple nAChRs may be optimal for reducing l-dopa-induced dyskinesias in Parkinson's disease. PMID:23831952

Quik, Maryka; Campos, Carla; Grady, Sharon R

2013-07-04

281

[Maxillary expansion with magnetic force: an animal experimental study].  

PubMed

Two adult rhesus monkeys were chosen for the experimental study of maxillary expansion with magnetic force. The duration of experiment was 70 days. The following methods were applied: 1. measuring the width between the two canines and the width between the two first molars on the casts, 2. taking occlusal radiographs for the observation of premaxillary and midpalatal sutures. 3. observing the histological sections under the microscope. The results showed the width of 3 to 3 and the width of 6 to 6 significantly increased, associating with the adaptation of periodontal tissues to the action of magnetic force. PMID:12078180

Liang, W; Xu, Y; Zhang, X

1998-02-01

282

Zinc supplementation aggravates body fat accumulation in genetically obese mice and dietary-obese mice  

Microsoft Academic Search

A perturbation of zinc metabolism has been noted in numerous laboratory animals with diabetes and obesity. The effects of\\u000a zinc supplementation on body fat deposition in two types of experimental obese mice: genetically obese (ob\\/ob) mice and high-fat\\u000a diet-induced ICR obese (HF) mice were investigated in this study. Their lean controls were +\\/? mice, and ICR on basal diet,\\u000a respectively.

Ming-Der Chen; Pi-Yao Lin; Vie Cheng; Wen-Han Lin

1996-01-01

283

Social work practitioners and the human-companion animal bond: a national study.  

PubMed

Extensive research documents powerful relationships between humans and companion animals, and 62 percent of U.S. households report having a companion animal. Social workers are likely to work with individuals and families with companion animals; thus, the inclusion of such animals in both practice and research as a natural extension of social work with humans, and their challenges, coping mechanisms, and resiliency factors, seems called for. Yet there is little in the social work literature that identifies what social workers are doing in this area. Thus, this descriptive study sought to explore nationally what social work practitioners know and are doing in the area of the human and companion animal relationships. Findings include that social work practitioners appear to have basic knowledge of the negative and positive relationships between humans and companion animals. About one-third are including questions about companion and other animals in their intake assessments, and a little less than 25 percent are including companion and other animals in their intervention practice. The vast majority have had no special training or coursework to do so. Implications for these and other findings are discussed, and recommendations for social work research, education, and practice are offered. PMID:20069939

Risley-Curtiss, Christina

2010-01-01

284

Adolescent development of forebrain stimulant responsiveness: insights from animal studies.  

PubMed

Although initiation of drug abuse occurs primarily during adolescence, little is known about the central effects of nicotine and other abused drugs during this developmental period. Here evidence, derived from studies in rodents, is presented that suggests that tobacco use initiation during early adolescence results from a higher reward value of nicotine. The developmental profiles of the rewarding effects of other abused drugs, such as cocaine, differ from that of nicotine. Using in situ hybridization to quantify mRNA levels of the immediate early gene, cfos, the neuronal activating effects of nicotine in limbic and sensory cortices at different developmental stages are evaluated. Significant age changes in basal levels of cfos mRNA expression in cortical regions are observed, with a peak of responding of limbic cortices during early adolescence. A changing pattern of nicotine-induced neuronal activation is seen across the developmental spectrum, with unique differences in both limbic and sensory cortex responding during adolescence. An attentional set-shifting task was also used to evaluate whether the observed differences during adolescence reflect early functional immaturity of prefrontal cortices that regulate motivated behavior and psychostimulant responding. The finding of significantly better responding during adolescence suggests apparent functional maturity of prefrontal circuits and greater cognitive flexibility at younger ages. These findings in rodent models suggest that adolescence is a period of altered sensitivity to environmental stimuli, including abused drugs. Further efforts are required to overcome technical challenges in order to evaluate drug effects systematically in this age group. PMID:15251884

Leslie, Frances M; Loughlin, Sandra E; Wang, Ruihua; Perez, Lilyanna; Lotfipour, Shahrdad; Belluzzia, James D

2004-06-01

285

Enumeration of probiotic pediococci in animal feed: interlaboratory study.  

PubMed

An enumeration method to be used as official control under Council Directive 70/524/EEC for probiotic pediococci used as feed additives was validated for consideration for adoption as Comitée Européen de Normalisation (CEN) and ISO standards. Seventeen laboratories in 11 European countries carried out an interlaboratory study. A spread plate method following BS ISO 15214:1998 using 4 different agars [MRS, acidified MRS, MRS with triphenyl tetrazolium chloride (TTC), and a newly developed pediococci selective medium (PSM)] was validated. Precision data in terms of repeatability (r) and reproducibility (R) of the method for each medium using different feeding stuffs with a high and a low inoculation level were determined. Pediococci were present in the samples in mixtures with other probiotics. The enumeration of pediococci on all agars showed an RSDr value of 0.4-3.1% and an RSDR of 1.3-4.8%. MRS agar was preferred, followed by acidified MRS and MRS + TTC agar. All 4 media gave similar counts. Depending on the presence and concentration of other probiotic, such as enterococci, lactobacilli, and yeast, acidified MRS or MRS + TTC agar are recommended. The PSM was selective for pediococci and can be used if this species is present at a concentration more than 10-fold lower than other species that can grow on the MRS agars. The methodology with all 4 media is not applicable to mineral feed. PMID:14509440

Leuschner, Renata G K; Bew, Jan; Simpson, Paul J; Ross, Paul R; Stanton, Catherine

286

Electron microscope study of the kinetic apparatus in animal sperm cells  

Microsoft Academic Search

A comparative study of the development and fine structure of the kinetic apparatus of sperm cell of several animal species is made. The description is based on the electron microscope examination of the morphologic changes occurring during spermatid maturation.

J. Roberto Sotelo; Omar Trujillo-Cenóz

1958-01-01

287

Guidance for Industry: Good Target Animal Study Practices: Clinical Investigators and Monitors.  

National Technical Information Service (NTIS)

The purpose of this guidance document is to make recommendations to investigators and monitors concerning the conduct of clinical studies evaluating the performance of investigational new animal drugs. The Center for Veterinary Medicine (CVM) has identifi...

1997-01-01

288

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.

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

289

In vivo toxicity studies of europium hydroxide nanorods in mice  

SciTech Connect

Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu{sup III}(OH){sub 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 mg kg{sup -1} day{sup -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 euthanized on days 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.

Patra, Chitta Ranjan [Department of Biochemistry and Molecular Biology, 200 First Street S.W, Guggenheim 1321A, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States)], E-mail: patra.chittaranjan@mayo.edu; Abdel Moneim, Soha S. [Gastroenterology and Hepatology, GI Research Unit, 200 First Street S.W, Guggenheim 1034, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Wang, Enfeng; Dutta, Shamit; Patra, Sujata [Department of Biochemistry and Molecular Biology, 200 First Street S.W, Guggenheim 1321A, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Eshed, Michal [Department of Chemistry and Kanbar Laboratory for Nanomaterials, Bar-Ilan University Center for Advanced Materials and Nanotechnology, Bar-Ilan University, Ramat-Gan 52900 (Israel); Mukherjee, Priyabrata [Department of Biochemistry and Molecular Biology, 200 First Street S.W, Guggenheim 1321A, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Department of Biomedical Engineering, 200 First Street S.W, Guggenheim 1334, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Gedanken, Aharon [Department of Chemistry and Kanbar Laboratory for Nanomaterials, Bar-Ilan University Center for Advanced Materials and Nanotechnology, Bar-Ilan University, Ramat-Gan 52900 (Israel); Shah, Vijay H. [Gastroenterology and Hepatology, GI Research Unit, 200 First Street S.W, Guggenheim 1034, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Mukhopadhyay, Debabrata [Department of Biochemistry and Molecular Biology, 200 First Street S.W, Guggenheim 1321A, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States); Department of Biomedical Engineering, 200 First Street S.W, Guggenheim 1334, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905 (United States)

2009-10-01

290

Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study  

PubMed Central

Background Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice’s hematocrit was about 50% lower than that of controls (p??1.4) and 115 were strongly down-regulated (normalized ratio?mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail.

2012-01-01

291

Studies of Hard and Soft Tissue Elemental Compositions in Mice and Rats Subjected to Simulated Microgravity  

Microsoft Academic Search

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.

Rahul Mehta; Hannah M. Fitch; Nawab Ali; Michael Soulsby; Parimal Chowdhury

2009-01-01

292

Radioinduced Leukemia. An Introduction to the Study of Experimental Leukemia in Mice.  

National Technical Information Service (NTIS)

This thesis attempts to gain insight into any mechanisms involved in the onset of irradiation-induced leukemia in mice, then to show up the presence of a virus in the same animals. Concerning the mechanisms of radio-induced leukemias the pathogenic factor...

P. P. Baudon

1974-01-01

293

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...

294

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

PubMed Central

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

Fossmark, Reidar; Qvigstad, Gunnar; Waldum, Helge L

2008-01-01

295

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

PubMed

Gastric hypoacidity and hypergastrinaemia are seen in several conditions associated with an increased risk of gastric malignancy. Hypoacidity and hypergastrinaemia are closely related and their long-term effects are difficult to study separately in patients. Studies using animal models can provide valuable information about risk factors and mechanisms in gastric cancer development as the models allow a high degree of intervention when introducing or eliminating factors possibly affecting carcinogenesis. In this report, we briefly review findings from relevant animal studies on this topic. Animal models of gastric hypoacidity and hypergastrinaemia provide evidence hypergastrinaemia is a common causative factor in many otherwise diverse settings. In all species where sufficient hypoacidity and hypergastrinaemia have been induced, a proportion of the animals develop malignant lesions in the gastric oxyntic mucosa. PMID:18350594

Fossmark, Reidar; Qvigstad, Gunnar; Waldum, Helge-L

2008-03-21

296

[Experimental study of immunological function regulated by Fufang Hongjingtian capsule in mice].  

PubMed

The aim of this study was to investigate the immunological function regulated by Fufang Hongjingtian capsule (HJT) in mice. The mice were given ig HJT 25, 250 and 750 mg/kg, once daily, for 30 - 38 d, respectively. The mice in control group were given ig corresponding solvent. After the last time of administration, the immunological parameters of the mice were measured. The results showed that compared with negative control group, the delayed type hypersensitivity, spleen lymphocyte proliferation and number of spleen IgM antibody forming cells increased in HJT groups. In conclusion the HJT has the effect to improve the immunological functions of mice. PMID:22391194

Wei, Ri-Bao; Wang, Yong-Xin; Yang, Yue; Cui, Shao-Yuan; Shi, Suo-Zhu

2012-02-01

297

Facilitating Multimodal Preclinical Imaging Studies in Mice by Using an Immobilization Bed  

PubMed Central

We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve image registration for multimodal scans and for longitudinal preclinical imaging studies. Stationary pegs were placed such that they effectively immobilized mice and reduced set-up time. 22Na fiducial markers were placed into the pegs at unique depths to provide 3D references to facilitate image registration. Multiple users registered positron emission tomographic (PET) and CT data obtained with and without the bed to examine the effect of the bed on registration accuracy and interuser variability. The image registrations performed by different users were evaluated for their similarity by using the Entropy Correlation Coefficient as a metric. The immobilization bed significantly reduced variations in body movement and interuser variability. Average differences in quantification of tumor PET signal among users when registering images without versus with the fiduciary-marker bed fell from 9.1% to 0.8% for maximal percentage injected dose per gram (%ID/g), from 15.6% to 2.3% for mean %ID/g, and from 9.4% to 0.7% for the 90th percentile of the maximum %ID/g. The bed improves animal immobilization, greatly reduces interuser variability, and supports registration of image data acquired from different imaging sessions.

Nelson, Geoffrey S; Perez, Jessica; Colomer, Marta V; Ali, Rehan; Graves, Edward

2011-01-01

298

Ultrasound Biomicroscopy for Longitudinal Studies of Carotid Plaque Development in Mice: Validation with Histological Endpoints  

PubMed Central

Atherosclerosis is responsible for the death of thousands of Americans each year. The carotid constriction model of plaque development has recently been presented as a model for unstable plaque formation in mice. In this study we 1) validate ultrasound biomicroscopy (UBM) for the determination of carotid plaque size, percent stenosis, and plaque development in live animals, 2) determine the sensitivity of UBM in detecting changes in blood flow induced by carotid constriction and 3) test whether plaque formation can be predicted from blood flow parameters measured by UBM. Carotid plaques were induced by surgical constriction in Apo E?/? mice. Arteries were imaged bi-weekly by UBM, at which time PW-Doppler measurements of proximal blood flow, as well as plaque length and percent stenosis were determined. Histology was performed 9 weeks post surgery. When compared to whole mount post-mortem measurements, UBM accurately reported carotid plaque length. Percent stenosis, based on transverse B-mode UBM measurements, correlated well with that calculated from histological sections. PW-Doppler revealed that constriction reduced maximum systolic velocity (vmax) and duration of the systolic velocity peak (ts/tt). Pre-plaque (2 week post-surgery) PW-Doppler parameters (vmax and ts/tt) were correlated with plaque length at 9 weeks, and were predictive of plaque formation. Correlation of initiating PW-Doppler parameters (vmax and ts/tt) with resulting plaque length established the degree of flow disturbance required for subsequent plaque development and demonstrated its power for predicting plaque development.

Harmon, Erin Y.; Fronhofer, Van; Keller, Rebecca S.; Feustel, Paul J.; Brosnan, M. Julia; von der Thusen, Jan H.; Loegering, Daniel J.; Lennartz, Michelle R.

2012-01-01

299

Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats  

SciTech Connect

The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

Justesen, D.R.

1981-10-01

300

Antagonism Between Luminal and Caffeine, Studied by the Use of Radioisotopes; RECHERCHES SUR LES BARBITURIQUES RADIOACTIFS: LA DISTRIBUTION DU LUMINAL DANS L'ORGANISME ANIMAL EN PRESENCE DE CAFEINE  

Microsoft Academic Search

The normal pattern of distribution of luminal in the animal organism was ; determined in mice using a tracer technique. The effect of an antagonistic drug, ; e.g., caffeine, on this normal distribution pattern was studied. The results ; confirmed the hypothesis of the in vivo breaking of the barbituric ring. ; (J.S.R.);

B. Aliprandi; R. Masironi

1959-01-01

301

Neuroprotective effect of L-dopa on dopaminergic neurons is comparable to pramipexol in MPTP-treated animal model of Parkinson's disease: a direct comparison study.  

PubMed

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the pars compacta of the substantia nigra. Levodopa (l-dopa) and dopamine agonists have been most commonly used for symptomatic treatment. However, there are discrepancies between clinical and experimental data with respect to the neuroprotective effects of these drugs on dopaminergic neurons. In this study, to determine whether L-dopa is toxic or dopamine agonist is neuroprotective to dopaminergic neurons, we evaluated the neuroprotective properties of l-dopa and the pramipexol (PPX), one of dopamine agonists, with a focus on the regulatory effects of the anti-oxidant properties and cell survival or apoptotic signal pathways in the same experimental design, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD animals. The glutathione level in MPTP-treated mice was significantly increased by PPX administration but not by L-dopa treatment. The expression of phosphorylated extracellular signal regulated kinase in MPTP-treated mice was significantly increased only with L-dopa treatment. Treatment with either l-dopa or PPX in MPTP-treated mice led to significantly decreased expressions of JNK phosphorylation, Bax, and cytochrome c and to an increased level of Bcl-2 expression with a similar degree, compared with the levels in MPTP-only treated mice. Immunohistochemical analysis showed that both L-dopa and PPX increased significantly survival of dopaminergic neurons in MPTP-treated mice. Our study demonstrated that both l-dopa and PPX had comparable neuroprotective properties for dopaminergic neurons in MPTP-treated PD animal models, through modulation of cell survival and apoptotic pathways. PMID:19765187

Shin, Jin Young; Park, Hyun-Jung; Ahn, Young Hwan; Lee, Phil Hyu

2009-09-16

302

Induction of PDK4 in the heart muscle of JVS mice, an animal model of systemic carnitine deficiency, does not appear to reduce glucose utilization by the heart  

Microsoft Academic Search

Pyruvate dehydrogenase kinase 4 (PDK4) mRNA has been reported as an up-regulated gene in the heart and skeletal muscle of carnitine-deficient juvenile visceral steatosis (JVS) mice under fed conditions. PDK4 plays an important role in the inhibition of glucose oxidation via the phosphorylation of pyruvate dehydrogenase complex (PDC). This study evaluated the meaning of increased PDK4 mRNA in glucose metabolism

Miharu Ushikai; Masahisa Horiuchi; Keiko Kobayashi; Sadayuki Matuda; Akio Inui; Toru Takeuchi; Takeyori Saheki

2011-01-01

303

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.

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

2009-01-01

304

Biophysical study of mice blood after whole body irradiation  

NASA Astrophysics Data System (ADS)

The immediate of whole body fractionated doses of 137Cs gamma rays totalling 13 Gy on mice as well as the late effects of accumulative dose of 10 Gy (8 days after exposure) were studied. Changes due to gamma irradiation in hemoglobin conductivity and buffer capacity indicate the appearance of hydrophobic groups and changes in hydrophilic/hydrophobic ratio. These changes demonstrate different degrees of unfolding and refolding of the hemoglobin molecule. The viscosity coefficient of hemoglobin is found to increase at fractionated doses of 7 and 13 Gy. Such effect seems to be due to aggregation of the protein part of hemoglobin. The fractionated dose of 13 Gy causes changes in the electronic state of oxyhemoglobin indicated by an increase in methemoglobin which reduces biological activity.

El Din, Alsha A. Saad; Desouky, Omar S.; El Behay, Amin Z.; El Sayed, Anwar A.

1996-05-01

305

Are Covered Stents Really Effective at Closing Esophagotracheal Fistulas? Results of an Animal Study  

SciTech Connect

Purpose: To determine whether covered self-expanding metal stents successfully exclude experimentally created esophagotracheal fistulas.Methods: Esophagotracheal fistulas were surgically created in the upper third of the esophagus in 12 minipigs and immediately sealed by implantation of a covered self-expanding metal stent (20 mm expanded diameter) in the esophagus. Before the animals were killed, after 3, 7, 14, 28, 30, and 36 days, the position of the stent and the sealing of the fistula were monitored fluoroscopically. The esophagus, trachea, and both lungs were examined histologically.Results: Creation of an esophagotracheal fistula was successful in all cases. All fistulas were widely patent at autopsy. The technical success rate for stent deployment and initial sealing of the fistula was 100%. During follow-up, five stents migrated distally, but none into the stomach. Therefore, the fistula was no longer excluded in five animals. In seven animals the stent sealed the fistula until the death of the animal. Tracheal narrowing necessitated additional tracheal stenting in three animals. Two minipigs died due to aspiration of food. Histologic examination showed signs of aspiration in all animals with stents in place for longer than 2 weeks.Conclusion: This experimental animal study revealed worse results for sealing of esophagotracheal fistulas with covered self-expanding metal stents than have been reported for the clinical use of these devices.

Wagner, Hans-Joachim [Department of Diagnostic Radiology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Stinner, Benno [Department of General Surgery, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Barth, Peter [Department of Pathology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany); Klose, Klaus-Jochen [Department of Diagnostic Radiology, Philipps University, Baldingerstrasse, D-35033 Marburg (Germany)

2000-07-15

306

Long-term toxicity and carcinogenicity studies of cake made from chlorinated flour. 2. Studies in mice.  

PubMed

Male and female Theiller's Original strain mice were fed for 16 and 17 months respectively on diets in which cake, prepared from flours treated with 0, 1250 or 2500 ppm chlorine, formed 79% by weight on a 12.6% moisture basis. Body weights and food intakes were unaffected by flour treatment but all of the animals on cake diets showed significant increases in body weight compared with controls on a standard diet and became obese. Mortalities in the males were not related to treatment, but in the females there was excess mortality in the treated groups compared with the cake control group, after 13 months in the 1250 group and after 15 months in the 2500 group. No consistent treatment-related effects were observed in the haematological, biochemical and renal-function studies. Dose-related increases in heart and kidney weights and a dose-related decrease in ovary weight were seen in females. No evidence of carcinogenicity resulting from flour treatment was obtained but the early ending of the study, necessitated by high mortalities, greatly diminished the value of this finding. Concentrations of covalently bound chlorine in the perirenal fat were positively correlated with treatment level, but were considerably below those present in the lipid content of the diets on which the mice were fed. PMID:6684625

Ginocchio, A V; Fisher, N; Hutchinson, J B; Berry, R; Hardy, J

1983-08-01

307

The last decade of solvent research in animal models of abuse: Mechanistic and behavioral studies  

Microsoft Academic Search

The Last Decade of Animal solvent Abuse Research: Mechanistic and Behavioral Studies. Bowen, S. E., Batis, J.C., Paez-Martinez, N., and Cruz, S.L. Neurotoxicology and Teratology, XX, 2006. The abuse of volatile organic solvents (inhalants) leads to diverse sequelae at levels ranging from the cell to the whole organism. This paper reviews findings from the last 10 years of animal models investigating

Scott E. Bowen; Jeffery C. Batis; Nayeli Paez-Martinez; Silvia L. Cruz

2006-01-01

308

Drosophila melanogaster as a model for studying the function of animal viral proteins  

Microsoft Academic Search

Studies in which Drosophila melanogaster individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are\\u000a reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the\\u000a penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell

L. V. Omel’yanchuk; O. S. Yudina

2011-01-01

309

Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma  

PubMed Central

Taxol is a microtubule inhibitor drug widely used in treatment of many types of cancer. Nephrotoxicity is the most hazardous effect complicating chemotherapy in general and kidney functions must be monitored early during any chemotherapeutic course. The main objective of the present study was to investigate the effect of acute Taxol nephrotoxicity in mice. In the present study Taxol at different doses; MD, ID and MTD (0.6, 1.15 and 1.7 mg/kg), respectively, was given by intra-peritoneal route to 54 adult male mice with an average body weight of 20–25 g. Kidney samples was taken 6, 24, 48 h following administration, fixed in 10% neutral buffered formalin, paraffin sections 5 ?m thick were stained by haematoxylin and eosin and PAS and then examined for histological changes. Samples from animals treated by the maximum dose (MTD = 1.7 mg/kg) for 48 h were fixed in 3% gluteraldehyde in phosphate buffer (pH 7.4) and processed for transmission electron microscope. Taxol given for short duration was found to produce marked degenerative changes in kidney parenchyma even in minimum tolerated dose (MD = 0.6 mg/kg). Individual variations were observed regarding the degree of nephrotoxicity. There was marked loss of renal tubules epithelial lining, damage of brush border and formation of hyaline casts within the damaged tubules. The alterations were in the form of both necrotic and apoptotic changes in the kidney tubules. Focal atrophy of glomerular tufts was also observed. Vascular congestion and degenerative changes in renal blood vessels were occasionally evident in some samples. Ultrastructure study revealed damage of glomerular membrane. Proximal tubule showed loss of basal infoldings, damage of brush border, mitochondrial degeneration and nuclear changes. Distal tubules also showed demarked degenerative changes. Increased frequency of micronuclei proved that Taxol had genotoxic effects in mice bone marrow cells. In conclusion Taxol had nephrotoxic effect on mice kidney that must be considered during its use as a chemotherapeutic agent in human.

Rabah, Samar Omar

2010-01-01

310

Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh.  

PubMed

Despite the wealth of evidence supporting the activation of caspases in Alzheimer's disease (AD), chronic administration of a caspase inhibitor has never been tested in any animal model system. The purpose of the current report was to identify a suitable animal model that displays caspase activation and cleavage of critical proteins associated with AD, and secondly, to undertake a pilot study utilizing the novel caspase inhibitor, quinolyl-valyl-O-methylaspartyl-[-2, 6-difluorophenoxy]-methyl ketone (Q-VD-OPh). Analysis of 12 month-old TgCRND8 mice, which represent an early-onset animal model for AD, indicated the activation of caspase-7 as well as the cleavage of tau and the amyloid precursor protein (APP). Having established that TgCRND8 mice represent a suitable model system to target caspases therapeutically, a prophylactic study was initiated utilizing Q-VD-OPh. Three month-old TgCRND8 mice were injected intraperitoneally three times a week for three months with 10 mg/kg Q-VD-OPh and compared to control mice injected with vehicle. Although there was no apparent effect on extracellular Abeta deposition, chronic treatment with Q-VD-OPh did prevent caspase-7 activation and limited the pathological changes associated with tau, including caspase cleavage. These preliminary findings suggest that further studies examining the utility of Q-VD-OPh as a potential therapeutic compound for the treatment of AD are warranted. PMID:20057974

Rohn, Troy T; Kokoulina, Polina; Eaton, Cody R; Poon, Wayne W

2009-11-05

311

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

312

Studies on tumor incidence in mice exposed to GSM cell-phone radiation [Health Effects  

Microsoft Academic Search

This paper studies on tumor incidence in mice exposed to GSM cell-phone radiation. The first study of lymphomas in female Emu_Pim1 transgenic mice using frequencies and modulations specific to cellular mobile phones was conducted in Australia in which the incidence was shown to be significantly higher (odds ratio, OR = 2.4) in the exposed mice (43%) than in the sham

James C. Lin

2008-01-01

313

A Bayesian methodology for scaling radiation studies from animals to man  

Microsoft Academic Search

This paper describes a Bayesian methodology for integrating studies in experimental animals and humans to obtain a risk estimate for a radionuclide for which no data or very limited human data are available. The method is quite general and is not limited to radiation studies. In fact, it was first developed for chemical toxicants. The methodology is illustrated using studies

W. DuMouchel; P. G. B. Gror

1989-01-01

314

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells  

NASA Astrophysics Data System (ADS)

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

315

Mutation in the CPC motif-containing 6th transmembrane domain affects intracellular localization, trafficking and copper transport efficiency of ATP7A protein in mosaic mutant mice--an animal model of Menkes disease.  

PubMed

Copper is an essential micronutrient for all living organisms. ATP7A protein is a copper-transporting ATPase which plays a vital role in the maintenance of cellular copper homeostasis in mammals. This protein is retained within the trans-Golgi network, but after binding copper it can be translocated to the cell membrane to participate in the efflux of excess Cu. Mutation of the ATP7A gene in humans results in the severe neurodegenerative disorder, Menkes disease. The mouse ATP7A homolog encodes a protein that plays the same role in copper transport. Mosaic mutant mice display a lethal phenotype which resembles Menkes disease, although the underlying molecular defect has not been characterized until now. In the present study we identified a G to C nucleotide exchange in exon 15 of the Atp7a gene in mosaic mutants, which resulted in an arginine to proline substitution in the highly conserved 6th transmembrane domain of the ATP7A protein. This mutated protein was mislocalized in kidney cells isolated from mosaic mutant mice, and following exposure of these cells to increased copper concentrations it was not translocated to the plasma membrane. Disturbance of ATP7A function in mosaic mice results in increased copper accumulation in the small intestine and kidneys, and in Cu deficiency in the brain, liver and heart. Mouse models of Menkes disease belong to the mottled mutant group. The mosaic mutant represents another interesting animal model for Menkes disease that will be of value in research on copper metabolism and transport in mammals. PMID:22089129

Lenartowicz, Ma?gorzata; Grzmil, Pawe?; Shoukier, Moneef; Starzy?ski, Rafa?; Marciniak, Marcin; Lipi?ski, Pawe?

2011-11-16

316

Toxicological Study and Efficacy of Blank and Paclitaxel-Loaded Lipid Nanocapsules After i.v. Administration in Mice  

Microsoft Academic Search

Purpose  Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting entrapment of paclitaxel and increasing its antitumoural\\u000a effect in animal models after i.v. injection. The tolerance and efficacy of LNCs after repeated dose i.v. administration were assessed in mice. The maximum tolerated dose (MTD) and 50% lethal dose (LD50) were studied.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Paclitaxel-loaded LNC formulation was given i.v. at the dose of 12 mg\\/kg

José Hureaux; Frédéric Lagarce; Frédéric Gagnadoux; Marie-Christine Rousselet; Valérie Moal; Thierry Urban; Jean-Pierre Benoit

2010-01-01

317

Animated UI transitions and perception of time: a user study on animated effects on a mobile screen  

Microsoft Academic Search

The capability to present advanced graphics in the present mobile devices can be utilized to improve their usability and overall user experience. Mobile devices have limitations compared to PCs due to their inferior computing power and small screens, but a successful design of animated transitions can hide processing delays and make the user experience smoother. In this paper, we describe

Jussi Huhtala; Ari-Heikki Sarjanoja; Jani Mäntyjärvi; Minna Isomursu; Jonna Häkkilä

2010-01-01

318

Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis  

PubMed Central

Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of a repair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them.

Graves, Dana T.; Kang, Jun; Andriankaja, Oelisoa; Wada, Keisuke; Rossa, Carlos

2013-01-01

319

Inhalation Teratology Study of T-Dodecyl Mercaptan in Rats and Mice with Cover Letter dated 06/12/86.  

National Technical Information Service (NTIS)

Pregnant Charles River CD(trademark)-1 mice and pregnant Charles River COBS(trademark) CD(trademark) rats, randomly assigned to one control group and two t-dodecyl mercaptan treated groups of fifty animals (25 mice and 25 rats) each, were used to determin...

1983-01-01

320

Animal Studies on Medicinal Herbs: Predictability, Dose Conversion and Potential Value.  

PubMed

Animal studies testing medicinal herbs are often misinterpreted by both translational researchers and clinicians due to a lack of information regarding their predictability, human dose equivalent and potential value. The most common mistake is to design or translate an animal study on a milligram per kilogram basis. This can lead to underestimation of the toxicity and/or overestimation of the amount needed for human therapy. Instead, allometric scaling, which involves body surface area, should be used. While the differences in the pharmacokinetic and pharmacodynamic phases between species will inevitably lead to some degree of error in extrapolation of results regardless of the conversion method used, correct design and interpretation of animal studies can provide information that is not able to be provided by in vitro studies, computer modeling or even traditional use. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23553964

Wojcikowski, Ken; Gobe, Glenda

2013-04-01

321

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.

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

2013-01-01

322

Harmonization of Animal Clinical Pathology Testing in Toxicity and Safety Studies  

Microsoft Academic Search

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies

Kurt Weingand; Geoff Brown; Robert Hall; Dai Davies; Kent Gossett; Doug Neptun; Trevor Waner; Toshiaki Matsuzawa; Paul Salemink; Wilhelm Froelke; Jean-Pierre Provost; Gianni Dal Negro; John Batchelor; Mamoru Nomura; Horst Groetsch; Alphons Boink; Jon Kimball; David Woodman; Malcolm York; Eva Fabianson-Johnson; Michel Lupart; Elsa Melloni

1996-01-01

323

Arsenic antagonism studies with monoisoamyl DMSA and zinc in male mice.  

PubMed

Administration of zinc either alone or in combination with monoisoamyl dimercaptosuccinic acid (DMSA) during and post-arsenic exposure was investigated in male mice. The animals were administered 2mgkg(-1) arsenic as sodium arsenite, intraperitoneally, once daily for 5 days either alone or in combination with 10mgkg(-1), zinc (as zinc acetate, orally), 50mgkg(-1) monoisoamyl dimercaptosuccinic acid (MiADMSA) given orally (p.o.), 2h after arsenic administration. Another group of arsenic treated animals was given both zinc (10mgkg(-1)) and MiADMSA (50mgkg(-1), p.o.). Animals were sacrificed 24h after the last dose. In another set of experimentation, arsenic pre-exposed mice (2mgkg(-1), i.p. for 5 days) were treated with saline, zinc, MiADMSA or zinc plus MiADMSA for next 3 days and sacrificed thereafter. Exposure to arsenic led to a significant inhibition of blood ?-aminolevulinic acid dehydratase (ALAD), depletion of glutathione (GSH) level and marginal elevations of zinc protoporphyrin (ZPP). Arsenic exposure caused a significant decrease in hepatic and renal GSH level and an increase in liver oxidized glutathione (GSSG) and liver and kidney thiobarbituric acid reactive substance (TBARS) levels. Concomitant administration of zinc with arsenic provided significant protection to blood ALAD activity while, GSH and ZPP levels remained unaltered. Co-administration of MiADMSA with arsenic significantly prevented accumulation of arsenic in blood, liver and kidney while, zinc had no effect on tissue arsenic concentration. Combined administration of zinc and MiADMSA had no major additional beneficial effects over their individual effects. Interestingly, post-arsenic exposure treatment with MiADMSA provided significant recovery in blood ALAD activity while, zinc supplementation alone had no effect. The best results however, were obtained when MiADMSA was administered along-with zinc. Most of the biochemical variables indicative of hepatic oxidative stress responded favorably to MiADMSA treatment while, zinc administration had no effect. Administration of MiADMSA significantly depleted arsenic concentration from the soft tissues while, combined zinc and MiADMSA had no additional beneficial effect over the individual effect of MiADMSA. The results thus lead us to conclude that in order to achieve best effects of chelation therapy, co-administration of zinc with chelator might be preferred. However, detailed experimental studies with variable doses and after chronic arsenic exposure are required. PMID:21783469

Modi, Manoj; Pathak, Uma; Kalia, Kiran; Flora, S J S

2005-01-01

324

Animal models to study aetiopathology of epilepsy: what are the features to model?  

PubMed

In order to understand the physiopathology of epilepsies and develop antiepileptic drugs, animal models have been developed. These models appear to be valuable predictors of treatment efficacy; however, several of the currently used models remain questionable and probably inappropriate for the search for new treatments, in particular for epilepsies that cannot be treated by current antiepileptic drugs. In the present review, we report the results of a recent survey conducted by neurologists in charge of an epilepsy programme based at different hospitals in France. The 36 experts were questioned, via the internet, on the most critical features of four prototypic forms of epilepsy (idiopathic generalised epilepsies with convulsive seizures, absence epilepsy, focal epilepsy associated with dysplasia, and focal epilepsy associated with hippocampal sclerosis) that should be taken into account with regards to the relevance of animal models of epilepsy. Their answers suggest that most current models for focal epilepsies associated with either dysplasia or hippocampal sclerosis do not address the most relevant features. The models currently used in mice and rats are discussed in light of the data obtained in our survey. PMID:22947423

Guillemain, Isabelle; Kahane, Philippe; Depaulis, Antoine

2012-09-01

325

Drug administration in animal studies of cardiac arrest does not reflect human clinical experience  

PubMed Central

Introduction To date, there is no evidence showing a benefit from any advanced cardiac life support (ACLS) medication in out-of-hospital cardiac arrest (OOHCA), despite animal data to the contrary. One explanation may be a difference in the time to first drug administration. Our previous work has shown the mean time to first drug administration in clinical trials is 19.4 minutes. We hypothesized that the average time to drug administration in large animal experiments occurs earlier than in OOHCA clinical trials. Methods We conducted a literature review between 1990 and 2006 in MEDLINE using the following MeSH headings: swine, dogs, resuscitation, heart arrest, EMS, EMT, ambulance, ventricular fibrillation, drug therapy, epinephrine, vasopressin, amiodarone, lidocaine, magnesium, and sodium bicarbonate. We reviewed the abstracts of 331 studies and 197 full manuscripts. Exclusion criteria included: non-peer reviewed, all without primary animal data, and traumatic models. From these, we identified 119 papers that contained unique information on time to medication administration. The data are reported as mean, ranges, and 95% confidence intervals. Mean time to first drug administration in animal laboratory studies and clinical trials was compared with a t-test. Regression analysis was performed to determine if time to drug predicted ROSC. Results Mean time to first drug administration in 2378 animals was 9.5 minutes (range 3.0–28.0; 95% CI around mean 2.78, 16.22). This is less than the time reported in clinical trials (19.4 min, p<0.001). Time to drug predicted ROSC (Odds Ratio 0.844; 95% CI 0.738, 0.966). Conclusion Shorter drug delivery time in animal models of cardiac arrest may be one reason for the failure of animal studies to translate successfully into the clinical arena.

Reynolds, Joshua C.; Rittenberger, Jon C.; Menegazzi, James J.

2007-01-01

326

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

327

Ultrastructural Studies of Effects of Streptozotocin-Temporal Study in Mice.  

National Technical Information Service (NTIS)

A study was made of the ultrastructural changes occurring in the islets of Langerhans of mice sacrificed one, three, five, seven, nine, and 24 hours after intravenous administration of a single dose of Streptozotocin at 200 mg/kg. Within one hour after co...

M. L. Vernon T. W. Tusing P. Schein E. R. Homan D. P. Rall

1967-01-01

328

Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report  

SciTech Connect

Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O 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 and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

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

1988-08-01

329

The Relationship Between Domestic Violence and Animal AbuseAn Australian Study  

Microsoft Academic Search

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 community took part in the study. Significantly

Anne M. Volant; Judy A. Johnson; Eleonora Gullone; Grahame J. Coleman

2008-01-01

330

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...

331

WWW design code – a new tool for colour estimation in animal studies  

Microsoft Academic Search

BACKGROUND: The colour of animals' skin, fur, feathers or cuticula has been estimated in a large number of studies. The methods used to do so are diverse, with some being costly and not available to all researchers. In a study to measure plumage colour in a bird species, a new method of creating a colour chart was developed. While colour-charts

Åsa Berggren; Juha Merilä

2004-01-01

332

Histochemical similarities between human and animal globoid cells in Krabbe's disease: a lectin study  

Microsoft Academic Search

Lectin-histochemical studies were performed on paraffin-embedded brain tissue sections to identify the specific sugar residues of undegraded “stored” substances in the cytoplasm of globoid cells from patients with globoid cell leukodystrophy. We studied brain tissues from six human patients with galactosylceramide lipidosis (i. e., Krabbe's disease) and compared them to brain tissues from animals with a similar enzyme deficiency including

J. Alroy; A. A. Ucci; V. Goyal; A. Aurilio

1986-01-01

333

Animal-assisted therapy for persons with aphasia: A pilot study  

Microsoft Academic Search

This study explored the effects and effectiveness of animal-assisted therapy (AAT) for persons with aphasia. Three men with aphasia from left-hemisphere strokes participated in this study. The men received one semester of traditional ther- apy followed by one semester of AAT. While both therapies were effective, in that each participant met his goals, no significant differences existed between test results

Beth L. Macauley

2006-01-01

334

Animal models of osteoarthritis.  

PubMed

Animal models of osteoarthritis are used to study the pathogenesis of cartilage degeneration and to evaluate potential antiarthritic drugs for clinical use. Animal models of naturally occurring osteoarthritis (OA) occur in knee joints of guinea pigs, mice and other laboratory animal species. Transgenic models have been developed in mice. Commonly utilized surgical instability models include medial meniscal tear in guinea pigs and rats, medial or lateral partial meniscectomy in rabbits, medial partial or total meniscectomy or anterior cruciate transection in dogs. Additional models of cartilage degeneration can be induced by intra-articular iodoacetate injection or by administration of oral or parenteral quinolone antibiotics. None of these models have a proven track record of predicting efficacy in human disease since there are no agents that have been proven to provide anything other than symptomatic relief in human OA. However, agents that are active in these models are currently in clinical trials. Methodologies, gross and histopathologic features and comparisons to human disease will be discussed for the various models. PMID:15758487

Bendele, A M

2001-06-01

335

78 FR 63477 - Guidance for Industry on Active Controls in Studies To Demonstrate Effectiveness of a New Animal...  

Federal Register 2010, 2011, 2012, 2013

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry 204 entitled ``Active Controls in Studies to Demonstrate Effectiveness of a New Animal Drug for Use in Companion Animals.'' This guidance advises industry on the use of active controls in studies intended to provide substantial evidence of effectiveness of new animal drugs for use in......

2013-10-24

336

Novel method for studying postoperative ileus in mice  

PubMed Central

Introduction: Postoperative ileus (POI) is characterized by a transient inhibition of coordinated motility of the gastrointestinal (GI) tract after abdominal surgery and leads to increased morbidity and prolonged hospitalization. Currently, intestinal manipulation of the intestine is widely used as a preclinical model of POI. The technique used to manipulate the intestine is however highly variable and difficult to standardize, leading to large variations and inconsistent findings between different investigators. Therefore, we developed a device by which a fixed and adjustable pressure can be applied during intestinal manipulation. Methods: The standardized pressure manipulation method was developed using the purpose-designed device. First, the effect of graded manipulation was examined on postoperative GI transit. Next, this new technique was compared to the conventional manipulation technique used in previous studies. GI transit was measured by evaluating the intestinal distribution of orally gavaged fluorescein isothiocyanate (FITC)-labeled dextran. Infiltration of myeloperoxidase positive cells and cytokine production (ELISA) in the muscularis externa of the intestine were assessed. Results: Increasing pressures resulted in a graded reduction of intestinal transit and was associated with intestinal inflammation as demonstrated by influx of leukocytes and increased levels of IL-6, IL-1? and MCP-1 compared to control mice. With an applied pressure of 9 grams a similar delay in intestinal transit could be obtained with a smaller standard deviation, leading to a reduced intra-individual variation. Conclusions: This method provides a reproducible model with small variation to study the pathophysiology of POI and to evaluate new anti-inflammatory strategies.

van Bree, Sjoerd HW; Nemethova, Andrea; van Bovenkamp, Fleur S; Gomez-Pinilla, Pedro; Elbers, L; Giovangiulio, Martina Di; Matteoli, Gianluca; van Vliet, Jan; Cailotto, Cathy; Tanck, Michael WT; Boeckxstaens, Guy EE

2012-01-01

337

Targeted gene mutation approaches to the study of anxiety-like behavior in mice  

Microsoft Academic Search

Studying the behavioral phenotypes of transgenic and gene knockout mice is a powerful means to better understand the pathophysiology of neuropsychiatric disorders and ultimately improve their treatment. This paper provides an overview of the methods and findings of studies that have tested for anxiety-related behavioral phenotypes in gene mutant mice. In the context of improving the side effect burden of

Andrew Holmes

2001-01-01

338

Conditional knockout mice to study alternative splicing in vivo.  

PubMed

Analysis of genomes has revealed that the total number of human genes is comparable to those of simpler organisms, and thus, the number of genes does not correlate with the complexity and functional diversity of different organisms. Multiple mechanisms, including alternative splicing, are believed to contribute to the molecular complexity in higher eukaryotes. Given the fact that more than half of human genes undergo alternative splicing, however, little is known about the biological relevance of most alternative splicing events and their regulatory mechanisms. Recent work has highlighted the power of reverse genetic approaches in addressing regulated splicing in animal models. Here, we focus on the conditional knockout approach adapted for splicing research with the intention to provide a general guide to the generation of mouse models to study regulated splicing in development and disease. PMID:16314268

Xu, Xiangdong; Fu, Xiang-Dong

2005-12-01

339

Effect of Genistein on Immune Responses in NC\\/Nga Mice Used as an Animal Model for Atopic Dermatitis  

Microsoft Academic Search

The isoflavone genistein is a phytoestrogen found in high levels in soy products that has been associated with decreased incidence of breast and prostate cancers. In addition, a recent clinical trial suggests that supplementation with the dietary genistein may be as effective as hormone replacement therapy in attenuating menopause-related bone loss without causing the associated side effects. In this study,

Tohru SAKAI; Mari KOGISO; Kaori MITSUYA; Shigeru YAMAMOTO

2004-01-01

340

Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis.  

PubMed

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. PMID:23836817

De Clercq, Evelien; Kalmar, Isabelle; Vanrompay, Daisy

2013-07-08

341

Genetic contributions to myopic refractive error: Insights from human studies and supporting evidence from animal models.  

PubMed

Genetic studies of both population-based and recruited affected patient cohorts have identified a number of genomic regions and candidate genes that may contribute to myopic development. Scientists have developed animal models of myopia, as collection of affected tissues from patents is impractical. Recent advances in whole exome sequencing technology show promise for further elucidation of disease causing variants as in the recent identification of rare variants within ZNF644 segregating with pathological myopia. We present a review of the current research trends and findings on genetic contributions to myopic refraction including candidate loci for myopic development and their genomic convergence with expression studies of animal models inducing myopic development. PMID:23379998

Hawthorne, Felicia A; Young, Terri L

2013-02-01

342

Studies of an expanded trinucleotide repeat in transgenic mice  

SciTech Connect

Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

Bingham, P.; Wang, S.; Merry, D. [Univ. of Pennsylvania, Philadelphia, PA (United States)

1994-09-01

343

Toxicology studies of a chemical mixture of 25 groundwater contaminants. II. Immunosuppression in B6C3F1 mice  

SciTech Connect

Concern over the potential adverse health effects of chemically contaminated groundwater has existed for many years. In general, these studies have focused on retrospective epidemiological studies for cancer risk. In the present studies, immune function was monitored in female B6C3F1 mice exposed to a chemical mixture in drinking water for either 14 or 90 days. The mixture consisted of 25 common groundwater contaminants frequently found near toxic waste dumps, as determined by EPA surveys. None of the animals developed overt signs of toxicity such as body or liver weight changes. Mice exposed to the highest dose of this mixture for 14 or 90 days showed immune function changes which could be related to rapidly proliferating cells, including suppression of hematopoietic stem cells and of antigen-induced antibody-forming cells. Some of these responses, e.g., granulocyte-macrophage colony formation, were also suppressed at lower concentrations of the chemical mixture. There were no effects on T cell function or T and B cell numbers in any of the treatment groups. Altered resistance to challenge with an infectious agent also occurred in mice given the highest concentration, which correlated with the immune function changes. Paired-water studies indicated that the immune effects were related to chemical exposure and not to decreased water intake. These results suggest that long-term exposure to contaminated groundwater may represent a risk to the immune system in humans.

Germolec, D.R.; Yang, R.S.; Ackermann, M.F.; Rosenthal, G.J.; Boorman, G.A.; Blair, P.; Luster, M.I. (National Institutes of Environmental Health Sciences, Research Triangle Park, NC (USA))

1989-10-01

344

The Impact of Animation on Visual Search Tasks in a Web Environment: A Multi-Year Study  

Microsoft Academic Search

Research results from a previous study show that animation as non-primary information significantly reduces information-seeking performance in a web-based environment (Zhang, 1999, 2000). Furthermore, in a different study, Zhang (2001) finds that animation on the left side of a screen has a higher negative impact on task performance than animation on the right side; animation also has different impact on

Ping Zhang; Nelson Massad

2003-01-01

345

EXPERIMENTAL ANIMAL MAINTENANCE  

DOEpatents

A method of housing experimental animals such as mice in individual tube- like plastic enclosures is described. Contrary to experience, when this was tried with metal the mice did not become panicky. Group housing, with its attendant difficulties, may thus be dispensed with. (AEC)

Finkel, M.P.

1962-01-22

346

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

347

The effect of music on cognitive performance: insight from neurobiological and animal studies.  

PubMed

The past 50 years have seen numerous claims that music exposure enhances human cognitive performance. Critical evaluation of studies across a variety of contexts, however, reveals important methodological weaknesses. The current article argues that an interdisciplinary approach is required to advance this research. A case is made for the use of appropriate animal models to avoid many confounds associated with human music research. Although such research has validity limitations for humans, reductionist methodology enables a more controlled exploration of music's elementary effects. This article also explores candidate mechanisms for this putative effect. A review of neurobiological evidence from human and comparative animal studies confirms that musical stimuli modify autonomic and neurochemical arousal indices, and may also modify synaptic plasticity. It is proposed that understanding how music affects animals provides a valuable conjunct to human research and may be vital in uncovering how music might be used to enhance cognitive performance. PMID:16585799

Rickard, Nikki S; Toukhsati, Samia R; Field, Simone E

2005-12-01

348

Heterotopic bone formation around vessels: pilot study of a new animal model.  

PubMed

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; Zwahlen, Roger A

2013-08-01

349

A reconsideration of the relevance of recent animal studies for development of treatment procedures for alcoholics.  

PubMed

Amit and Sutherland's conclusions concerning the use of conditioned taste aversions for alcoholism treatment are critically evaluated. Their conclusion that painful electric shock is contraindicated as a basis for alcohol taste aversions is consistent with the animal and human literature which depicts nausea as a more biologically appropriate US for taste aversion formation. However, Amit and Sutherland also conclude that alcoholics will not develop illness-induced alcohol aversions because animal studies show that aversion acquisition is disrupted by preconditioning familiarity with the conditioned stimulus (CS) - flavor - or unconditioned stimulus (US) - illness. This conclusion is untenable because Amit and Sutherland only considered animal conditioning methods that differed markedly from aversion therapy practices. Other animal studies modeled after aversion therapy procedures clearly show CS and US preexposure effects to be transitory phenomena. Moreover, experimental and clinical data show humans to be quite susceptible to taste aversion formation, and that many alcoholics do form strong alcohol aversions under appropriate conditioning parameters. Additional implications of the animal literature for effective aversion therapy are explored, and the paper concludes with a discussion of covert sensitization, a promising verbal aversion therapy which has resulted in the development of strong alcohol aversions in many volunteer subjects at the Augusta Veterans Administration Medical Center. PMID:7188741

Elkins, R L

1980-02-01

350

Chemical and pharmacological studies of Phyllanthus caroliniensis in mice.  

PubMed

The aim of this study was to isolate and characterize the constituents of the hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis, and also to evaluate the preliminary antinociceptive action of the HE and purified compounds in mice. Phytosterols, quercetin, gallic acid ethyl ester and geraniin were identified in P. caroliniensis on the basis of 1H and 13C NMR spectral data and by mixed co-TLC and co-HPLC injection with authentic samples. The HE of P. caroliniensis (10-100 mg kg-1, i.p.) inhibited, in a dose-related manner, acetic acid-induced abdominal constrictions in mice, with a mean ID50 value of 23.7 mg kg-1. In the formalin test, the HE given intraperitoneally (1-30 mg kg-1) or orally (25-600 mg kg-1) caused graded inhibitions of both the neurogenic (first phase) and the inflammatory response (late phase) of formalin-induced licking. The HE was 54-fold more effective in inhibiting the late phase than it was in inhibiting the first phase of the formalin test, with mean ID50 values of 3.6 and 196.4 mg kg-1, respectively. The HE failed, however, to affect the oedematogenic response associated with the late phase of formalin-induced pain. In addition, the reference drug, aspirin, given intraperitoneally (1-100 mg kg-1) or orally (100-600 mg kg-1), caused significant inhibition of the late but not the first phase of the formalin test. Pharmacological analysis also revealed that quercetin, gallic acid ethyl ester and a semi-purified fraction of flavonoids (1-100 mg kg-1, i.p.) exhibited graded and significant antinociception against acetic acid-induced abdominal constriction. The mean ID50 values (mg kg-1) for these effects were: 18.8, 34.7 and 5.3, respectively. It is concluded that quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might account for the antinociceptive action reported for the HE of P. caroliniensis. PMID:9004183

Cechinel Filho, V; Santos, A R; De Campos, R O; Miguel, O G; Yunes, R A; Ferrari, F; Messana, I; Calixto, J B

1996-12-01

351

Carcinogenesis related to intense pulsed light and UV exposure: an experimental animal study  

Microsoft Academic Search

This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three IPL treatments at 2-week intervals. Simulated solar radiation was administered preoperatively [six standard erythema doses (SED) four times weekly for 11 weeks] as

L. Hedelund; C. Lerche; H. C. Wulf; M. Haedersdal

2006-01-01

352

Development of a K-edge micro CT for the study of tumor angiogenesis in small animals  

NASA Astrophysics Data System (ADS)

A new micro scanner CT for small animals - based on a couple of parallel quasi-monochromatic X-ray beams with different energies selectable - is under development. The aim of the study is the in vivo imaging of the tumor neo-angiogenesis pattern in an earlier diagnostic phase and the analysis of cancer growth and metastasis development in different tumor types on mice. As previously demonstrated1, the imaging system based on dual energy quasi- monochromatic X-ray beams provides higher sensitivity in detecting low concentrations of iodine contrast medium if compared to traditional polychromatic X-ray equipment. The K-edge dual energy radiology is a realistic candidate to recognize tumor neo- angiogenesis process in a very earlier stage, in which conventional systems are very poor in sensitivity. Moreover, the capability to select the energy of quasi-monochromatic beams enables the use of the Multi-Energy Quasi-Monochromatic technique. Tuning properly the energies allows maximizing the difference between linear absorption coefficients of healthy and pathological tissues increasing the contrast of pathologies. In order to optimize the contrast with this technique, one should know the X-ray energy regions where the absorption of healthy and pathological tissues eventually differs and that for each type of tumor under study. For this reason, the systematic X-ray characterization of many types of healthy and neoplastic human and mice tissues is in progress. The goal of this work is to obtain a catalog of liner attenuation coefficients of a variety of pathological tissues for respect to the healthy ones, finding any energy windows of radiological differentiation. In this paper, the theoretical methods are presented with development works and preliminary results.

Baldazzi, G.; Bollini, D.; Gambaccini, M.; Golfieri, R.; Lollini, P. L.; Margotti, A.; Masetti, S.; Nicoletti, G.; Pancaldi, G.; Roma, L.; Rossi, P. L.; Zuffa, M.

2006-03-01

353

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

354

Animal models of orthopoxvirus infection.  

PubMed

Smallpox was one of the most devastating diseases known to humanity. Although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either Variola virus (VARV), the causative agent of smallpox, or another species of Orthopoxvirus could be used as agents of bioterrorism. Therefore, development of countermeasures to Orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various animal models. Smallpox typically presented as a generalized pustular rash with 30 to 40% mortality, and although smallpox-like syndromes can be induced in cynomolgus macaques with VARV, research with this virus is highly restricted; therefore, animal models with other orthopoxviruses have been investigated. Monkeypox virus causes a generalized vesiculopustular rash in rhesus and cynomolgus macaques and induces fatal systemic disease in several rodent species. Ectromelia virus has been extensively studied in mice as a model of orthopoxviral infection in its natural host. Intranasal inoculation of mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus causes pneumonia and fatal systemic infections in rabbits and can be naturally transmitted between rabbits by an aerosol route similar to that of VARV in humans. No single animal model recapitulates all known aspects of human Orthopoxvirus infections, and each model has its advantages and disadvantages. This article provides a brief review of the Orthopoxvirus diseases of humans and the key pathologic features of animal models of Orthopoxvirus infections. PMID:20682806

Chapman, J L; Nichols, D K; Martinez, M J; Raymond, J W

2010-08-03

355

Summary and meta-analysis of prospective studies of animal fat intake and breast cancer.  

PubMed

The objective of the present review was to examine the potential association between animal fat intake and breast cancer. We conducted a meta-analysis and review of epidemiological cohort studies, including data reported in the Pooling Project publication of Prospective Studies of Diet and Cancer. Random- and fixed-effects models were utilised to generate summary relative risk estimates (SRRE), and sensitivity and influence analyses were conducted. In the meta-analysis that included data reported in the Pooling Project publication of prospective cohorts (n 8) and subsequent publications of cohort studies (n 3), no significant association was observed comparing the highest category of animal fat intake with the lowest (SRRE 1.03; 95 % CI: 0.76, 1.40). Similarly, no significant association between a 5 % increment of energy from animal fat intake and breast cancer (SRRE 1.02; 95 % CI 0.97, 1.07) was observed in the meta-analysis of these studies. In conclusion, the results of the present quantitative assessment are not supportive of a positive independent association between consumption of animal fat and breast cancer, although findings may be sensitive to the type of dietary instrument used in cohort studies. PMID:20181297

Alexander, Dominik D; Morimoto, Libby M; Mink, Pamela J; Lowe, Kimberly A

2010-02-25

356

[Study on recent status of development of genetically modified animals developed not for food purposes].  

PubMed

Genetically modified (GM) animals can be classified into two groups, those developed for food purposes and those developed not for food purposes. We investigated the recent status of development of GM animals developed not for food purposes. Among the GM animals developed not for food purposes, GM fish, chickens, and pigs were selected because many articles have been published on these organisms. Relevant articles published between 2008 and 2011 were surveyed using PubMed and transgenic fish, chicken, or pig as keywords. Then, studies on organisms that could potentially contaminate the food chain with products from these GM animals were selected and analyzed. Fifteen articles on GM fish were found. These articles were classified into four categories: bioreactor (n = 4), resistance to microorganisms (n = 6), resistance to environmental stresses (n = 1), and detection of chemicals (n = 4). Zebrafish were used in 8 of the articles. Six, three, and three articles were reported from Taiwan, Canada and China. Seven articles on GM chickens were found. These articles were classified into two categories: bioreactor (n = 5), and resistance to pathogens (n = 2). Two articles were reported from Japan and Korea, each. As for GM pigs, 43 articles were found. These articles were classified into three categories: xenotransplantation (n = 36), bioreactor (n = 6), and environmental cleanup (n = 1). Nineteen, seven, six, and five articles were reported from USA, Germany, Korea and Taiwan, respectively. Understanding the recent development of GM animals produced not for food purpose is important for assuring the safety of food. PMID:23243988

Nakajima, Osamu; Akiyama, Hiroshi; Teshima, Reiko

2012-01-01

357

STUDIES ON THE RUNTING SYNDROME IN NEWBORN MICE  

PubMed Central

Runting was produced by homologous spleen or lymph node cell suspensions, but not by isologous spleen or homologous liver or kidney cell suspensions. The incidence of runting (a) varied with the particular strain combination employed, (b) increased with increased dose of foreign cells, and (c) decreased as the time interval between birth and inoculation with foreign cells was increased. A focal, coagulative necrotic, liver lesion was described in runted mice. It was found that viable cells were required to produce the runting syndrome. Frozen-thawed cells, homogenized cells, and the cell-free supernatant of ground spleen suspensions failed to produce runting. Runted mice were found to have an anemia of variable degree, and white blood cell counts ranging from marked leukopenia to severe leucocytosis. Mice receiving isologous spleen or homologous liver or kidney showed normal red and white blood cell counts. Isologous spleen cells, given to newborn mice within 30 minutes following injection of homologous spleen cells, conferred significant protection against the runting syndrome. Isologous spleen injected 1 day after the injection of homologous spleen failed to protect. Newborn mice which had received homologous spleen cells were protected from becoming runted by treatment with "anti-cell donor strain" serum. The offspring of mothers which had been immunized against the spleen cell donor's strain failed to become runted when treated with homologous spleen cells. The data are regarded as compatible with the concept, presented by previous workers, that runting is the result of an immunological reaction of foreign cells against a tolerant host.

Siskind, Gregory W.; Thomas, Lewis

1959-01-01

358

Prompt-gamma neutron activation analysis facility for in vivo body composition studies in small animals.  

PubMed

The design, calibration, dosimetry and performance evaluation of a prompt-gamma neutron activation analysis facility for in vivo body composition studies in small animals (i.e. rats or rabbits) is discussed. The system design was guided by Monte Carlo transport calculations using MCNP-4C code. A system was built and performance evaluation was made using a 185-GBq Pu-Be neutron source. Prompt-gamma rays produced by neutron capture reactions were detected by a combination of a NaI(Tl) scintillation and a HPGe semiconductor detectors. Nitrogen and chlorine were quantified by analysis of the 10.83-MeV and 6.11-MeV peaks, respectively. Appropriate corrections for the animal body size were determined. The facility described allows the in vivo determination of protein and extracellular space in sets of experimental animals. PMID:14762643

Stamatelatos, I E; Kasviki, K; Green, S; Gainey, M; Kalef-Ezra, J; Beddoe, A

2004-02-05

359

Optical oxygen microrespirometry as a platform for environmental toxicology and animal model studies.  

PubMed

We present a new methodology for testing physiological responses of small organisms (size 70-500 microm) via changes in their oxygen respiration monitored by quenched-phosphorescence oxygen sensing on a scale of a single organism. The method is demonstrated using three different formats of respirometric assays, Artemia salina and mouse embryos as model animals, and various effectors including compounds that induce and prevent superoxide-mediated and heavy metal ion toxicity. These assays, which employ soluble oxygen probes, standard fluorescent readers, and accessorytools, provide sensitive, noninvasive, real-time monitoring of animal respiration, and rapid assessment of EC50, sublethal effects, and metabolic alterations. Applications include screening for acute toxicity of compound libraries and environmental samples, and the study of animal physiology and metabolism. PMID:16053104

O'Mahony, Fiach C; O'Donovan, Ciara; Hynes, James; Moore, Tom; Davenport, John; Papkovsky, Dmitri B

2005-07-01

360

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

361

Brain microdialysis and its application for the study of animal behaviour  

Microsoft Academic Search

Microdialysis is a sampling method that is used to determine the extracellular concentration of neurotransmitters in the brain. The method can be applied to conscious and unrestrained animals and is very suitable for the study of the chemistry of endogenous behaviour. This article reviews the contribution that microdialysis made to our understanding of the chemistry of behaviour. Methodological and practical

Ben H. C. Westerink

1995-01-01

362

Evaluation of Drosophila melanogaster as an alternative animal for studying the neurotoxicity of heavy metals  

Microsoft Academic Search

Heavy metals cause irreversible neurobehavioral damage in many developing mammals, but the mechanisms of this damage are unknown. The influence of three heavy metal compounds, triethyllead chloride, lead acetate and cadmium chloride, on lethality, development, behavior and learning was studied using the fruit fly,Drosophila melanogaster. This animal was used because it allows hundreds of subjects to be assayed very easily

Jonathan M. Akins; Joyce A. Schroeder; Danny L. Browert; H. Vasken Aposhian

1992-01-01

363

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

364

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

365

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

366

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…

Volant, Anne M.; Johnson, Judy A.; Gullone, Eleonora; Coleman, Grahame J.

2008-01-01

367

Results of animal studies suggest a nonlinear dose-response relationship for benzene effects  

Microsoft Academic Search

Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important. Animal data can offer indications about what could happen in humans and provide more diverse information than epidemiological data with respect to dose-response consideration. The authors have considered experiments investigating metabolism, short-term genotoxicity tests,

S. Parodi; M. Taningher; W. K. Lutz; A. Colacci; M. Mazzullo; S. Grilli

1989-01-01

368

Dynamic studies of small animals with a four-color diffuse optical tomography imager  

NASA Astrophysics Data System (ADS)

We present newly developed instrumentation for full-tomographic four-wavelength, continuous wave, diffuse optical tomography (DOT) imaging on small animals. A small-animal imaging stage was constructed, from materials compatible with in-magnet studies, which offers stereotaxic fixation of the animal and precise, stable probe positioning. Instrument performance, based on calibration and phantom studies, demonstrates excellent long-term signal stability. DOT measurements of the functional rat brain response to electric paw stimulation are presented, and these demonstrate high data quality and excellent sensitivity to hemodynamic changes. A general linear model analysis on individual trials is used to localize and quantify the occurrence of functional behavior associated with the different hemoglobin state responses. Statistical evaluation of outcomes of individual trials is employed to identify significant regional response variations for different stimulation sites. Image results reveal a diffuse cortical response and a strong reaction of the thalamus, both indicative of activation of pain pathways by the stimulation. In addition, a weaker lateralized functional component is observed in the brain response, suggesting presence of motor activation. An important outcome of the experiment is that it shows that reactions to individual provocations can be monitored, without having to resort to signal averaging. Thus the described technology may be useful for studies of long-term trends in hemodynamic response, as would occur, for example, in behavioral studies involving freely moving animals.

Schmitz, Christoph H.; Graber, Harry L.; Pei, Yaling; Farber, Mark; Stewart, Mark; Levina, Rita D.; Levin, Mikhail B.; Xu, Yong; Barbour, Randall L.

2005-09-01

369

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

370

Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives  

Microsoft Academic Search

Nicotine dependence is a disease of constantly growing importance. This mini-review describes the effects of nicotine in humans and focuses on the various laboratory animal models developed to study the dependence-related behavioral effects of nicotine. In ad- dition, we outline the current therapeutic approaches designed to substitute nicotine from cigarette smoke with safer compounds or to relieve symptoms of nicotine

Magdalena Zaniewska

371

STUDIES ON MORPHOLOGY OF ECHINOCOCCUS GRANULOSUS FROM DIFFERENT ANIMAL-DOG ORIGIN  

Microsoft Academic Search

Morphological studies on larval and adult Echinococcus granutosus of buffalo, cattle, sheep, goats and camel origin revealed non-significant difference as regards the total number of hooks as well as shape and arrangement of the hooks. The mean total length of large and small hooks did not vary significantly in protoscoleces from different animal origin but mean total length of large

ALTAF HUSSAIN; AZHAR MAQBOOL; AKHTAR TANVEER; AWAIS ANEES

2005-01-01

372

A new approach to analysis of RF ultrasound echo signals for tissue characterization: animal studies  

Microsoft Academic Search

We present the results of an animal tissue characterization study to demonstrate the effectiveness of a novel approach in collecting and analyzing ultrasound echo signals. In this approach, we continuously record RF echo signals backscattered from a tissue sample, while the imaging probe and the tissue are fixed in position. The continuously recorded RF data generates a time series of

Mehdi Moradi; Parvin Mousavi; Philip A. Isotalo; David R. Siemens; Eric E. Sauerbrei; Purang Abolmaesumi

2007-01-01

373

Techniques for the study of learning in animals: Analysis and classification  

Microsoft Academic Search

Present classifications of techniques for the study of animal learning are inadequate. The proposed classification is developed in terms of the functional significance of differences in technique. Thus 2 techniques differ if they yield results which differ in some fundamental respect but may be considered interchangeable if they produce similar results. The 3 major classifications are: Thorndikian Situations, Pavlovian Situations,

M. E. Bitterman

1962-01-01

374

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

375

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

376

Endometriosis research: animal models for the study of a complex disease  

Microsoft Academic Search

Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence

Irene Tirado-González; Gabriela Barrientos; Nadja Tariverdian; Petra C. Arck; Mariana G. García; Burghard F. Klapp; Sandra M. Blois

2010-01-01

377

Radiolabelled mass-balance excretion and metabolism studies in laboratory animals: are they still necessary?  

PubMed

The conduct of excretion and metabolism studies using radiolabelled drugs in multiple laboratory animal species has been a mainstay of the suite of support activities provided by drug metabolism groups within pharmaceutical research and development organizations for decades. Drug metabolism scientists carry out exhaustive analyses of plasma and excretory matrices to comprehensively determine the profiles of metabolites in these species. While these analyses have taught us considerably regarding principles of drug metabolism and excretion, it is our contention that the routine conduct of such studies for every new drug development compound in every laboratory animal species used in toxicology studies is no longer necessary. The recently released regulatory guidance regarding metabolites and safety testing have better defined what we need to know regarding metabolite profiles in humans relative to animals. In this commentary, we propose a strategy wherein a radiolabel metabolism study is conducted only in humans, and that these data are utilized as a springboard to direct the exploration of steady-state human versus animal metabolite exposures. Such a strategy better serves the purpose of what is needed to support our understanding of the safety of a new drug candidate. Valuable expertise in drug metabolism and biotransformation can be redeployed to meet the burgeoning needs in drug design efforts to optimize structures with regard to metabolic clearance properties, understanding pharmacologically active metabolites, and reducing generation of chemically reactive metabolites. PMID:21992031

Obach, R Scott; Nedderman, Angus N; Smith, Dennis A

2011-10-12

378

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

379

Efficacy of topical benzydamine hydrochloride gel on oral mucosal ulcers: an in vivo animal study  

Microsoft Academic Search

The aim of this study was to investigate the effect of benzydamine hydrochloride bioadhesive gel on healing of oral mucosal ulceration in an animal model. For in vivo determination of the effects of the bioadhesive gel, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without active agent, the second group with the

B. Sezer; P. Güneri; A. Veral; H. Boyacio?lu; G. Ertan; J. B. Epstein

2011-01-01

380

CYTOGENETIC STUDIES IN MICE TREATED WITH THE JET FUELS, JET-A AND JP-8  

EPA Science Inventory

Cytogenetic studies in mice treated with the jet fuels, Jet-A and JP-8 Abstract The genotoxic potential of the jet fuels, Jet-A and JP-8, were examined in mice treated on the skin with a single dose of 240 ug/mouse. Peripheral blood smears were prepared at the start of the ...

381

The importance of appropriate controls, animal feed, and animal models in interpreting results from low-dose studies of bisphenol A  

Microsoft Academic Search

Interpreting results of studies that report only negative effects is problematic. A number of published studies to determine whether chemicals with estrogenic activity can cause effects at low doses have not taken into account the possibility that the commercial animal feed being used can mask effects of even potent estrogenic drugs such as diethylstilbestrol (DES). In addition, the sensitivity of

Frederick S. vom Saal; Catherine A. Richter; Rachel R. Ruhlen; Susan C. Nagel; Barry G. Timms; Wade V. Welshons

2005-01-01

382

Developmental impairments of select neurotransmitter systems in brains of Cln3(Deltaex7/8) knock-in mice, an animal model of juvenile neuronal ceroid lipofuscinosis.  

PubMed

The neuronal ceroidlipofuscinoses (NCL) are a group of neurodegenerative disorders and are the most common lysosomal storage diseases of infancy and childhood. Juvenile NCL is caused by CLN3 mutation, producing retinal degeneration, uncontrollable seizures, cognitive and motor decline, and early death before the age of 30 years. To study the pathogenetic mechanisms of the disease, Cln3 knock-in mice (Cln3(Deltaex7/8)) have been generated, which reproduce the 1.02-kb deletion in the CLN3 gene observed in more than 85% of juvenile NCL patients. To characterize the impact of the common Cln3 mutation on development of autofluorescent storage material, gliosis, glucose metabolism, oxidative stress, and transmitter receptors during postnatal brain maturation, brain tissue of Cln3(Deltaex7/8) mice at the ages of 3, 4, 5, 6, 9, and 19 months was subjected to immunocytochemistry to label gliotic markers and nitric oxide synthases; photometric assays to assess enzyme activities of glycolysis and antioxidative defense systems; and level of reactive nitrogen species as well as quantitative receptor autoradiography to detect select cholinergic, glutamatergic, and GABAergic receptor subtypes. The developmental increase in cerebral cortical autofluorescent lipofuscin-like deposition is accompanied by a significant astro- and microgliosis, increased activities of lactate dehydrogenase and phosphofructokinase, decreased level of glutathione peroxidase, enhanced amount of reactive nitrogen species, and lowered binding levels of N-methyl-D-aspartate- and M1-muscarinic acetylcholine receptors in select brain regions but hardly in GABA(A) receptor sites compared with wild-type mice. Detailed elucidation of the sequence of pathological events during postnatal development highlights new potential strategies for symptomatic treatment of the disease. PMID:18265413

Herrmann, Philipp; Druckrey-Fiskaaen, Caroline; Kouznetsova, Elena; Heinitz, Katrin; Bigl, Marina; Cotman, Susan L; Schliebs, Reinhard

2008-06-01

383

Studies of natural allele effects in mice can be used to identify genes causing common human obesity.  

PubMed

Although genes causing rare Mendelian forms of human obesity have provided much useful information about underlying causes of obesity, these genes do not explain significant proportions of common obesity. This review presents evidence that animal models can be used to uncover subtle genetic effects on obesity and can provide a powerful rigorous compliment to human association studies. We discuss the advantages of animal models of obesity, various approaches to discovering obesity genes, and the future of mapping and isolating naturally occurring alleles of obesity genes. We review evidence that it is important to map naturally occurring obesity genes using quantitative trait locus (QTL) mapping, instead of mutagenesis and knockout models because the latter do not allow study of interactions and because naturally occurring obesity alleles can interfere with cloning from mutagenesis projects. Because a substantial percentage of human obesity results from complex interactions, the underlying genes can only be identified by direct studies in humans, which are still very difficult, or by studies in mice that begin with QTL mapping. Finally, we emphasize that animal model studies can be used to prove that a specific gene, only associated with obesity in humans, can indeed be the underlying cause of obesity in mammals. PMID:14649375

Diament, A L; Fisler, J S; Warden, C H

2003-11-01

384

Studies on the anticonvulsant effect of U50488H on maximal electroshock seizure in mice.  

PubMed

The present study was designed to investigate the effect of U50488H, a prototype non-peptide kappa opioid agonist on convulsive behaviour using a maximal electroshock (MES) seizure test in mice. An attempt was also made to explore the role of possible receptors involved. MES seizures were induced via transauricular electrodes (60 mA, 0.2 s). Seizure severity was evaluated by means of two parameters, i.e., (1). duration of tonic hindlimb extensor phase and (2). mortality due to convulsions. Intraperitoneal (i.p.) administration of U50488H dose dependently (5-20 mg/kg) decreased the hindlimb extensor phase of MES. The anticonvulsant effect of U50488H was attenuated by the general opioid antagonist, naloxone at a high dose, and by MR2266, a selective kappa antagonist, but not by naltrindole, a delta antagonist. Coadministration of gamma-aminobutyric acid (GABA)ergic drugs (diazepam, GABA, muscimol, and baclofen) and the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK801), with U50488H augmented the anticonvulsant effect of the latter drug in mice. On the other hand, flumazenil, a central benzodiazepine (BZD) receptor antagonist, reversed the protective effect of diazepam and similarly, delta-aminovaleric acid (DAVA), a GABA(B) receptor antagonist, blocked the protective effect of baclofen, a GABA(B) agonist on the anti-MES action of U50488H. These BZD-GABAergic antagonists, namely, flumazenil or DAVA, on their own also counteracted the anti-electroshock seizure effect of U50488H given alone. However, mortality was not significantly altered in any of the above animal groups. Taken together, the findings have shown a possible role for multitude of important neurotransmitter systems, i.e., opioid (kappa), NMDA channel, GABA(A)-BZD-chloride channel complex, and GABA(B) receptors in the anticonvulsant action of U50488H. PMID:13679223

Manocha, Anshu; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

2003-08-01

385

Cytogenetic studies in mice treated with the jet fuels, Jet-A and JP-8.  

PubMed

The genotoxic potential of the jet fuels, Jet-A and JP-8, were examined in mice treated on the skin with a single dose of 240 mg/mouse. Peripheral blood smears were prepared at the start of the experiment (t = 0), and at 24, 48 and 72 h following treatment with jet fuels. Femoral bone marrow smears were made when all animals were sacrificed at 72 h. In both tissues, the extent of genotoxicity was determined from the incidence of micronuclei (MN) in polychromatic erythrocytes. The frequency of MN in the peripheral blood of mice treated with Jet-A and JP-8 increased over time and reached statistical significance at 72 h, as compared with concurrent control animals. The incidence of MN was also higher in bone marrow cells of mice exposed to Jet-A and JP-8 as compared with controls. Thus, at the dose tested, a small but significant genotoxic effect of jet fuels was observed in the blood and bone marrow cells of mice treated on the skin. PMID:15162067

Vijayalaxmi, V; Kligerman, A D; Prihoda, T J; Ullrich, S E

2004-01-01

386

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

387

Imaging the neural correlates of tinnitus: a comparison between animal models and human studies  

PubMed Central

Tinnitus is the perception of a sound, a so-called “phantom sound,” in the absence of a physical sound. The phantom perception persists after transection of the auditory nerve, indicating that the site of tinnitus manifestation is in the central nervous system. Imaging studies in tinnitus sufferers have revealed increased neuronal activity—hyperactivity—in subcortical and cortical auditory centers. These studies have demonstrated that non-auditory brain areas, such as the limbic system, are involved in the neural basis of tinnitus, Finally human imaging studies have led to novel hypotheses for the generation of tinnitus, such as the thalamocortical dysrhythmia hypothesis. Imaging in animal models of tinnitus exhibit similarities to results from human studies and have revealed hyperexcitability of auditory brain centers as a neural correlate of tinnitus. We propose that the comparison between animal model and human studies will aid in the design of appropriate experimental paradigms aimed at elucidating the cellular and circuit mechanisms underlying tinnitus.

Middleton, Jason W.; Tzounopoulos, Thanos

2012-01-01

388

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

389

Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.  

PubMed

The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(?M51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors). PMID:20808290

Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

2010-08-31

390

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.

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

2010-01-01

391

Performance evaluation of a mouse-sized camera for dynamic studies in small animals  

SciTech Connect

A mouse sized camera has been built in terms of collaboration between the presenting institutions. The system is used for the performance of dynamic studies in small animals, in order to evaluate novel radiopharmaceuticals. The active area of the detector is approximately 48?96 mm allowing depiction of the entire mouse in a single view. The system is based on two flat-panel Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMT), a pixellated NaI(Tl) scintillator and a copper?beryllium (CuBe) parallel-hole collimator. In this work, the evaluation results of the system are presented, using phantoms and small animals injected with conventional radiophrmaceuticals. Average resolution was ∼1.6 mm on the collimator surface and increased to ∼4.1 mm in 12 cm distance from the detector. The average energy resolution was measured and found to be ∼15.6% for Tc99m. Results from imaging thin capillaries demonstrated system's high resolution and sensitivity in activity variations was shown. Initial dynamic studies have been carried out in small animals injected with Tc99m-DTPA and Tc99m-MDP. The results show system's ability to perform kinetic imaging in small animals.

Loudos, George; Majewski, Stan; Wojcik, Randy; Weisenberger, Andrew G.; Sakellios, Nicolas; Nikita, Konstantina; Uzunglu, Nikolaus; Bouziotis, Penelope; Varvarigou, Alexandra

2007-02-01

392

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

PubMed

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, A M; Rudd, J A; Tattersall, F D; Aziz, Q; Andrews, P L R

2009-04-09

393

Development of an animal model to study the potential neurotoxic effects associated with welding fume inhalation.  

PubMed

Serious questions have been raised regarding a possible causal association between neurological effects in welders and the presence of manganese in welding fume. An experimental model is needed that could examine the potential neurotoxic effect of manganese after pulmonary exposure to welding fume. The National Institute for Occupational Safety and Health (NIOSH) has recently finished construction of a completely automated, computer controlled welding fume generation and inhalation exposure system for laboratory animals. The system is comprised of a programmable six-axis robotic welding arm and a water-cooled arc welding torch. A flexible trunk has been attached to the robotic arm of the welder and is used to collect and transport fume from the vicinity of the arc to the animal exposure chamber. Preliminary fume characterization studies have indicated that particle morphology, size, and chemical composition were comparable to welding fume generated in the workplace. Animal inhalation studies are currently underway. With the development of this novel system, an animal model has been established using controlled welding exposures to investigate the possible mechanisms by which welding fume may affect the central nervous system. PMID:16546258

Antonini, James M; O'Callaghan, James P; Miller, Diane B

2006-03-20

394

Implantation disturbance studies with linear alkylbenzene sulphonate in mice  

Microsoft Academic Search

Problems were evaluated in ICR mice concerning the implantation disturbance of linear alkylbenzene sulphonate (LAS). An experiment was made to determine the incidence of implantation disturbance, distribution in the body organs, and mutagenicity of LAS administered in early pregnancy. Approximately 14, 70, or 350 mg\\/kg of LAS was administered orally once on day 3 of gestation or once daily from

Naoko Koizumi; Ruriko Ninomiya; Yoshiki Inoue; Toshiyuki Tsukamoto; Masami Fujii; Yoshiko Yamamoto

1985-01-01

395

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...

396

STUDIES OF THE NEUROTOXICITY OF ORAL ARTEMISININ DERIVATIVES IN MICE  

Microsoft Academic Search

Intramuscular injections of high doses of the oil-soluble antimalarial artemisinin derivatives artemether and arteether produce an unusual pattern of selective damage to brain stem centers in experimental mammals, pre- dominantly those involved in auditory processing and vestibular reflexes. We have shown recently in adult Swiss albino mice that parenteral artesunate, a water-soluble derivative, is significantly less neurotoxic than intramuscular artemether

APICHART NONTPRASERT; SASITHON PUKRITTAYAKAMEE; MARIKA NOSTEN-BERTRAND; SIRIVAN VANIJANONTA; NICHOLAS J. WHITE

2000-01-01

397

Development of a high-sensitivity BGO well counter for small animal PET studies.  

PubMed

In quantitative measurements of small animal PET studies, blood sampling is limited due to the small amounts of blood such animals can provide. In addition, injection doses are quite limited. In this situation, a high-sensitivity well counter would be useful for reducing the amount of the blood sample needed from small animals. Bismuth germinate (BGO) has a high stopping power for high-energy gamma rays compared to NaI(Tl), which is commonly used for conventional well counters. We have developed a BGO well counter and have tested it for blood-sampling measurements in small animals. The BGO well counter uses a square BGO block (59 × 59 × 50 mm) with a square open space (27 × 27 × 34 mm) in the center of the block. The BGO block was optically coupled to a 59-mm square-shaped photomultiplier tube (PMT). Signals from the PMT were digitally processed for the integration and energy window setting. The results showed that the energy spectrum of the BGO well counter measured with a Na-22 point source provided counts that were about 6 times higher for a 1022-keV (511 keV × 2) gamma peak than the spectrum of a 2-in. NaI(Tl) well counter. The relative sensitivity of the developed BGO well counter was 3.4 times higher than that of a NaI(Tl) well counter. The time activity curve of arterial blood was obtained successfully with the BGO well counter for a F-18-FDG study on rat. The BGO well counter will contribute to reducing the amount of sampled blood and to improving the throughput of quantitative measurements in small animal PET studies. PMID:21987349

Yamamoto, Seiichi; Watabe, Hiroshi; Kanai, Yasukazu; Watabe, Tadashi; Imaizumi, Masao; Shimosegawa, Eku; Hatazawa, Jun

2011-10-11

398

Investigative study of radiopharmaceuticals useful for imaging skeletal muscle injury in experimental animals  

SciTech Connect

An experimental animal model for studying skeletal muscle injury is described. Tc-99m PYP is accumulated on the skeletal muscle injury, but its uptake on the adjacent bone obscures its usefulness in delineating the extent of the muscle injury. In-111 antimyosin accumulates and delineates the extent of the skeletal muscle injury and does not accumulate on the adjacent bone. Hence, In-111 antimyosin is a good radiopharmaceutical for studying the severity and prognosis of skeletal muscle injury.

Owunwanne, A.; Malki, A.; Sadek, S.; el-Gazzar, A.; Yacoub, T.; Abdel-Dayem, H.M. (Kuwait Univ., Safat)

1989-01-01

399

Histopathologic study of esophageal atresia and tracheoesophageal fistula in an animal model  

Microsoft Academic Search

A histopathologic study of tracheoesophageal anomalies was conducted on an Adriamycin-treated animal model to determine how closely it resembles the human pattern. Adriamycin was administered (2 mg\\/kg body weight) to timed-pregnant rats on days 6 through 9 of gestation. The fetuses were recovered at term, dissected and prepared for histological studies. Dissection showed a similar range of variants of tracheoesophageal

Jamal Merei; Christine Kotsios; John M. Hutson; Suzanne Hasthorpe

1997-01-01

400

Effect of ellagic acid on hepatic and pulmonary xenobiotic metabolism in mice: studies on the mechanism of its anticarcinogenic action.  

PubMed

Our recent studies have shown that ellagic acid, a naturally occurring dietary plant phenol, protects BALB/c mice against 3-methylcholanthrene-induced skin tumorigenesis. To further elucidate the mechanism of the antineoplastic action of ellagic acid its effect on hepatic and pulmonary benzo[a]pyrene (BP) metabolism, cytochrome P-450-dependent monooxygenases and glutathione S-transferase activities were studied in BALB/c mice. Chronic oral feeding of the compound in drinking water (0.3 mg/l for 16 weeks) or acute intraperitoneal administration (50 mg/kg for five consecutive days) of ellagic acid resulted in 20-25% decreases in hepatic and pulmonary cytochrome P-450 levels. Hepatic and pulmonary aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities in both groups of ellagic acid-treated animals were 33-52% and 28-43% lower than their respective non-ellagic acid-treated controls. Hepatic as well as pulmonary aminopyrine N-demethylase and epoxide hydrolase activities were unchanged in both groups of ellagic acid-treated mice. Hepatic glutathione S-transferase activity towards BP-4,5-oxide or 1-chloro-2,4-dinitrobenzene as substrates was found to be enhanced 51-79% and 38-58% in both groups of animals. H.p.l.c. analysis of organic solvent-soluble metabolites of BP by liver and lung microsomes indicated a substantial inhibition of diol formation (including BP-7,8-diol), as well as of phenols and quinones. In liver, these inhibitory effects were more pronounced after oral feeding than after intraperitoneal administration. Our results indicate that both acute and chronic administration of ellagic acid inhibits BP metabolism and/or enhances glutathione S-transferase activity. Thus the modulation of polycyclic aromatic hydrocarbon metabolism by ellagic acid may be related to the anticarcinogenic effects of this compound. PMID:3876174

Das, M; Bickers, D R; Mukhtar, H

1985-10-01

401

39-week carcinogenicity study with cyclosporin A in XPA-\\/- mice, wild type mice and XPA-\\/-.P53+\\/- double transgenic mice. Part of the ILSI\\/HESI Program on Alternative Methods for Carcinogenicity Testing  

Microsoft Academic Search

The objective of this study was to evaluate the carcinogenic response of\\u000acyclosporin A in XPA-\\/- mice having a C57BL\\/6 background. XPA-\\/- mice\\u000aare deficient in nucleotide excision repair and have shown increased\\u000asusceptibility to genotoxic carcinogens and uv-light. The study was part\\u000aof a world-wide evaluation program of alternative carcinogenicity assays,\\u000aincluding assays with transgenic mice, coordinated by the

Beems RB; Kreijl CF van; Steeg H van

2007-01-01

402

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

403

Results of a 90-day inhalation study of dicyclopentadiene in B6C3F1 mice.  

PubMed

The objective of this inhalation study was to determine and evaluate the potential toxic effects of dicyclopentadiene vapor in mice exposed for 13-weeks of repeated inhalation. Four groups, each consisting of 45 male and 45 female B6C3F1 mice, were exposed to dicyclopentadiene vapor by inhalation 6 h/day, 5 days/week, for 13 weeks (64 exposures) at targeted concentrations of 0, 1.0, 5.0, or 50 ppm. An assessment of toxicity is carried out after 2, 6, and 13 weeks of inhalation exposures. Additionally, animals were evaluated during the recovery period of 4 or 13 weeks after the last exposure. Observations and measurements to assess toxicity include clinical observations, body weight, organ weights, serum chemistry, and hematologic, ophthalmologic, gross pathologic, and histologic evaluations. The only systemic effects observed were a few statistically significant changes in organ weights; but these were considered spurious in nature. Ten male and nine female mice in the highest exposure group died during the study, while no more than two mice died in any other group. However, the excess mortality was without an apparent etiology or association to exposure and was attributed to pulmonary congestion as a consequence of pulmonary irritation. Under the conditions of this study, these data demonstrated that in the absence of overt systemic toxicity, respiratory congestion has the predominant effect at the exposure levels of 50 ppm. This observation contributes to the Globally Harmonized System harmonized hazard classification of Single Target Organ Toxicity - Single Exposure (H335, may cause respiratory irritation) for this substance. PMID:22933556

Kransler, Kevin M

2012-08-29

404

The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment  

PubMed Central

Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies.

2011-01-01

405

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

2012-11-29

406

Energy deficiency alters behaviours involved in transmission of Heligmosomoides polygyrus (Nematoda) in mice  

Microsoft Academic Search

Independent studies have shown that animal behaviour is affected by nutritional deficiency and that host be- haviour influences parasite transmission. The objectives of this study were to determine whether energy deficiency al- ters the behaviour profile of mice and the rate of exposure of mice to naturally acquired Heligmosomoides polygyrus (Nematoda) larvae. Outbred CF-1 and CD-1 female mice were fed

T. L. Heitman; K. G. Koski; M. E. Scott

2003-01-01

407

Animal models of candidiasis.  

PubMed

Animal models are powerful tools to study the pathogenesis of diverse types of candidiasis. Murine models are particularly attractive because of cost, ease of handling, technical feasibility, and experience with their use. In this chapter, we describe methods for two of the most popular murine models of disease caused by Candida albicans. In an intravenously disseminated candidiasis (DC) model, immunocompetent mice are infected by lateral tail vein injections of a C. albicans suspension. Endpoints include mortality, tissue burdens of infection (most importantly in the kidneys, although spleens and livers are sometimes also assessed), and histopathology of infected organs. In a model of oral/esophageal candidiasis, mice are immunosuppressed with cortisone acetate and inoculated in the oral cavities using swabs saturated with a C. albicans suspension. Since mice do not die from oral candidiasis in this model, endpoints are tissue burden of infection and histopathology. The DC and oral/esophageal models are most commonly used for studies of C. albicans virulence, in which the disease-causing ability of a mutant strain is compared with an isogenic parent strain. Nevertheless, the basic techniques we describe are also applicable to models adapted to investigate other aspects of pathogenesis, such as spatiotemporal patterns of gene expression, specific aspects of host immune response and assessment of antifungal agents, immunomodulatory strategies, and vaccines. PMID:19152040

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

2009-01-01

408

A COMPARATIVE ANATOMICAL STUDY OF THE HUMAN KNEE AND SIX ANIMAL SPECIES  

PubMed Central

Purpose Animal models are an indispensable tool for developing and testing new clinical applications regarding the treatment of acute injuries and chronic diseases of the knee joint. Therefore, the purpose of this study was to compare the anatomy of the intra-articular structures of the human knee to species commonly used in large animal research studies. Methods Fresh frozen cow (n=4), sheep (n=3), goat (n=4), dog (n=4), pig (n=5), rabbit (n=5), and human (n=4) cadaveric knees were used. Passive range of motion and intra-articular structure sizes of the knees were measured, the structure sizes normalized to the tibial plateau, and compared among the species. Results Statistically significant differences in the range of motion and intra-articular structure sizes were found among all the species. Only the human knee was able to attain full extension. After normalization, only the pig ACL was significantly longer than the human counterpart. The tibial insertion site of the ACL was split by the anterior lateral meniscus attachment in the cow, sheep, and pig knees. The sheep PCL had two distinct tibial insertion sites, while all the other knees had only one. Furthermore, only in human knees, both lateral meniscal attachments were located more centrally than the medial meniscal attachments. Conclusions/Clinical Relevance Despite the relatively preserved dimensions of the cruciate ligaments, menisci, and intercondylar notch amongst human and animals, structural differences in the cruciate ligament attachment sites and morphology of the menisci between humans and animals are important to consider when selecting an animal model.

Proffen, Benedikt L.; McElfresh, Megan; Fleming, Braden C.; Murray, Martha M.

2011-01-01

409

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

2007-08-23

410

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

411

A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw.  

PubMed

The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach. PMID:20202091

Biasotto, Matteo; Chiandussi, Silvia; Zacchigna, Serena; Moimas, Silvia; Dore, Franca; Pozzato, Gabriele; Cavalli, Fabio; Zanconati, Fabrizio; Contardo, Luca; Giacca, Mauro; Di Lenarda, Roberto

2010-02-28

412

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

413

Use of animal models in diagnosis and treatment of renal cell carcinoma  

Microsoft Academic Search

This paper gives an overview of animal models available for the study of human renal cell carcinoma. Animal model systems can be divided into four categories: drug-induced tumors, virus-induced tumors, spontaneous tumors and human tumors transplanted into nude mice. Animal models have been used for improvement of diagnostic and therapeutic procedures. New markers for the diagnosis of more aggressive tumors

R. J. A. van Moorselaar; J. A. Schalken; G. O. N. Oosterhof; F. M. J. Debruyne

1991-01-01

414

Re-Evaluate the Effect of Hyperbaric Oxygen Therapy in Cancer - A Preclinical Therapeutic Small Animal Model Study  

PubMed Central

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

Pande, Sneha; Sengupta, Amit; Srivastava, Anurag; Gude, Rajiv P.; Ingle, Arvind

2012-01-01

415

Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica in experimental animals.  

PubMed

This study was aimed to provide pharmacological basis for the medicinal use of Phyllanthus emblica fruit in indigestion and constipation using the in-vivo and in-vitro assays. The crude extract of the dried fruits of Phyllanthus emblica (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300?mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea-pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration-dependent and partially atropine-sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003-0.1?mg/mL) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003-1.0?mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that the Phyllanthus emblica possesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use of Phyllanthus emblica fruits in indigestion and constipation. PMID:22972571

Mehmood, Malik Hassan; Rehman, Abdul; Rehman, Najeeb-Ur; Gilani, Anwarul-Hassan

2012-09-12

416

Nutritional Role of Endosymbiotic Bacteria in Animal-Bacteria Symbioses: 'Solemya velum', a Case Study.  

National Technical Information Service (NTIS)

The nutritional role of endosymbiotic sulfur-oxidizing chemoautotrophic bacteria in animal-bacteria symbioses was investigated using the endosymbiont-containing protobranch clam, Solemya velum, as a general model of animal-bacteria symbioses. Animal-bacte...

N. M. Conway

1990-01-01

417

Study of DNA synthesis and mitotic activity of hepatocytes and its relation to angiogenesis in hepatectomised tumour bearing mice.  

PubMed

Partial hepatectomy (PH) alters serum concentrations of substances involved in cellular proliferation, leading to the compensatory liver hyperplasia. Furthermore, angiogenesis is mainly stimulated by vascular endothelial growth factor (VEGF) and is a fundamental requirement either in liver regeneration or in tumours growth. This study looks at the expression of VEGF, DNA synthesis (DNAs) and mitotic activity (MA