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Sample records for animal studies mice

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

    NASA Astrophysics Data System (ADS)

    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

    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.

  2. An Experimental Study to Evaluate the Effect of Memantine in Animal Models of Anxiety in Swiss Albino Mice

    PubMed Central

    AK, Afzal Khan; Shivaramegowda, Rekha M

    2015-01-01

    Background Due to the adverse effects produced by the present conventional medicines for anxiety disorders, research for newer drugs is still desirable. From the literature it is evident that NMDA receptors play a key role in animal models of anxiety. Aim The present study is done to evaluate the antianxiety effect of memantine in swiss albino mice. Materials and Methods The experimental study was conducted from November 2014 to January 2015. Animals were divided into four groups. Twelve mice were randomly allotted in each group. Animals in the first group received normal saline as a control 10ml/kg, lorazepam 0.5mg/kg was administered to second group, memantine 3mg/kg as a test drug was given to the third group and memantine 3mg/kg + lorazepam 0.5mg/kg was administered to the fourth group. All the drugs were given for 7 consecutive days by intraperitoneal route. Results Results were analyzed by one-way ANOVA followed by Post-hoc Tukey’s test. On the 1st day, memantine treated group did not show statistical significant anxiolytic effect in both the behavioural paradigms when compared to control group. On the 8th day, the animals showed significant decrease p<0.001 in step down latency period in shock free zone (185.4±3.87 Vs 278.3±5.49), significant increase p<0.001 in step down errors (6.8±0.78 Vs 1.4±0.19) and significant increase p<0.001 in total time spent in shock zone (32.1±2.22 Vs 5.6±0.6). In open field test, on 8th day the animals treated with memantine when compared to control group, showed significant increase p<0.001 in number of squares crossed (112.7± 2.69 Vs 83.2±2.96), time spent in central square (11.5±1.26 Vs 3.4±0.65), no. of rearings (32.4±2.61 Vs 17±1.81) and significant decrease p<0.001 in freezing time (15.2±1.12 Vs 20.2±2.29). Memantine showed synergistic antianxiety effect when combined with lorazepam. Conclusion Memantine showed significant anxiolytic effect in open field and passive avoidance response tests which are commonly used experimental models to assess anxiety states in animals. PMID:26435964

  3. Comparative pharmacokinetics and metabolism studies in lean and diet- induced obese mice: an animal efficacy model for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors.

    PubMed

    Wang, Mengmeng; Tian, Xianbin; Leung, Louis; Wang, Jianyao; Houvig, Nicole; Xiang, Jason; Wan, Zhao-Kui; Saiah, Eddine; Hahm, Seung; Suri, Vipin; Xu, Xin

    2011-01-01

    Diet-induced obese (DIO) mice have been commonly used as an animal model in the efficacy assessment for new drug candidates. Although high-fat feeding has been reported to cause profound physiological changes, including the expression of drug-metabolizing enzymes, limited studies have been reported regarding the effect of obesity/diabetes on pharmacokinetics (PK) in animals. In this study, we investigated PK profiles of three 11 -HSD-1 inhibitors in the DIO mice and compared them to the normal lean mice. After oral administration, the in vivo exposure (AUC) of all three compounds was higher in DIO mice, which was consistent with the observed lower systemic clearance (CL) in DIO mice compared to lean mice. As illustrated by Compound E, a compound metabolized predominantly by CYP3A and 2C, the metabolic profiles for Compound E were qualitatively similar between DIO and lean mice, but quantitatively lower in the DIO mice. Indeed, P-450 activities for CYP3A and 2C as well as 2D were found to be lower in liver microsomes prepared from DIO mice. The calculated hepatic clearance (CLH) from in vitro studies with liver microsomes correlated well with the observed in vivo clearance for both DIO and lean mice. The calculated oral bioavailability (F%) based on intrinsic hepatic clearance (C(LH, int)) predicted ~3 fold increase in F% for the DIO mice, which was comparable to the observed value. Collectively, these data suggest that the higher F% is most likely due to the lower first-pass effect in DIO mice. This study highlights the needs to take caution when extrapolating PK and exposure data from healthy animals to diseased animals in designing pharmacological studies. PMID:21198436

  4. Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

    PubMed Central

    Carryl, Heather; Swang, Melanie; Lawrence, Jerome; Curtis, Kimberly; Kamboj, Herman; Van Rompay, Koen K. A.; De Paris, Kristina; Burke, Mark W.

    2015-01-01

    Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems. PMID:26034832

  5. Suspended animation-like state protects mice from lethal hypoxia.

    PubMed

    Blackstone, Eric; Roth, Mark B

    2007-04-01

    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

  6. Mice examined in Animal Laboratory of Lunar Receiving Laboratory

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Landrum Young (seated), Brown and Root-Northrup, and Russell Stullken, Manned Spacecraft Center, examine mice in the Animal laboratory of the Lunar Receiving Laboratory which have been inoculated with lunar sample material. wish for peace for all mankind. astronauts will be released from quarantine on August 11, 1969. Donald K. Slayton (right), MSC Director of Flight Crew Operations; and Lloyd Reeder, training coordinator.

  7. Suppression of Locomotor Activity in Female C57Bl/6J Mice Treated with Interleukin-1β: Investigating a Method for the Study of Fatigue in Laboratory Animals

    PubMed Central

    Bonsall, David R.; Kim, Hyunji; Tocci, Catherine; Ndiaye, Awa; Petronzio, Abbey; McKay-Corkum, Grace; Molyneux, Penny C.; Scammell, Thomas E.; Harrington, Mary E.

    2015-01-01

    Fatigue is a disabling symptom in patients with multiple sclerosis and Parkinson’s Disease, and is also common in patients with traumatic brain injury, cancer, and inflammatory disorders. Little is known about the neurobiology of fatigue, in part due to the lack of an approach to induce fatigue in laboratory animals. Fatigue is a common response to systemic challenge by pathogens, a response in part mediated through action of the pro-inflammatory cytokine interleukin-1 beta (IL-1β). We investigated the behavioral responses of mice to IL-1β. Female C57Bl/6J mice of 3 ages were administered IL-1β at various doses i.p. Interleukin-1β reduced locomotor activity, and sensitivity increased with age. Further experiments were conducted with middle-aged females. Centrally administered IL-1β dose-dependently reduced locomotor activity. Using doses of IL-1β that caused suppression of locomotor activity, we measured minimal signs of sickness, such as hyperthermia, pain or anhedonia (as measured with abdominal temperature probes, pre-treatment with the analgesic buprenorphine and through sucrose preference, respectively), all of which are responses commonly reported with higher doses. We found that middle-aged orexin-/- mice showed equivalent effects of IL-1β on locomotor activity as seen in wild-type controls, suggesting that orexins are not necessary for IL-1β -induced reductions in wheel-running. Given that the availability and success of therapeutic treatments for fatigue is currently limited, we examined the effectiveness of two potential clinical treatments, modafinil and methylphenidate. We found that these treatments were variably successful in restoring locomotor activity after IL-1β administration. This provides one step toward development of a satisfactory animal model of the multidimensional experience of fatigue, a model that could allow us to determine possible pathways through which inflammation induces fatigue, and could lead to novel treatments for reversal of fatigue. PMID:26469939

  8. Companion animal adoption study.

    PubMed

    Neidhart, Laura; Boyd, Renee

    2002-01-01

    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

  9. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

    PubMed

    Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I

    2015-08-31

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894

  10. Animal studies of addictive behavior.

    PubMed

    Vanderschuren, Louk J M J; Ahmed, Serge H

    2013-04-01

    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

  11. DEVELOPMENTAL TOXICOGENOMIC STUDIES OF PFOA AND PFOS IN MICE.

    EPA Science Inventory

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

  12. Toxicological studies of wogonin in experimental animals.

    PubMed

    Qi, Qi; Peng, Jian; Liu, Wei; You, Qidong; Yang, Yong; Lu, Na; Wang, Guangji; Guo, Qinglong

    2009-03-01

    Wogonin, one active ingredient extract from the radix of Scutellaria baicalensis Georgi, is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties, especially the anticancer activity studied recently. However, no extensive safety studies have been conducted to date. In this paper, the acute and sub-chronic toxicity of the agent were determined using albino mice and Sprague-Dawley rats as animal models. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD(50) of wogonin administered by the intravenous injection was 286.15 mg/kg and the 95% confidence limit was 278.27-295.26 mg/kg. A long period of treatment with a high dose of wogonin (120 mg/kg) could induce heart injury in rats. These results provide a foundation for the further clinical investigation of this promising anticancer agent. PMID:19003942

  13. Animal studies on Spacelab-3

    NASA Technical Reports Server (NTRS)

    Schatte, C.; Grindeland, R.; Callahan, P.; Funk, G.; Lencki, W.; Berry, W.

    1986-01-01

    The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

  14. Animal studies on Spacelab-3

    NASA Technical Reports Server (NTRS)

    Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.

    1987-01-01

    The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

  15. Human SCARB2 Transgenic Mice as an Infectious Animal Model for Enterovirus 71

    PubMed Central

    Lin, Yi-Wen; Yu, Shu-Ling; Shao, Hsiao-Yun; Lin, Hsiang-Yin; Liu, Chia-Chyi; Hsiao, Kuang-Nan; Chitra, Ebenezer; Tsou, Yueh-Liang; Chang, Hsuen-Wen; Sia, Charles; Chong, Pele; Chow, Yen-Hung

    2013-01-01

    Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-α, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71. PMID:23451246

  16. Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice.

    PubMed

    Wei, Qingqing; Yin, Xiao-Ming; Wang, Mong-Heng; Dong, Zheng

    2006-01-01

    Tubular cell apoptosis is involved in ischemic renal failure, but the underlying mechanism is unclear. Bid, a proapoptotic Bcl-2 family protein, may regulate the intrinsic as well as the extrinsic pathway of apoptosis. In vivo, Bid is most abundantly expressed in the kidneys. However, the role played by Bid in renal pathophysiology is unknown. Our recent work demonstrated Bid activation during renal ischemia-reperfusion. The current study has determined the role of Bid in ischemic renal injury and renal failure using Bid-deficient mice. In wild-type C57BL/6 mice, Bid was proteolytically processed into active forms during renal ischemia-reperfusion, which subsequently targeted mitochondria. This was accompanied by the development of tissue damage and severe renal failure, showing serum creatinine of 3.0 mg/dl after 48 h of reperfusion. The same ischemic insult induced acute renal failure in Bid-deficient mice, which was nonetheless less severe than the wild-type, showing 1.3 mg/dl serum creatinine. In addition, Bid deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3 activation during 48 h of reperfusion. Compared with wild-type, animal death following renal ischemia was delayed in Bid-deficient mice. Collectively, the results suggest a role for Bid in ischemic renal injury and renal failure. PMID:16106037

  17. Animal imaging studies of potential brain damage

    NASA Astrophysics Data System (ADS)

    Gatley, S. J.; Vazquez, M. E.; Rice, O.

    To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Chubb, C.

    1987-10-01

    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.

  20. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    PubMed

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans. PMID:26067292

  1. NOD.H-2h4 mice: an important and underutilized animal model of autoimmune thyroiditis and Sjogren's syndrome.

    PubMed

    Braley-Mullen, Helen; Yu, Shiguang

    2015-01-01

    NOD.H-2h4 mice express the K haplotype on the NOD genetic background. They spontaneously develop thyroiditis and Sjogren's syndrome, but they do not develop diabetes. Although autoimmune thyroid diseases and Sjogren's syndrome are highly prevalent autoimmune diseases in humans, there has been relatively little emphasis on the use of animal models of these diseases for understanding basic mechanisms involved in development and therapy of chronic organ-specific autoimmune diseases. The goal of this review is to highlight some of the advantages of NOD.H-2h4 mice for studying basic mechanisms involved in development of autoimmunity. NOD.H-2h4 mice are one of relatively few animal models that develop organ-specific autoimmune diseases spontaneously, i.e., without a requirement for immunization with antigen and adjuvant, and in both sexes in a relatively short period of time. Thyroiditis and Sjogren's syndrome in NOD.H-2h4 mice are chronic autoimmune diseases that develop relatively early in life and persist for the life of the animal. Because the animals do not become clinically ill, the NOD.H-2h4 mouse provides an excellent model to test therapeutic protocols over a long period of time. The availability of several mutant mice on this background provides a means to address the impact of particular cells and molecules on the autoimmune diseases. Moreover, to our knowledge, this is the only animal model in which the presence or absence of a single cytokine, IFN-γ, is sufficient to completely inhibit one autoimmune thyroid disease, with a completely distinct autoimmune thyroid disease developing when it is absent. PMID:25727287

  2. Animal Study on Primary Dysmenorrhoea Treatment at Different Administration Times

    PubMed Central

    Pu, Bao-Chan; Fang, Ling; Gao, Li-Na; Liu, Rui; Li, Ai-zhu

    2015-01-01

    The new methods of different administration times for the treatment of primary dysmenorrhea are more widely used clinically; however, no obvious mechanism has been reported. Therefore, an animal model which is closer to clinical evaluation is indispensable. A novel animal experiment with different administration times, based on the mice oestrous cycle, for primary dysmenorrhoea treatment was explored in this study. Mice were randomly divided into two parts (one-cycle and three-cycle part) and each part includes five groups (12 mice per group), namely, Jingqian Zhitong Fang (JQF) 6-day group, JQF last 3-day group, Yuanhu Zhitong tablet group, model control group, and normal control group. According to the one-way ANOVAs, results (writhing reaction, and PGF2α, PGE2, NO, and calcium ions analysis by ELISA) of the JQF cycle group were in accordance with those of JQF last 3-day group. Similarly, results of three-cycle continuous administration were consistent with those of one-cycle treatment. In conclusion, the consistency of the experimental results illustrated that the novel animal model based on mice oestrous cycle with different administration times is more reasonable and feasible and can be used to explore in-depth mechanism of drugs for the treatment of primary dysmenorrhoea in future. PMID:25705236

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

    SciTech Connect

    Roszer, Tamas; Pintye, Eva; Benko', Ilona

    2008-12-08

    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.

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

    NASA Astrophysics Data System (ADS)

    Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

    2008-12-01

    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.

  5. Assessing the welfare of laboratory mice in their home environment using animal-based measures - a benchmarking tool.

    PubMed

    Spangenberg, Elin Mf; Keeling, Linda J

    2016-02-01

    Welfare problems in laboratory mice can be a consequence of an ongoing experiment, or a characteristic of a particular genetic line, but in some cases, such as breeding animals, they are most likely to be a result of the design and management of the home cage. Assessment of the home cage environment is commonly performed using resource-based measures, like access to nesting material. However, animal-based measures (related to the health status and behaviour of the animals) can be used to assess the current welfare of animals regardless of the inputs applied (i.e. the resources or management). The aim of this study was to design a protocol for assessing the welfare of laboratory mice using only animal-based measures. The protocol, to be used as a benchmarking tool, assesses mouse welfare in the home cage and does not contain parameters related to experimental situations. It is based on parameters corresponding to the 12 welfare criteria established by the Welfare Quality® project. Selection of animal-based measures was performed by scanning existing published, web-based and informal protocols, and by choosing parameters that matched these criteria, were feasible in practice and, if possible, were already validated indicators of mouse welfare. The parameters should identify possible animal welfare problems and enable assessment directly in an animal room during cage cleaning procedures, without the need for extra equipment. Thermal comfort behaviours and positive emotional states are areas where more research is needed to find valid, reliable and feasible animal-based measures. PMID:25801331

  6. A Comprehensive Study of Underground Animals Habitat

    NASA Astrophysics Data System (ADS)

    Klokov, A. V.; Zapasnoy, A. S.; Mironchev, A. S.; Yakubov, V. P.; Shipilova, S. S.

    2016-01-01

    This paper describes a method of studying the natural habitats of underground animals by the example of zokor. The purpose of the research is to find habitation of animals using unmanned aircraft and investigate networks of tunnels and burrows with ground penetrating radar "OKO-2". Geolocation data were processed by techniques developed by the authors.

  7. Epigenetic Case Studies in Agricultural Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In many biological processes, the regulation of gene expression involves epigenetic mechanisms. An altered pattern of epigenetic modification is central to many animal diseases. Using animal disease models, we have studied one of the major epigenetic components: DNA methylation. We characterized the...

  8. Clinical concepts derived from animal chemotherapy studies

    SciTech Connect

    Goldin, A.; Schabel, F.M.

    1981-01-01

    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.

  9. Satellite animal tracking feasibility studies

    NASA Technical Reports Server (NTRS)

    Buechner, H. K.

    1975-01-01

    A study was initiated in Tsavo National Park to determine movements and home ranges of individual elephants and their relations to overall distribution patterns and environmental factors such as rainfall. Methods used were radio tracking and observations of visually identifiable individuals. Aerial counts provided data on overall distribution. Two bulls and two cows were radio-tagged in Tsavo West and two bulls and four cows in Tsavo East, providing home range and movement data. The movements of individuals were useful in interpreting relatively major shifts in elephant distribution. Results point to the following preliminary conclusions: (1) elephants in the Tsavo area undertook long distance movements in fairly direct response to localized rainfall; (2) a subdivision of the overall population into locally distinct units may exist during the dry season but did not occur after significant rainfall; and (3) food appears to be the primary factor governing movements and distribution of elephants in the area.

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

    PubMed Central

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

    2014-01-01

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

  11. Bias During the Evaluation of Animal Studies?

    PubMed

    Knight, Andrew

    2012-01-01

    My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust. PMID:26486779

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

    PubMed

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

    2015-02-01

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

  13. An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

    PubMed

    Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

    2015-01-01

    Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. PMID:26111540

  14. Mice Drawer System: a Long Duration Animal Experiment on the International Space Station

    NASA Astrophysics Data System (ADS)

    Cotronei, Vittorio; Liu, Yi; Pignataro, Salvatore

    Mice represent one of the most important animal models for biomedical research. In the past decade mice have been used as surrogates to understand physiological adaption and its under-lying mechanisms to orbital spaceflight. A breakthrough in this field has been achieved with the launch of MDS experiment inside Shuttle Discovery (mission STS-128) on August 28, 2009 at 23:58 EST, and its re-entry to earth by Shuttle Atlantis (mission STS-129) on November 27 2009 at 9:47 EST, marking this as the first long duration animal experiment on the Interna-tional Space Station (ISS). This presentation will provide the life history and milestones starting from the project brainstorm to the post-ground activities of the recent MDS payload mission. The Italian Space Agency (ASI) initiated and coordinated this multi-disciplinary project by focusing on five areas: the development of a multi-purpose automated payload by industry; bio-compatibility tests of subsystems throughout various critical phases of the payload development by researchers, development of a ground segment to interface with NASA Payload Operations Center and three different geographically distributed Italian Operations Centers; establishment of an international tissue sharing program; specialized bio-specimen intercontinental shipment. With close collaboration with NASA, activities such as pre-flight payload acceptance, animal preparation, in-flight crew intervention and re-entry animal recovery were smoothly and swiftly accomplished.

  15. Animal Models in Studying Cerebral Arteriovenous Malformation

    PubMed Central

    Xu, Ming; Xu, Hongzhi; Qin, Zhiyong

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected. PMID:26649296

  16. Animal Models in Studying Cerebral Arteriovenous Malformation.

    PubMed

    Xu, Ming; Xu, Hongzhi; Qin, Zhiyong

    2015-01-01

    Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term "arteriovenous malformation," limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected. PMID:26649296

  17. Methods to Study Metastasis in Genetically Modified Mice.

    PubMed

    Kabeer, Farhia; Beverly, Levi J; Darrasse-Jèze, Guillaume; Podsypanina, Katrina

    2016-01-01

    Metastasis is often modeled by xenotransplantation of cell lines in immunodeficient mice. A wealth of information about tumor cell behavior in the new environment is obtained from these efforts. Yet by design, this approach is "tumor-centric," as it focuses on cell-autonomous determinants of human tumor dissemination in mouse tissues, in effect using the animal body as a sophisticated "Petri dish" providing nutrients and support for tumor growth. Transgenic or gene knockout mouse models of cancer allow the study of tumor spread as a systemic disease and offer a complimentary approach for studying the natural history of cancer. This introduction is aimed at describing the overall methodological approach to studying metastasis in genetically modified mice, with a particular focus on using animals with regulated expression of potent human oncogenes in the breast. PMID:26832689

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

    ERIC Educational Resources Information Center

    Christie, Michael A.; Hersch, Steven M.

    2004-01-01

    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…

  19. Hypoxia facilitates neurogenic dural plasma protein extravasation in mice: a novel animal model for migraine pathophysiology.

    PubMed

    Hunfeld, Anika; Segelcke, Daniel; Bäcker, Ingo; Mecheri, Badreddine; Hemmer, Kathrin; Dlugosch, Elisabeth; Andriske, Michael; Paris, Frank; Zhu, Xinran; Lübbert, Hermann

    2015-01-01

    Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT2B receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT2B receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice. Considering the role 5-HT2B receptors play in hypoxia-induced pulmonary vessel muscularization, we were encouraged to keep mice under hypoxic conditions and tested whether this treatment will render them susceptible to mCPP-induced dural PPE. Following four-week of hypoxia, PPE, associated with increased transendothelial transport, was induced by mCPP. The effect was blocked by sumatriptan. Chronic application of 5-HT2B receptor or nitric oxide synthase blockers during hypoxia prevented the development of susceptibility. Here we present a migraine model that distinguishes between a migraine-like state (hypoxic mice) and normal, normoxic mice and mimics processes that are related to chronic activation of 5-HT2B receptors under hypoxia. It seems striking, that chronic endogenous activation of 5-HT2B receptors is crucial for the sensitization since 5-HT2B receptor antagonists have strong, albeit delayed migraine prophylactic efficacy. PMID:26644235

  20. Hypoxia facilitates neurogenic dural plasma protein extravasation in mice: a novel animal model for migraine pathophysiology

    PubMed Central

    Hunfeld, Anika; Segelcke, Daniel; Bäcker, Ingo; Mecheri, Badreddine; Hemmer, Kathrin; Dlugosch, Elisabeth; Andriske, Michael; Paris, Frank; Zhu, Xinran; Lübbert, Hermann

    2015-01-01

    Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT2B receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT2B receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice. Considering the role 5-HT2B receptors play in hypoxia-induced pulmonary vessel muscularization, we were encouraged to keep mice under hypoxic conditions and tested whether this treatment will render them susceptible to mCPP-induced dural PPE. Following four-week of hypoxia, PPE, associated with increased transendothelial transport, was induced by mCPP. The effect was blocked by sumatriptan. Chronic application of 5-HT2B receptor or nitric oxide synthase blockers during hypoxia prevented the development of susceptibility. Here we present a migraine model that distinguishes between a migraine-like state (hypoxic mice) and normal, normoxic mice and mimics processes that are related to chronic activation of 5-HT2B receptors under hypoxia. It seems striking, that chronic endogenous activation of 5-HT2B receptors is crucial for the sensitization since 5-HT2B receptor antagonists have strong, albeit delayed migraine prophylactic efficacy. PMID:26644235

  1. A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

    SciTech Connect

    Granton, Patrick V.; Dubois, Ludwig; Elmpt, Wouter van; Hoof, Stefan J. van; Lieuwes, Natasja G.; De Ruysscher, Dirk

    2014-11-01

    Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23505511

  3. A Study of Statistical Errors in MICE

    NASA Astrophysics Data System (ADS)

    Forrest, D.; Soler, F. J. P.

    2010-03-01

    The Muon Ionization Cooling Experiment (MICE) will measure ionization cooling from a beam of muons at the Rutherford Appleton Laboratory in the UK. The aim of MICE is to measure a fractional drop in emittance, due to ionization cooling, of order 10% for a range of emittances and momenta, to an accuracy of 1%. A greater understanding of the statistical (as well as systematic) errors on emittance measurement in MICE is paramount to meeting this goal. This paper describes a study aimed at exploiting the computing power of the Grid to determine the number of muons necessary to meet the scientific goals of MICE. In this study, tens of thousands of G4MICE Monte Carlo simulations were run to determine the scaling laws that govern the fractional change in emittance as a function of the number of muons (N) in the simulation. By varying random conditions, the standard deviation of these distributions was studied as a function of N. The results of the study indicate that, due to the effect of correlations, of order 105 muons are required to meet the goal of MICE for large emittance beams, without which 106 would be required.

  4. Why do we study animal toxins?

    PubMed

    Zhang, Yun

    2015-07-18

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  5. Why do we study animal toxins?

    PubMed Central

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  6. Animal studies: summary, gaps, and future research.

    PubMed

    Pariza, M W

    1997-12-01

    Animal models are essential in cancer research but investigators should recognize the limits of the models they use. Because there is no ideal animal model, researchers should use the biological and biochemical diversity among the models to experimental advantage. The differences can tell us as much as the similarities. Fatty acid metabolism seems to play a role in hormone-dependent and hormone-independent cancers, and cell culture experiments have yielded much information on possible mechanisms. However, a knowledge gap exists between these studies and a full understanding of mechanisms in vivo. Mechanisms must be understood before the possible relevance of the findings to humans can be confidently assessed. There is little evidence to suggest that either trans fatty acids or oleic acid has any specific effect on carcinogenesis and it is unlikely that further study will reveal something important but heretofore overlooked. By contrast, there appear to be notable gaps in our understanding of n-3 fatty acids, linoleic acid, and conjugated linoleic acid in relation to possible effects on cancer in humans. The major knowledge gap, and our greatest challenge, is relating promising data from animal models and cell culture studies to the prevention of cancer in humans. PMID:9394712

  7. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  8. Toxicological, Pathological, and Teratological Studies in Animals with Cephradine

    PubMed Central

    Hassert, G. L.; DeBaecke, P. J.; Kulesza, J. S.; Traina, V. M.; Sinha, D. P.; Bernal, E.

    1973-01-01

    Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD50 in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD50 values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD50 in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/kg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed. PMID:4790617

  9. Developmental consequences of embryo and cell manipulation in mice and farm animals.

    PubMed

    McEvoy, T G; Robinson, J J; Sinclair, K D

    2001-10-01

    Advances in biotechnology in recent decades have revolutionized our understanding of early mammalian development and promise to provide ever more finely tuned and precisely targeted techniques for genetic enhancement of domestic animal species. In demonstrating what is both technically and biologically possible, not only in mice but also in larger animal species, research has provided hope that previously intractable diseases and genetic defects can be successfully combated. Crucial to this research is the ability to culture oocytes, embryos and somatic cells in vitro and to sustain their development without inducing adverse short- or long-term consequences. There is a need to refine current culture strategies in farm animal species to avoid jeopardizing their dependent technologies. A key to resolving current limitations of culture strategies is to identify, acknowledge and then address those features of in vitro culture that compromise early regulation of mammalian development. The aim of this review is to appraise critically in vitro embryo and somatic cell production strategies in the context of their impact on developmental competence and normality at embryonic, fetal and later stages. In addition, effects of physically manipulating embryos and cells, most notably via nuclear and gene transfer technologies, are considered with a view to identifying how detrimental consequences can be avoided. PMID:11570957

  10. Animal studies of charged particle-induced carcinogenesis.

    PubMed

    Bielefeldt-Ohmann, Helle; Genik, Paula C; Fallgren, Christina M; Ullrich, Robert L; Weil, Michael M

    2012-11-01

    The distribution of energy deposition in cells and tissues by high-charge, high-energy (HZE) nuclei differs considerably from that of low linear energy transfer (LET) radiation, raising concerns that charged particle exposure may be more efficient in inducing radiogenic cancers or may induce a different spectrum of tumors. The authors have performed a review of charged particle carcinogenesis in animals with the following observations. A limited number of animal studies with carcinogenesis endpoints have been performed to evaluate the effectiveness of HZE ions. These include the induction of skin and mammary tumors in the rat and Harderian gland tumors, acute myeloid leukemia (AML), and hepatocellular carcinomas in the mouse. In general, high relative biological effectiveness (RBE) has been reported for solid tumor induction. RBE dependence on HZE radiation quality has been most extensively characterized in studies of mouse Harderian gland tumorigenesis. In this model, the RBE increases with LET and plateaus in the 193-953 keV μm(-1) range. Unlike the results of solid tumor studies, a leukemogenesis study found 1 GeV nucleon(-1) 56Fe ions no more efficient than gamma-rays for AML induction. No novel tumor types have been observed in HZE irradiated animals as compared with those that occur spontaneously or following low-LET radiation exposures. Genetic background of the irradiated animals is critical; the tumor types induced in HZE irradiated mice depend on their strain background, and the incidence of HZE ion-induced mammary carcinogenesis in the rat is also strain dependent. PMID:23032886

  11. Immunology and Homeopathy. 3. Experimental Studies on Animal Models

    PubMed Central

    Bellavite, Paolo; Ortolani, Riccardo; Conforti, Anita

    2006-01-01

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

  12. Animal models for influenza virus transmission studies: a historical perspective.

    PubMed

    Bouvier, Nicole M

    2015-08-01

    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models-ferrets, mice, and guinea pigs-have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals. PMID:26126082

  13. Animal escapology II: escape trajectory case studies

    PubMed Central

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

    2011-01-01

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

  14. Krill Products: An Overview of Animal Studies

    PubMed Central

    Burri, Lena; Johnsen, Line

    2015-01-01

    Many animal studies have been performed with krill oil (KO) and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP) and krill protein concentrate (KPC) as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations. PMID:25961320

  15. Krill products: an overview of animal studies.

    PubMed

    Burri, Lena; Johnsen, Line

    2015-05-01

    Many animal studies have been performed with krill oil (KO) and this review aims to summarize their findings and give insight into the mechanism of action of KO. Animal models that have been used in studies with KO include obesity, depression, myocardial infarction, chronic low-grade and ulcerative inflammation and are described in detail. Moreover, studies with KO in the form of krill powder (KP) and krill protein concentrate (KPC) as a mix of lipids and proteins are mentioned and compared to the effects of KO. In addition, differences in tissue uptake of the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), when delivered in either phospholipid or triglyceride form, are addressed and the differential impact the delivery form has on gene expression profiles is explained. In our outlook, we try to highlight the potential of KO and KP supplementation in clinical settings and discuss health segments that have a high potential of showing krill product specific health benefits and warrant further clinical investigations. PMID:25961320

  16. Sjögren's syndrome: studying the disease in mice.

    PubMed

    Delaleu, Nicolas; Nguyen, Cuong Q; Peck, Ammon B; Jonsson, Roland

    2011-01-01

    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. PMID:21672284

  17. Study of Camelpox Virus Pathogenesis in Athymic Nude Mice

    PubMed Central

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

    2011-01-01

    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+CD8α+ 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

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

    SciTech Connect

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

    1987-11-01

    Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.

  19. Animal models for the study of the effects of spaceflight on the immune system

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, G.

    2003-10-01

    Animal models have been used to determine the effects of spaceflight on the immune system. Rats and rhesus monkeys have been the primary animals used for actual space flight studies, but mice have also been utilized for studies in ground-based models. The primary ground based model used has been hindlimb unloading of rodents, which is similar to the chronic bed-rest model for humans. A variety of immune responses have been shown to be modified when animals are hindlimb unloaded. These results parallel those observed when animals are flown in space. In general, immune responses are depressed in animals maintained in the hindlimb unloading model or flown in space. These results raise the possibility that spaceflight could result in decreased resistance to infection in animals.

  20. Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.

    PubMed

    Aiello, Rossana; Crupi, Rosalia; Leo, Antonio; Chimirri, Serafina; Rispoli, Vincenzo; Marra, Rosario; Citraro, Rita; Cuzzocrea, Salvatore; De Sarro, Giovambattista; Russo, Emilio

    2015-02-01

    One of the most peculiar characteristics of the stress response is the pronounced inter-individual and inter-strain variability both in behavioral and neurochemical outcomes. Several studies confirm that rodents belonging to the same or different strain and/or gender, when exposed to a stressor, may show behavioral and cognitive differences. We compared the effects of long-term betamethasone 21-phosphate disodium (BTM), a widely clinically used corticosteroid, on animal behavior and neurogenesis in CD1 and DBA/2 mice. BTM treatment, in CD1 mice, increased body weight gain and anxiety parameters while having pro-depressant effects. Furthermore, BTM significantly reduced neurogenesis in the dentate gyrus of the hippocampus. Finally, BTM treatment induced a significant impairment in memory and learning performance in the Morris water maze. At odds, BTM administration, in DBA/2 mice, caused a significant reduction in the body weight while not modifying anxiety parameters. In addition, both an increased synaptogenesis and neurogenesis were found. Similarly to CD1 mice, also in DBA/2 mice, memory and learning were impaired. Our data confirm that long-term exposure to corticosteroids can generate or aggravate psychiatric/neurologic disorders such as depression, anxiety, memory and learning. Our study did not reveal significant differences between corticosterone and BTM treatment in CD1 mice. In contrast, BTM treatment in mice with an anxious phenotype (DBA/2 mice) revealed some contrasting results indicating that genetic factors can influence corticosteroids dependent effects. Finally, our data further underline the need for a re-evaluation of neurogenesis role; the increased neurogenesis observed in DBA/2 mice and behavioral effects might be distinguished phenomena. PMID:25289489

  1. Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation

    NASA Astrophysics Data System (ADS)

    Reilhac, Anthonin; Boisson, Frédéric; Wimberley, Catriona; Parmar, Arvind; Zahra, David; Hamze, Hasar; Davis, Emma; Arthur, Andrew; Bouillot, Caroline; Charil, Arnaud; Grégoire, Marie-Claude

    2016-02-01

    In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies.

  2. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

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

    PubMed Central

    Steimer, Thierry

    2011-01-01

    Animal models can certainly be useful to find out more about the biological bases of anxiety disorders and develop new, more efficient pharmacological and/or behavioral treatments. However, many of the current “models of anxiety” in animals do not deal with pathology itself, but only with extreme forms of anxiety which are still in the normal, adaptive range. These models have certainly provided a lot of information on brain and behavioral mechanisms which could be involved in the etiology and physiopathology of anxiety disorders, but are usually not satisfactory when confronted directly with clinical syndromes. Further progress in this field will probably depend on the finding of endophenotypes which can be studied in both humans and animals with common methodological approaches. The emphasis should be on individual differences in vulnerability, which have to be included in animal models. Finally, progress will also depend on refining theoretical constructs from an interdisciplinary perspective, including psychiatry, psychology, behavioral sciences, genetics, and other neurosciences. PMID:22275854

  4. Lead hepatotoxicology: a study in an animal model.

    PubMed

    Sá, I; da Costa, M J P; Cunha, E M

    2012-03-01

    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

  5. The SCID mouse: relevance as an animal model system for studying human disease.

    PubMed Central

    Hendrickson, E. A.

    1993-01-01

    The simultaneous description some 5 years ago of two methods for the partial reconstitution of a human immune system in severe combined immune-deficient (SCID) mice (collectively, human:SCID mice) was met with great enthusiasm. At the time, it was hoped that human:SCID mice would provide experimental animal model systems for studying human disease and the human immune system. Many of these hopes have been borne out. Importantly, the experimental results obtained from these chimeric human/animal studies appear to be relevant to human disease and immune function. In spite of these glowing achievements, the SCID mouse may not represent the optimal experimental system with which to address these questions. The incomplete penetrance ("leakiness") of the scid mutation and the recent discovery that the mutation is not lymphoid specific, but rather affects a general DNA repair pathway, will only serve to complicate the interpretation of already complex biological interactions. Recently other immune-deficient mice have been described that appear to overcome one or both of these problems and thus these mice could represent improved hosts for the adaptive transfer of a human immune system. The current status of the SCID mouse in light of these new findings is discussed. PMID:8256843

  6. Implantation of bacteria from the digestive tract of man and various animals into gnotobiotic mice.

    PubMed

    Raibaud, P; Ducluzeau, R; Dubos, F; Hudault, S; Bewa, H; Muller, M C

    1980-11-01

    Fourteen microbial strains isolated from conventional rats were inoculated into axenic rats and mice receiving identical diets. The populations of these organisms which became established in the feces of gnotobiotic adult recipient rats and mice were quite similar. The only major difference was that one strain, belonging to the genus Clostridium, disappeared from the feces of gnotobiotic mice, whereas this strain became established in gnotobiotic rats. Most of the strictly anaerobic strains were absent or present only in small numbers before weaning in young rats and mice. A clear-cut barrier effect against Salmonella typhimurium was found in adult gnotobiotic mice colonized with a complex flora derived from a conventional chicken. The microflora established in these recipient mice exerted the same barrier effect when further transferred into axenic chickens. Inoculation of feces from a human donor into adult gnotobiotic recipient mice produced colonization by several strains from the donor, whereas other strains, belonging to the genera Bifidobacterium, Lactobacillus, and Clostridium were present in the donor, but did not persist in recipient mice. In these mice, nonetheless, the colonizing human fecal flora exerted an effective barrier against a toxigenic strain of Clostridium difficile. This barrier effect spontaneously disappeared several weeks later. Administration of clindamycin to the recipient mice led to large variations in the number of viable cells of C. difficile. PMID:7001883

  7. [The spleen in "nude" mice: an immunological and immunocytochemical study (author's transl)].

    PubMed

    Viac, J; Schmitt, D; Alario, A; Thivolet, J

    1976-01-01

    An immunological and immunocytochemical study to compare spleen cells of Nude (C57B1) and Swiss mice is reported. The percentage of surface immunoglobulins bearing lymphocytes is identical in both strains of animal (40%). An activated C3 receptor is present in the majority of these cells and has been demonstrated within the germinal centers in both cell suspensions and frozen tissue sections. The population of Fc receptor bearing cells is more heterogenous, but the percentage of these is nearly identical in both Swiss and Nude mice. T-cell specificity is identified with an anti-thymocyte and an antibrain antiserum using an indirect immunoperoxidase method. The percentage of cells detected with the anti-thymocyte antiserum is very low in the spleen of Nude mice (5%) compared to that in the Swiss mice (42%). In the Nude mice, the anti-brain antiserum detects up to 30% of the spleen cells which may be considered as precursors and, so far, these 30% of cells in the Nude mice are considered as "null" cells, compared to only 20% in normal mice. The localization of the various immunocompetent cells within the spleen tissue is determined by immunofluorescence, immunoenzymology and the EAC rosette test. This study leads to the conclusion that in the periarteriolar areas of the spleen of the Nude mice, immune cells are sparse but that thymo-independent cells are located in the same region in both species of mice. PMID:62550

  8. P388 leukemia in CDF₁ mice as the test system for studies of tumor-associated neoangiogenesis and hypercoagulation.

    PubMed

    Trashkov, A P; Panchenko, A V; Kayukova, E S; Korablev, R V; Pechatnikova, V A; Vasil'ev, A G; Anisimov, V N

    2015-02-01

    Blood levels of vascular endothelial growth factor, the main marker of angiogenesis activity, and coagulation hemostasis were studied in CDF1 mice with transplanted P-388 lymphocytic leukemia. Blood levels of vascular endothelial growth factor increased by 168% in mice with tumors. The animals developed the hypercoagulation syndrome manifesting in shorter activated partial thromboplastin time and prothrombin time and development of hyperfibrinogenemia. PMID:25708334

  9. Retrospective studies of unusual animal behavior as an earthquake predictor

    NASA Astrophysics Data System (ADS)

    Lott, Dale F.; Hart, Benjamin L.; Howell, Mary W.

    1981-12-01

    We systematically applied a retrospective interview approach to the study of unusual animal behavior prior to seven earthquakes in North, Central and South America. Data taken at some distance from two of the earthquakes provided a baseline rate of unusual animal behavior. In comparison to this baseline one earthquake was preceded by a significant increase in unusual animal behavior and four were not.

  10. Studying Biotechnological Methods Using Animations: The Teacher's Role

    ERIC Educational Resources Information Center

    Yarden, Hagit; Yarden, Anat

    2011-01-01

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

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

    SciTech Connect

    Price, Paul S. Keenan, Russell E.; Swartout, Jeffrey C.

    2008-11-15

    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.

  12. A study in animal ethics in New Brunswick.

    PubMed Central

    Schneider, B J

    2001-01-01

    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. PMID:11467182

  13. Pitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism.

    PubMed

    Kim, Kyoung-Shim; Kang, Young-Mi; Kang, Young; Park, Tae-Shin; Park, Hye-Yeon; Kim, Yoon-Jung; Han, Baek-Soo; Kim, Chun-Hyung; Lee, Chul-Ho; Ardayfio, Paul A; Han, Pyung-Lim; Jung, Bong-Hyun; Kim, Kwang-Soo

    2014-03-13

    Approximately 40-50% of all patients with Parkinson?s disease (PD) show symptoms and signs of depressive disorders, for which neither pathogenic understanding nor rational treatment are available. Using Pit3x-deficient mice, a model for selective nigrostriatal dopaminergic neurodegeneration, we tested depression-related behaviors and acute stress responses to better understand how a nigrostriatal dopaminergic deficit increases the prevalence of depressive disorders in PD patients. Pitx3-deficient mice showed decreased sucrose consumption and preference in the two-bottle free-choice test of anhedonia. Acute restraint stress increased c-Fos (known as a neuronal activity marker) expression levels in various brain regions, including the prefrontal cortex, striatum, nucleus accumbens, and paraventricular nucleus of the hypothalamus (PVN), in both Pitx3+/+ and -/- mice. However, the stress-induced increases in c-Fos levels in the cortex, dorsal striatum, and PVN were significantly greater in Pitx3-/- than +/+ mice, suggesting that signs of depressive disorders in parkinsonism are related to altered stress vulnerability. Based on these results, we propose that Pitx3-/- mice may serve as a useful genetic animal model for co-morbid depressive disorder and parkinsonism. PMID:24480473

  14. Safety study of Ciprofloxacin in newborn mice.

    PubMed

    Bourgeois, Thomas; Delezoide, Anne-Lise; Zhao, Wei; Guimiot, Fabien; Adle-Biassette, Homa; Durand, Estelle; Ringot, Maud; Gallego, Jorge; Storme, Thomas; Le Guellec, Chantal; Kassaï, Behrouz; Turner, Mark A; Jacqz-Aigrain, Evelyne; Matrot, Boris

    2016-02-01

    Ciprofloxacin, a broad-spectrum antimicrobial agent belonging to the fluoroquinolone family, is prescribed off-label in infants less than one year of age. Ciprofloxacin is included in the European Medicines Agency priority list of off-patent medicinal products requiring evaluation in neonates. This evaluation is undergoing within the TINN (Treat Infections in Neonates) FP7 EU project. As part of the TINN project, the present preclinical study was designed to assess the potential adverse effects of Ciprofloxacin on neurodevelopment, liver and joints in mice. Newborn mice received subcutaneous Ciprofloxacin at 10, 30 and 100 mg/kg/day from 2 to 12 postnatal days. Peak plasma levels of Ciprofloxacin were in the range of levels measured in human neonates. We examined vital functions in vivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30 mg/kg/day. In contrast, administration at 100 mg/kg/day delayed weight gain, impaired cardiorespiratory and psychomotor development, caused inflammatory infiltrates in the connective tissues surrounding the knee joint, and moderately increased extramedullary hematopoiesis. The present study pleads for careful watching of cardiorespiratory and motor development in neonates treated with Ciprofloxacin, in addition to the standard surveillance of arthrotoxicity. PMID:26627140

  15. SYRCLE’s risk of bias tool for animal studies

    PubMed Central

    2014-01-01

    Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies. PMID:24667063

  16. Urea Transporter Physiology Studied in Knockout Mice

    PubMed Central

    Li, Xuechen; Chen, Guangping; Yang, Baoxue

    2012-01-01

    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. PMID:22745630

  17. Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

    PubMed

    Gur'yanova, N N; Bugaeva, L I; Lebedeva, S A; Tekutova, T V; Dugina, Yu L; Petrov, V I; Epshtein, O I

    2014-05-01

    We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine. PMID:24915946

  18. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    PubMed Central

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

    2014-01-01

    Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease. PMID:24553602

  19. Animal models for the study of leishmaniasis immunology.

    PubMed

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

    2014-01-01

    Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers ("low" 1 × 10(2) and "high" 1 × 10(6)) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease. PMID:24553602

  20. Peripheral white blood cells profile of biodegradable metal implant in mice animal model

    NASA Astrophysics Data System (ADS)

    Paramitha, Devi; Noviana, Deni; Estuningsih, Sri; Ulum, Mokhamad Fakhrul; Nasution, Ahmad Kafrawi; Hermawan, Hendra

    2015-09-01

    Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

  1. Peripheral white blood cells profile of biodegradable metal implant in mice animal model

    SciTech Connect

    Paramitha, Devi; Noviana, Deni Estuningsih, Sri; Ulum, Mokhamad Fakhrul; Nasution, Ahmad Kafrawi; Hermawan, Hendra

    2015-09-30

    Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

  2. Biological studies on the effect of estrogen on experimentally induced asthma in mice.

    PubMed

    El-Desouki, Nabila I; Tabl, Ghada A; Elkhodary, Yasmin A A

    2016-01-01

    This study evaluates the influence of estrogen hormone on the experimentally induced asthma in male mice. The animals were divided into four groups, with 20 mice in each group; group I (control mice) included mice that received no treatment, group II included mice that received intraperitoneal estrogen injection (0.25 mg/kg body weight (bw), twice on day 28 of the experiment), group III (asthmatic mice) included asthmatic mice that received intraperitoneal injection of two doses of ovalbumin (OVA; 2 µg of OVA mixed with 100 µg of aluminum potassium sulfate) on days 1 and 14 of the experiment and then challenged intranasally with a single dose of OVA (50 µg dissolved in 0.05 ml phosphate-buffered saline; PBS) on day 28 of the experiment, and group IV (asthmatic mice treated with estrogen) included asthma model male mice that received the estrogen (0.5 mg/kg bw in 40 ml PBS, twice on the day 28 of the experiment). The immunohistochemical studies observed a marked intensity of CD15 immunoreactivity in the lung tissues of asthma model mice. Physiological results recorded that the total and differential count of leukocytes in bronchoalveolar lavage fluid (BALF) of asthma model mice recorded a significant increase in the number of leukocytes especially in the number of eosinophil cells. The BALF of asthma model mice showed high levels of interleukins 4 and 5 (IL-4 and IL-5), and there was a significant decrease in both the levels of IL-4 and IL-5 in BALF of asthma model mice treated with estrogen. In conclusion, the obtained results indicated that the asthma is responsible for certain immunohistochemical and physiological alterations induced in lung tissues of mice. The administration of estrogen to asthmatic male mice could improve these changes. For this reason, the present findings support the possible role of estrogen in modulating the inflammatory effects caused by asthma in male mice and may be helpful to cure many asthmatic progressions. PMID:23863957

  3. The cerebellum: Comparative and animal studies.

    PubMed

    Sultan, Fahad; Glickstein, Mitchel

    2007-01-01

    The cerebellum has a uniform cellular structure and microcircuitry, but the size of its subdivisions varies greatly among vertebrates. This variability is a challenge to anatomists to attempt to relate size differences to differences in characteristic behaviour. Here we review the early work of Lodewijk Bolk on the mammalian cerebellum and relate his observations to unfolded maps of the rodent cerebella. We further take insights from the comparative anatomy of the bird cerebella and find that cerebellar enlargement in large brains is not a passive consequence of overall brain enlargement, but is related to specific behaviour. We speculate that for some rodents (e.g., squirrels), primates and some large-brained birds (crows, parrots and woodpeckers), specifically enlarged cerebella are associated with either the elaboration of forelimb control (squirrels and primates) or in the case of the birds with beak control. The elaboration of such motor behaviour combined with increased visual control could have helped to furnish manipulative skills in these animals. Finally, we review the connections of the mammalian cerebellum and show that several pieces of experimental evidence point to an important function of the cerebellum in sensory control of movement reflex adjustment, and motor learning. PMID:17786812

  4. Animal Models to Study Gluten Sensitivity1

    PubMed Central

    Marietta, Eric V.; Murray, Joseph A.

    2012-01-01

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

  5. An animal-specific FSI model of the abdominal aorta in anesthetized mice.

    PubMed

    Trachet, Bram; Bols, Joris; Degroote, Joris; Verhegghe, Benedict; Stergiopulos, Nikolaos; Vierendeels, Jan; Segers, Patrick

    2015-06-01

    Recent research has revealed that angiotensin II-induced abdominal aortic aneurysm in mice can be related to medial ruptures occurring in the vicinity of abdominal side branches. Nevertheless a thorough understanding of the biomechanics near abdominal side branches in mice is lacking. In the current work we present a mouse-specific fluid-structure interaction (FSI) model of the abdominal aorta in ApoE(-/-) mice that incorporates in vivo stresses. The aortic geometry was based on contrast-enhanced in vivo micro-CT images, while aortic flow boundary conditions and material model parameters were based on in vivo high-frequency ultrasound. Flow waveforms predicted by FSI simulations corresponded better to in vivo measurements than those from CFD simulations. Peak-systolic principal stresses at the inner and outer aortic wall were locally increased caudal to the celiac and left lateral to the celiac and mesenteric arteries. Interestingly, these were also the locations at which a tear in the tunica media had been observed in previous work on angiotensin II-infused mice. Our preliminary results therefore suggest that local biomechanics play an important role in the pathophysiology of branch-related ruptures in angiotensin-II infused mice. More elaborate follow-up research is needed to demonstrate the role of biomechanics and mechanobiology in a longitudinal setting. PMID:25824368

  6. The CYP2D6 animal model: how to induce autoimmune hepatitis in mice.

    PubMed

    Hintermann, Edith; Ehser, Janine; Christen, Urs

    2012-01-01

    Autoimmune hepatitis is a rare but life threatening autoimmune disease of the liver of unknown etiology(1,2). In the past many attempts have been made to generate an animal model that reflects the characteristics of the human disease (3-5). However, in various models the induction of disease was rather complex and often hepatitis was only transient(3-5). Therefore, we have developed a straightforward mouse model that uses the major human autoantigen in type 2 autoimmune hepatitis (AIH-2), namely hCYP2D6, as a trigger(6). Type 1 liver-kidney microsomal antibodies (LKM-1) antibodies recognizing hCYP2D6 are the hallmark of AIH-2(7,8). Delivery of hCYP2D6 into wildtype FVB or C57BL/6 mice was by an Adenovirus construct (Ad-2D6) that ensures a direct delivery of the triggering antigen to the liver. Thus, the ensuing local inflammation generates a fertile field(9) for the subsequent development of autoimmunity. A combination of intravenous and intraperitoneal injection of Ad-2D6 is the most effective route to induce a long-lasting autoimmune damage to the liver (section 1). Here we provide a detailed protocol on how autoimmune liver disease is induced in the CYP2D6 model and how the different aspects of liver damage can be assessed. First, the serum levels of markers indicating hepatocyte destruction, such as aminotransferases, as well as the titers of hCYP2D6 antibodies are determined by sampling blood retroorbitaly (section 2). Second, the hCYP2D6-specific T cell response is characterized by collecting lymphocytes from the spleen and the liver. In order to obtain pure liver lymphocytes, the livers are perfused by PBS via the portal vein (section 3), digested in collagen and purified over a Percoll gradient (section 4). The frequency of hCYP2D6-specific T cells is analyzed by stimulation with hCYP2D6 peptides and identification of IFNγ-producing cells by flow cytometry (section 5). Third, cellular infiltration and fibrosis is determined by immunohistochemistry of liver sections (section 6). Such analysis regimen has to be conducted at several times after initiation of the disease in order to prove the chronic nature of the model. The magnitude of the immune response characterized by the frequency and activity of hCYP2D6-specific T and/or B cells and the degree of the liver damage and fibrosis have to be assessed for a subsequent evaluation of possible treatments to prevent, delay or abrogate the autodestructive process of the liver. PMID:22331063

  7. Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

    PubMed Central

    Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

    2000-01-01

    The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

  8. Progress of genome wide association study in domestic animals

    PubMed Central

    2012-01-01

    Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described. PMID:22958308

  9. Preflight studies on tolerance of pocket mice to oxygen and heat. III - Effects on eyes

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Corbett, R. L.; Black, S.; Takahashi, A.; Leaffer, D.

    1975-01-01

    A study was made of the eyes of eight pocket mice exposed to oxygen at partial pressures of 8, 10, or 12 psi over a period of 7 d. At the termination of the exposure, the animals were decompressed to sea-level O2, either immediately or over a period of 30, 60, or 90 min. No pathological changes were found in any of the eyes, except in the retina of one of the animals exposed to 12 psi O2. Here, only a single rod photoreceptor was found damaged, an observation not regarded as significant. Hence, an oxygen partial pressure as high as 12 psi in the canister in which pocket mice were expected to fly on Apollo XVII would probably have no deleterious effect on the eyes of the animals.

  10. Animal models for the study of hepatitis C virus infection and related liver disease.

    PubMed

    Bukh, Jens

    2012-05-01

    Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T- and B- cell deficient mice with human chimeric livers. Although these mice cannot be used in studies of adaptive immunity, they have provided new insights into HCV neutralization, interactions between virus and receptors, innate host responses, and therapeutic approaches. Recent progress in developing genetically humanized mice is exciting, but these models only permit studies of specific steps in the HCV life cycle and have limited or no viral replication. PMID:22537434

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

    PubMed

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

    2014-11-15

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

  12. Animal models of chronic tympanic membrane perforation: in response to plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice.

    PubMed

    Wang, Allen Y; Shen, Yi; Wang, Jeffrey T; Eikelboom, Robert H; Dilley, Rodney J

    2014-01-01

    Tympanic membrane perforations (TMP) are relatively common but are typically not treated in their acute stage, as most will heal spontaneously in 7-10 days. Those cases which fail to heal within 3 months are called chronic TMP which attract surgical intervention (e.g. myringoplasty), typically with a temporalis fascia autograft. New materials for the repair of chronic TMP are being developed to address deficiencies in the performance of autografts by undergoing evaluation in animal models prior to clinical study. However, there is currently a lack of ideal chronic TMP animal models available, hindering the development of new treatments. Various techniques and animal species have been investigated for the creation of chronic TMP with varied success. In the present commentary, we bring to the attention of readers the recent report by Shen et al. in Journal of Translational Medicine. The study reported the creation of a chronic TMP animal model in plasminogen gene deficient mice. However, the short observation time (9, 19 days), lack of success rate and the scarcity of solid evidence (e.g. otoscopic & histologic images) to confirm the chronicity of TMP warrant a more thorough discussion. PMID:24669846

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

    PubMed

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

    2008-12-01

    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

  14. Treatment for Traumatic Brain Injury in Mice Using Transcranial Magnetic Stimulation: A Preliminary Study

    NASA Astrophysics Data System (ADS)

    Carr, Alexandria; Zenitsky, Gary; Crowther, Lawrence; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) is a non-invasive surgery-free tool used to stimulate the brain by time-varying magnetic fields. TMS is currently being investigated as a treatment for neurological disorders such as depression, Parkinson's disease and TBI. Before moving to human TMS/TBI trials, animal testing should be pursued to determine suitability and adverse effects. As an initial study, four healthy mice were treated with TMS at different power levels to determine short-term behavioral effects and set a control group baseline. The mouse's behavior was studied using the Rotorod test, which measures the animal's latency to fall off a rotating rod, and the Versamax test, which measures horizontal and vertical movement, and total distance traveled. The Rotorod test has shown for TMS power levels >=90% the mice begin to fall directly post-treatment. Similarly, the Versamax test has shown for power levels >=80% the mice are less mobile directly post-treatment. Versamax mobility was found to return to normal the day following treatment. These mice were housed in the facility for 4 months and the behavioral tests were repeated. Versamax results showed there was no significant variation in mobility indicating there are no long-term side effects of TMS treatment on the mice. This work was supported by the Barbara and James Palmer Endowment and the Carver Charitable Trust at the Department of Electrical and Computer Engineering, Iowa State University.

  15. Antipsychotic induced metabolic abnormalities: an interaction study with various PPAR modulators in mice.

    PubMed

    Arulmozhi, D K; Dwyer, D S; Bodhankar, S L

    2006-10-01

    Abnormalities in glucose and lipid regulation have been reported in schizophrenia during antipsychotic medications. The objectives of the present study were to evaluate the effect of various peroxisome proliferator-activated receptor modulators viz. glimepiride, rosiglitazone and fenofibrate on chlorpromazine, clozapine and ziprasidone induced hyperglycemia and hyperlipidemia in mice. Male Swiss albino mice were orally treated with chlorpromazine, clozapine and ziprasidone concurrently with the antidiabetic medications for 7 days. Plasma glucose, insulin and triglyceride levels were determined at the end of the study. Chlorpromazine and clozapine elevated the glucose and triglyceride levels in normal mice, with no effect on insulin but ziprasidone increased the basal triglyceride and insulin levels and did not have any effect on glucose. Glimepiride and rosiglitazone showed beneficial glucose and triglyceride lowering effects in chlorpromazine and clozapine animals and no effect on insulin levels. Fenofibrate significantly reduced the glucose levels only in animals treated with clozapine, and exhibited significant reduction of triglyceride levels in chlorpromazine, clozapine and ziprasidone treated animals. All three antidiabetic/hypolipidemic agents lowered triglyceride and insulin levels in ziprasidone treated animals. The results of the present studies suggest that hyperglycemia, hyperinsulinemia and hypertriglyceridemia induced by various antipsychotics may involve diverse mechanisms. PMID:16828808

  16. Cytogenetic studies of mice chronically fed carcinogens

    SciTech Connect

    Director, A.E.; Ramsey, M.J.; Tucker, J.D.

    1997-10-01

    Over the past few years, we have carried out chronic feeding studies in C57BL/6 female mice. These experiments examined the effect of the chronic ingestion of a single chemical carcinogen on chromosomes. The carcinogens studied were PhIP,MeIQx, cyclophosphamide and urethane. These studies used traditional assays, such as SCEs and MN, as well as chromosome painting. In all four cases, the traditional assays showed an increase in the frequency of lesions, demonstrating that the chemicals, and/or their reactive metabolites, reached the target nuclei. This, however, seemed at odds with the data obtained from chromosome painting, which did not show an increase in the frequency of stable chromosome aberrations. This discrepancy between traditional assays and chromosome painting may be due to the nature of the lesions that each assay identifies. The traditional assays tend to identify lesions on the chromatid level, where as chromosome painting identifies lesions on the chromosome level requires two or more DNA double strand breaks occurring proximally in both time and space. In other words, for exposure to a chemical carcinogen to induce an increase in chromosome aberrations as measured by chromosome painting, the chemical, or its metabolites, would have to cause a large number of double strand breaks. By applying this logic to the data obtained from the four chronic feeding studies, one can infer that the chronic ingestion of chemical carcinogens does not result in the frequent formation of double strand breaks and therefore, does not result in the frequent formation of double strand breaks and therefore, does not result in increased frequencies of stable chromosome aberrations. We must, therefore, look elsewhere for the mechanism(s) underlying carcinogenesis due to chronic exposure to chemical carcinogens.

  17. NASA Animal Enclosure Module Mouse Odor Containment Study for STS-107 September 15, 1999;SJSU Odor Panel Data

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Mele, Gary D.; Poffenroth, Mary; Young, Cliff

    2000-01-01

    Experiment #153 by Scott Brady is manifested for shuttle flight STS-107. This evaluation of space flight induced stress and its effects on neuronal plasticity will use 18 six month old C57Bl/6 male mice. A 21 day evaluation study was proposed to determine the length of time groups of 6, 9, or 12 mice could be housed in the Animal Enclosure Module (AEM) without odor breakthrough. This study was performed at NASA-Ames Research Center beginning on September 15, 1999. NASA personnel, were responsible for animal care, maintenance, facilities, hardware, etc. San Jose State personnel performed the odor panel evaluations and data reduction. We used similar procedures and methods for earlier tests evaluating female mice.

  18. The FVB/N mice: A well suited strain to study learning and memory processes using olfactory cues.

    PubMed

    Girard, Stéphane D; Escoffier, Guy; Khrestchatisky, Michel; Roman, François S

    2016-01-01

    The FVB/N mice are well suited to generate transgenic animals. These mice are also particularly sensitive to seizures and neurodegeneration induced by systemic administration of chemoconvulsants and are very useful to model epilepsy. However, previous studies report strong cognitive and visual impairments suggesting this background unsuitable for behavioral analysis. In this study, we assessed and compared learning abilities of FVB/N mice to the well characterized C57BL/6 strain using the olfactory tubing maze, a non-visual hippocampus-dependent task in which the mice were trained to learn odor-reward associations. Exploratory behavior and spontaneous locomotor activity were then compared using the open field test. We demonstrated that FVB/N mice were able to learn the task, reaching at the end of the test a high percentage of correct responses. Interestingly, the performance of the FVB/N mice was at least similar to that of the C57BL/6 mice. Moreover, in contrast to previous reports, the FVB/N mice displayed a spontaneous locomotor activity lower than C57BL/6 mice. Our study demonstrated that FVB/N mice are not cognitively impaired and that their learning and memory performance can be assessed when the task is based on olfaction rather than vision. PMID:26365456

  19. Relevance of experimental animal studies to the human experience

    SciTech Connect

    Fry, R.J.M.

    1982-01-01

    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.

  20. Childhood cruelty to animals: a tri-national study.

    PubMed

    Mellor, David; Yeow, James; Mohd Hapidzal, Noor Fizlee; Yamamoto, Takashi; Yokoyama, Akimitsu; Nobuzane, Yosuke

    2009-12-01

    Childhood cruelty to animals is a symptom of conduct disorder that has been linked to the perpetration of violence in later life. Research has identified several factors associated with its etiology, including social factors. However, no cross-cultural studies on this phenomenon have been reported. This study investigated childhood cruelty to animals in Japan, Australia and Malaysia. Parents of 1,358 children between the ages of 5 and 13 years completed the Children's Attitudes and Behaviours towards Animals questionnaire (CABTA) which assesses Typical and Malicious Cruelty to animals. Analyses revealed no overall differences between children from these countries on either scale. However, younger boys were more likely to be cruel than younger girls in each country, and younger children in Australia and Japan were more likely to be cruel that older children in those countries. The findings are discussed in relation to previous research, and recommendations for future studies are suggested. PMID:19449100

  1. Diet and cancer prevention studies in p53-deficient mice.

    PubMed

    Hursting, S D; Perkins, S N; Phang, J M; Barrett, J C

    2001-11-01

    Progress in mechanism-based cancer prevention research may be facilitated by the use of animal models displaying specific genetic susceptibilities for cancer such as mice deficient in the p53 tumor suppressor gene, the most frequently altered gene in human cancer. We observed in p53-knockout (p53-/-) mice that calorie restriction (CR; 60% of the control group's intake of carbohydrate energy) increased the latency of spontaneous tumor development (mostly lymphomas) approximately 75%, decreased serum insulin-like growth factor (IGF)-1 and leptin levels, significantly slowed thymocyte cell cycle traverse and induced apoptosis in immature thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and 1 d/wk of food deprivation each significantly delayed spontaneous tumor development (a mix of lymphomas, sarcomas and epithelial tumors) and decreased serum IGF-1 and leptin levels even when begun late in life. We have also developed a rapid and relevant p53+/- mouse mammary tumor model by crossing p53-deficient mice with MMTV-Wnt-1 transgenic mice, and found that CR and 1 d/wk food deprivation significantly increased mammary tumor latency (greater than twofold) and reduced the mean serum IGF-1 and leptin levels to <50% of that of control mice (P < 0.0001). In addition, fluasterone, fenretinide and soy each delayed tumor development but had little effect on IGF-1 or leptin levels. We have capitalized on the susceptibility of p53+/- mice to chronic, low dose, aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches such as cyclooxygenase-2 inhibition. As demonstrated by these examples, mice with specific (and human-like) genetic susceptibilities for cancer provide powerful new tools for testing and characterizing interventions that may inhibit the process of carcinogenesis in humans. PMID:11694654

  2. Pharmacological and haematological study of shol fish (Channa striatus) skin extract on experimental animal.

    PubMed

    Karmakar, Surajit; Dasgupta, S C; Gomes, A

    2002-01-01

    Snake head fish Channa striatus (locally called 'shol') skin extract (SFSE) was examined for certain pharmacological and haematological effects on experimental animals. LD50 of SFSE was found to be 6 mg/20gm (iv) in male albino mice. SFSE potentiated pentobarbitone induced sleeping time in male albino mice and produced hypothermia. Low dose of SFSE decreased respiratory rate in rat and guineapig and high dose produced apnoea leading to death. On isolated toad and guineapig heart, SFSE significantly decreased rate and amplitude of contraction leading to temporary blockade, which returned after repeated wash. On isolated nerve muscle preparations, SFSE produced irreversible blockade of twitch response. SFSE induced quick contraction on isolated guineapig ileum, which was antagonised by atropine and cyproheptadine. SFSE did not possess haemolytic and haemorrhagic activity but produced anaemia in male albino mice. A neurotoxic compound (fluoroscent and ninhydrin positive) was isolated from SFSE by thin layer chromatography. This compound (CS-NT) was lethal in male albino mice, produced death by apnoea in rat and produced irreversible blockade of isolated nerve-muscle preparation. This study confirms that the skin of Channa striatus possesses toxic, and lethal components, which needs further detailed study. PMID:12561982

  3. Controlling airborne cues to study small animal navigation

    PubMed Central

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

    2012-01-01

    Small animals like nematodes and insects analyze airborne chemical cues to infer the direction of favorable and noxious locations. In these animals, the study of navigational behavior evoked by airborne cues has been limited by the difficulty of precise stimulus control. We present a system that enables us to deliver gaseous stimuli in defined spatial and temporal patterns to freely moving small animals. We use this apparatus, in combination with machine vision algorithms, to assess and quantify navigational decision-making of Drosophila larvae in response to ethyl acetate (a volatile attractant) and carbon dioxide (a gaseous repellant). PMID:22245808

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

    PubMed

    Williams, Colin J; Weinberg, Martin S

    2003-12-01

    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

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

    PubMed

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

    2014-01-01

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

  6. Preliminary study on the production of transgenic mice harboring hepatitis B virus X gene

    PubMed Central

    Zhu, Huan-Zhang; Cheng, Guo-Xiang; Chen, Jian-Qu; Kuang, Shu-Yuan; Cheng, Yong; Zhang, Xin-Li; Li, Hou-Da; Xu, Shao-Fu; Shi, Jing-Quan; Qian, Geng-Sun; Gu, Jian-Ren

    1998-01-01

    AIM: To establish transgenic mice lineage harboring hepatitis B virus X gene and to provide an efficient animal model for studying the exact role of the HBx gene in the process of hepatocarcinogenesis. METHODS: The HBx transgenic mice were produced by microinjecting the construct with X gene of HBV (subtype adr) DNA fragment into fertilzed eggs derived from inbred C57BL/6 strain; transgenic mice were identified by using Nested PCR; expression and phenotype of HBx gene were analyzed in liver from transgenic mic at the age of 8 weeks by RT-PCR, pathologic examination and periodic acid-schiff staining (PAS), respectively. RESULTS: Five hundred and fourteen fertilized eggs of C57 BL/6 mice were microinjected with recombinant retroviral DNA fragment, and 368 survival eggs injected were transferred to the oviducts of 18 pseudopregnant recipient mice, 8 of them became pregnant and gave birth to 20 F1 offspring. Of 20 offsprings, four males and two females carried the hybrid gene (HBx gene). Four male mice were determined as founder, named X1, X5, X9 and X15. These founders were back crossed to set up F1 generations with other ibred C57BL/6 mice or transgenic littermates, respectively. Transmission of HBx gene in F1 offspring of X1, X5 and X9 except in X15 followed Mendelian rules. The expression of HBx mRNA was detected in liver of F1 offspring from the founder mice (X1 and X9), which showed vacuolation lesion and glycogen positive foci. CONCLUSION: Transgenic mice harboring HBx gene were preliminarily established. PMID:11819365

  7. Smoking during pregnancy: lessons learned from epidemiological studies and experimental studies using animal models.

    PubMed

    Abbott, Louise C; Winzer-Serhan, Ursula H

    2012-04-01

    Numerous epidemiological studies in the human population clearly indicate that smoking while pregnant has deleterious effects on fetal development as well as long-term adverse consequences on postnatal development and maturation of several organ systems. Low birth weight, sudden infant death syndrome (SIDS), behavioral disorders including attention deficit hyperactivity disorder (ADHD), externalizing and internalizing behavioral problems and conduct disorders in children have all been linked to prenatal exposure to tobacco smoke. The major pharmacologically active chemical found in tobacco smoke is nicotine, and prenatal exposure to nicotine has been shown to have significant effect on the development of multiple organ systems, including the nervous, respiratory, and cardiovascular systems. In this review, we define mainstream and sidestream smoke, summarize the major classes of compounds found in cigarette smoke, and describe how use of laboratory animal models can be used to assess mechanisms of toxicity and risk in the human population in general. We then discuss the association with smoking during pregnancy and the occurrence of reduced lung function, low birth weight, the incidence of congenital structural malformations, SIDS, ADHD, cognitive impairment, and mood disorders in children, and review pertinent experimental studies using a variety of animal models of developmental nicotine exposure, including, rats, mice, monkeys, lambs, and pigs that have increased our understanding of the pathophysiology of these disorders. PMID:22394313

  8. High-field small animal magnetic resonance oncology studies

    NASA Astrophysics Data System (ADS)

    Bokacheva, Louisa; Ackerstaff, Ellen; LeKaye, H. Carl; Zakian, Kristen; Koutcher, Jason A.

    2014-01-01

    This review focuses on the applications of high magnetic field magnetic resonance imaging (MRI) and spectroscopy (MRS) to cancer studies in small animals. High-field MRI can provide information about tumor physiology, the microenvironment, metabolism, vascularity and cellularity. Such studies are invaluable for understanding tumor growth and proliferation, response to treatment and drug development. The MR techniques reviewed here include 1H, 31P, chemical exchange saturation transfer imaging and hyperpolarized 13C MRS as well as diffusion-weighted, blood oxygen level dependent contrast imaging and dynamic contrast-enhanced MRI. These methods have been proven effective in animal studies and are highly relevant to human clinical studies.

  9. Study on parasites from farm animals in Kuwait.

    PubMed

    Majeed, Qais A H; Alazemi, Maha S; Henedi, Adawia A M; Tahrani, Laila M A

    2015-04-01

    No doubt, farm animals are essential as a source of milk, protein, and leather and wool ... etc. But, they are always exposed to ecto- and endo-parasites, which cause diseases conditions that may end in death. This study evaluated farm animal parasitosis. Thus, different animal farms were visited to collect fecal samples and data to determine the infection rates with parasites and the relationship between animal management and parasitism in Kuwait. Out of 86, 17, 20, 96 & 52 cattle, sheep, goats, horses and camels examined, 5.5, 17.5, 10, 9.3 and 2.5% respectively were infected with different parasites. These parasites were Ascarids in cattle and horses, Strongylids in cattle, horses and camels, and Eimeriids in cattle and small ruminants. Eimeria spp. were the most prevalent parasite particularly in small ruminants. The relationship between Eimeria infection and management in small ruminant farms was discussed. PMID:26012220

  10. Assessing skin sensitization hazard in mice and men using non-animal test methods.

    PubMed

    Urbisch, Daniel; Mehling, Annette; Guth, Katharina; Ramirez, Tzutzuy; Honarvar, Naveed; Kolle, Susanne; Landsiedel, Robert; Jaworska, Joanna; Kern, Petra S; Gerberick, Frank; Natsch, Andreas; Emter, Roger; Ashikaga, Takao; Miyazawa, Masaaki; Sakaguchi, Hitoshi

    2015-03-01

    Sensitization, the prerequisite event in the development of allergic contact dermatitis, is a key parameter in both hazard and risk assessments. The pathways involved have recently been formally described in the OECD adverse outcome pathway (AOP) for skin sensitization. One single non-animal test method will not be sufficient to fully address this AOP and in many cases the use of a battery of tests will be necessary. A number of methods are now fully developed and validated. In order to facilitate acceptance of these methods by both the regulatory and scientific communities, results of the single test methods (DPRA, KeratinoSens, LuSens, h-CLAT, (m)MUSST) as well for a the simple '2 out of 3' ITS for 213 substances have been compiled and qualitatively compared to both animal and human data. The dataset was also used to define different mechanistic domains by probable protein-binding mechanisms. In general, the non-animal test methods exhibited good predictivities when compared to local lymph node assay (LLNA) data and even better predictivities when compared to human data. The '2 out of 3' prediction model achieved accuracies of 90% or 79% when compared to human or LLNA data, respectively and thereby even slightly exceeded that of the LLNA. PMID:25541156

  11. Biodistribution studies of polymeric nanoparticles for drug delivery in mice.

    PubMed

    Falzarano, Maria Sofia; Bassi, Elena; Passarelli, Chiara; Braghetta, Paola; Ferlini, Alessandra

    2014-11-01

    Abstract Duchenne muscular dystrophy (DMD) is a severe hereditary neuromuscular disorder caused by mutations in the dystrophin gene. Antisense-mediated targeted exon skipping has been shown to restore dystrophin expression both in DMD patients and in the mdx mouse, the murine model of DMD, but the ineffective delivery of these molecules limits their therapeutic use. We demonstrated that PMMA/N-isopropil-acrylamide (ZM2) nanoparticles (NPs), administered both intraperitoneally and orally, were able to deliver 2'OMePS antisense inducing various extents of dystrophin restoration in the mdx mice. Defining NP biodistribution is crucial to improve effects on target and dose regimens; thus, we performed in vivo studies of novel ZM4 NPs. ZM4 are conjugated with NIR fluorophores as optical probes suitable for studies on the Odyssey Imaging System. Our results indicate that NPs are widely distributed in all body muscles, including skeletal muscles and heart, suggesting that these vehicles are appropriate to deliver antisense oligonucleotides for targeting striated muscles in the DMD animal model, thus opening new horizons for Duchenne therapy. PMID:25244215

  12. Biodistribution Studies of Polymeric Nanoparticles for Drug Delivery in Mice

    PubMed Central

    Falzarano, Maria Sofia; Bassi, Elena; Passarelli, Chiara; Braghetta, Paola

    2014-01-01

    Abstract Duchenne muscular dystrophy (DMD) is a severe hereditary neuromuscular disorder caused by mutations in the dystrophin gene. Antisense-mediated targeted exon skipping has been shown to restore dystrophin expression both in DMD patients and in the mdx mouse, the murine model of DMD, but the ineffective delivery of these molecules limits their therapeutic use. We demonstrated that PMMA/N-isopropil-acrylamide (ZM2) nanoparticles (NPs), administered both intraperitoneally and orally, were able to deliver 2′OMePS antisense inducing various extents of dystrophin restoration in the mdx mice. Defining NP biodistribution is crucial to improve effects on target and dose regimens; thus, we performed in vivo studies of novel ZM4 NPs. ZM4 are conjugated with NIR fluorophores as optical probes suitable for studies on the Odyssey Imaging System. Our results indicate that NPs are widely distributed in all body muscles, including skeletal muscles and heart, suggesting that these vehicles are appropriate to deliver antisense oligonucleotides for targeting striated muscles in the DMD animal model, thus opening new horizons for Duchenne therapy. PMID:25244215

  13. Effect of Paclitaxel on Antitumor Activity of Cyclophosphamide: Study on Two Transplanted Tumors in Mice.

    PubMed

    Kaledin, V I; Nikolin, V P; Popova, N A; Pyshnaya, I A; Bogdanova, L A; Morozkova, T S

    2015-11-01

    Antitumor effect of paclitaxel used as the monotherapy or in combination with cyclophosphamide was studied on CBA/LacSto mice with transplanted LS and RLS tumors characterized by high (LS) and low (RLS) sensitivity to cyclophosphamide. The therapeutic effects of cyclophosphamide and paclitaxel were summed in animals with drug-resistant RLS tumor, while combined use of these drugs in LS tumor highly sensitive to the apoptogenic effect of cyclophosphamide was no more effective than cyclophosphamide alone. PMID:26597686

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

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    2005-01-01

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

  15. The Potential of Adaptive Design in Animal Studies.

    PubMed

    Majid, Arshad; Bae, Ok-Nam; Redgrave, Jessica; Teare, Dawn; Ali, Ali; Zemke, Daniel

    2015-01-01

    Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research. PMID:26473839

  16. The Potential of Adaptive Design in Animal Studies

    PubMed Central

    Majid, Arshad; Bae, Ok-Nam; Redgrave, Jessica; Teare, Dawn; Ali, Ali; Zemke, Daniel

    2015-01-01

    Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research. PMID:26473839

  17. Radioprotectors and Tumors: Molecular Studies in Mice

    SciTech Connect

    Gayle Woloschak, David Grdina

    2010-03-10

    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

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

    PubMed

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

    2013-02-01

    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

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

    PubMed Central

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

    2014-01-01

    Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria. PMID:25048459

  20. a Study of Sasin-Animal Sky Map on Chonmunryucho

    NASA Astrophysics Data System (ADS)

    Yang, Hong-Jin; Park, Myeong-Gu

    2003-03-01

    Chon-Mun-Ryu-Cho, written (edited) by Lee Sun-Ji during the period of King Se-Jong, is a representative astronomy book of Cho-Sun (A.D. 1392 -1910) Dynasty. We find and study in the first page of the book; the description of 28 oriental constellations as a Sasin (four mythical oriental animals)-animal sky map which is not widely known yet. The map consists of four groups of constellations, each of which represents the Sasin: Chang-Ryong (dragon), Baek-Ho (tigers with Ki-Rin [Oriental giraffe]), Ju-Jak (Chinese phoenix), Hyun-Mu (a tortoise interwined with a snake). Each group (animals) spans 2˜7 of 28 oriental constellations As we know from the illustration of the Chon-Sang-Yol-Cha-Bun-Ya-Ji-Do a representative sky map of Cho-Sun Dynasty, astronomy in Cho-Sun Dynasty is closely related to that in Go-Gu-Ryer (B.C. 37 -A.D. 668) Dynasty. Since these Sasin-animals appear in most mural paintings of Go-Gu-Ryer tombs, visualization of sky with these animal constellations could have been established as early as in Go-Gu-Ryer Dynasty. We also reconstruct this ''A Sasin-animal Korean sky map'' based on the shapes of the Sasin and Ki-Rin from Go-Gu-Ryer paintings and 28 oriental constellations in Chon-Sang-Yol-Cha-Bun-Ya-Ji-Do.

  1. Nitrobenzene potential human cancer risk based on animal studies.

    PubMed

    Holder, J W

    1999-08-01

    Inhaled nitrobenzene (NB) in animals produces cancer at eight sites in three rodent strains. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, and F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley male rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN) in the cecum by bacteria and in the body by the microsomes. In reduction, NB first forms the nitroanion free radical, which can react with O2 to form O2*-. Repeated NB dosing produces a persistent redox couple NOB<==>PH in red blood cells that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. The cancer hazard evaluation of NB is that it is a probable human carcinogen by any route of exposure. The maximum response is in F344/N male rats which is used for dose-response modelling. The model to estimate the upper 95% confidence limit (UCL95%) of NB human carcinogenicity is a no-threshold, linear low-dose, and multistaged animal model (LMS). The UCL95% of cancer slope is estimated to be 0.11(6) mg/kg/day (mkd). At de minimus risk (1:10(6)), the virtually safe dose (VSD) is estimated to be 9.1 ng/kg/day (nkd). PMID:10487356

  2. Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

    PubMed Central

    Yeh, Shuyuan; Tsai, Meng-Yin; Xu, Qingquan; Mu, Xiao-Min; Lardy, Henry; Huang, Ko-En; Lin, Hank; Yeh, Shauh-Der; Altuwaijri, Saleh; Zhou, Xinchang; Xing, Lianping; Boyce, Brendan F.; Hung, Min-Chi; Zhang, Su; Gan, Lin; Chang, Chawnshang

    2002-01-01

    By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice. PMID:12370412

  3. Chimeric Mice with Humanized Liver: Tools for the Study of Drug Metabolism, Excretion, and Toxicity

    PubMed Central

    Strom, Stephen C.; Davila, Julio; Grompe, Markus

    2011-01-01

    Recent developments in animal models have allowed the creation of mice with genetic alterations that cause hepatocyte damage that results, over time, in the loss of native hepatocytes. If donor, human hepatocytes are transplanted into these animals, they repopulate the host liver, frequently replacing over 70% of the native liver with human cells. Immunodeficient mice that overexpress urokinase-type plasminogen activator (uPA) and, alternatively, with a knockout of the fumarylacetoacetate hydrolase (Fah) genes are the two most common mouse models for these studies. These mice are called chimeric or “humanized” because the liver is now partially repopulated with human cells. In this report we will review the published work with respect to Phase I and Phase II metabolic pathways and the expression of hepatic transport proteins. While the studies are still at the descriptive stage, it is already clear that some humanized mice display high levels of repopulation with human hepatocytes, express basal and inducible human CYP450 genes, and human conjugation and hepatic transport pathways. When the strengths and weaknesses of these humanized mouse models are fully understood, they will likely be quite valuable for investigations of human liver-mediated metabolism and excretion of drugs and xenobiotics, drug–drug interactions, and for short- and long-term investigation of the toxicity of drugs or chemicals with significant human exposure. PMID:20645070

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

    PubMed Central

    Tang, Yu-xiao; Yu, Sheng-qiang; Jin, Shao-hua; Meng, Xiao-mei; Li, Hua-feng; Liu, Fu-jun; Sun, Qiang; Wang, Hai-yan; Li, Jian-yuan

    2014-01-01

    Background Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs), a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs) differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID)/non-obese diabetic (NOD) mice, an animal model of diabetes. Methods We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5–7×106 differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n = 20). The control group were transplanted with undifferentiated hESCs (n = 6). Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels. Results The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature β cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ≥8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001). Conclusions The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct hyperglycemia in SCID/NOD mice for ≥8 weeks. PMID:25009980

  5. Childhood Cruelty to Animals: A Tri-National Study

    ERIC Educational Resources Information Center

    Mellor, David; Yeow, James; Hapidzal, Noor Fizlee Mohd; Yamamoto, Takashi; Yokoyama, Akimitsu; Nobuzane, Yosuke

    2009-01-01

    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…

  6. A Small Scale Experimental Study: Using Animations to Learn Vocabulary

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  7. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient. PMID:9644328

  8. Animal venom studies: Current benefits and future developments

    PubMed Central

    Utkin, Yuri N

    2015-01-01

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensive methods allows studying either of venoms available in tiny amounts or of low abundant components in already known venoms. PMID:26009701

  9. Animal venom studies: Current benefits and future developments.

    PubMed

    Utkin, Yuri N

    2015-05-26

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensive methods allows studying either of venoms available in tiny amounts or of low abundant components in already known venoms. PMID:26009701

  10. Safety studies of post-surgical buprenorphine therapy for mice.

    PubMed

    Traul, Karl A; Romero, Jennell B; Brayton, Cory; DeTolla, Louis; Forbes-McBean, Nadine; Halquist, Matthew S; Karnes, H Thomas; Sarabia-Estrada, Rachel; Tomlinson, Michael J; Tyler, Betty M; Ye, Xiaobu; Zadnik, Patricia; Guarnieri, Michael

    2015-04-01

    The use of appropriate analgesia in laboratory mice may be suboptimal because of concerns about adverse events (AE). Target Animal Safety trials were conducted to determine the safety of an extended-release suspension of buprenorphine. Drug or control suspensions were injected subcutaneously in surgically-treated BALB/c mice anesthetized with ketamine-xylazine to mimic post-operative conditions in which the compound might commonly be administered. Single and repeat five-fold (5×) excesses of the 3.25 mg/kg intended dose were used to provoke potential AE. Trials included prospective measurements of weight changes, blood chemistry, hematology, and histopathology. Clinical and histopathology findings were similar in drug-treated and control mice in a four-day trial using a single 16.25 mg/kg, 5× overdose of the drug. In a 12-day trial, which used a total buprenorphine dose of 48.75 mg/kg, clinical and histopathology values were also similar in control and drug-treated female mice. In the male arm of the repeat-overdose trial, two of eight mice died on the morning of day 12, three days following the third 16.25 mg/kg overdose administration. Histopathology did not reveal a cause of death. In a 14-month trial using a single 3.25 mg/kg dose of the drug, no significant findings identified potential AE. These findings indicate a high tolerance to an extended-release buprenorphine suspension administered post-operatively in mice with appropriate husbandry. PMID:25305141

  11. [Using spectra and visual modeling to study animal coloration].

    PubMed

    Yang, Can-Chao; Liang, Wei

    2013-12-01

    Animal coloration has many adaptive functions and plays an important role in signal communication both among intra- and interspecies. For example, it has been widely used in mate choice, intrasexual competition, and as aposematic or cryptic coloration in predator avoidance. Many colors and pigments also function in microbial resistance, structural support, photoprotection, and thermoregulation. Differing from human vision, based on RGB system, many other animals have tetrachromatic vision system, which includes the ultraviolet (UV) range that is undetectable by human eyes. Previous studies showed that ultraviolet is important in some species' social signaling and communication. Moreover, cone inner segments of most classes of vertebrate contain an oil droplet, which acts as a cut-off filter absorbing wavelengths below a critical value, and transmitting longer wavelengths. Animal and human vision is significantly different in that the classification of color by human standards may be a misleading for measuring animal coloration. Here, we illuminate how to use fiber spectrophotometer to quantify animal coloration, and analyze it by spectra analysis and visual modeling. As an example, we obtained plumage reflectance spectra from male and female scarlet minivets (Pericrocotus flammeus). This bird species is sexually dimorphic that the males have plumage color in black and red, while the females have grey and yellow accordingly. These plumage colors are typically generated from melanin and carotenoid pigments, which have an effect on antioxidant activity. Analysis of spectra segments provides hue, chroma, brightness and relative brightness of each wave range. Visual modeling maps color patches on tetrahedral color space and Robinson projection, meanwhile, calculates color span and color space volume which describe the color contrast and color diversity, respectively. In visual modeling, ambient light irradiance and spectral sensitivity of animal retinas are included, which provides an objective evaluation of coloration of animal vision. PMID:24415688

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

    PubMed Central

    2014-01-01

    Background This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. Methods A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. Results The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 μg/kgBW (95% CI: 383–535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 μg/kgBW (95% CI: 362–566) and 447 μg/kgBW (95% CI: 378–504 μg/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 μg/kgBW (95% CI: 442–517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Conclusion Optimised RSP design reduces the number of animals needed. The design converges rapidly on the area of interest and is at least as efficient as both the UDPs and RW design. PMID:24661560

  13. Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness

    PubMed Central

    O’Callaghan, James P.; Kelly, Kimberly A.; Locker, Alicia R.; Miller, Diane B.; Lasley, Steve M.

    2016-01-01

    Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of persistent sickness behavior. Among conditions encountered in the Gulf War (GW) theater were physiological stressors (e.g., heat/cold/physical activity/sleep deprivation), prophylactic treatment with the reversible AChE inhibitor, pyridostigmine bromide (PB), the insect repellent, N, N-diethyl-meta-toluamide (DEET), and potentially the nerve agent, sarin. Prior exposure to the anti-inflammatory glucocorticoid, corticosterone (CORT), at levels associated with high physiological stress, can paradoxically prime the CNS to produce a robust proinflammatory response to neurotoxicants and systemic inflammation; such neuroinflammatory effects can be associated with sickness behavior. Here, we examined whether CORT primed the CNS to mount neuroinflammatory responses to GW exposures as a potential model of GWI. Male C57BL/6 mice were treated with chronic (14 days) PB/DEET, subchronic (7–14 days) CORT, and acute exposure (day 15) to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. DFP alone caused marked brain-wide neuroinflammation assessed by qPCR of tumor necrosis factor-α, IL6, chemokine (C-C motif) ligand 2, IL-1β, leukemia inhibitory factor, and oncostatin M. Pre-treatment with high physiological levels of CORT greatly augmented (up to 300-fold) the neuroinflammatory responses to DFP. Anti-inflammatory pre-treatment with minocycline suppressed many proinflammatory responses to CORT+DFP. Our findings are suggestive of a possible critical, yet unrecognized interaction between the stressor/environment of the GW theater and agent exposure(s) unique to this war. Such exposures may in fact prime the CNS to amplify future neuroinflammatory responses to pathogens, injury, or toxicity. Such occurrences could potentially result in the prolonged episodes of sickness behavior observed in GWI. PMID:25753028

  14. [Experimental studies with mice on the program of the biosatellite BION-M1 mission].

    PubMed

    Andreev-Andrievsky, A A; Shenkman, B S; Popova, A S; Dolguikh, O N; Anokhin, K V; Soldatov, P E; Ilyin, E A; Sychev, V N

    2014-01-01

    Purpose of the BION-M1 project was laying the evidence and technological basis for addressing the medical issues of future remote space exploration missions by humans. The program of researches with the use of mice was focused on elicitation of cellular and molecular mechanisms of the muscular, cardiovascular and immune reactions to extended exposure in microgravity. The comprehensive studies combined lifetime measurements with investigations of mice tissues and cells by dint of the cutting-edge morphological, biochemical and molecular biology techniques. Males of mice C57/BL6 aged 4 to 5 months were chosen as the object of studies. They were distributed into the flight, ground control and two vivarium (laboratory control) groups and investigated immediately on return and after 7 days of readaptation. Some of the physiological functions were recorded throughout the flight. To ensure wellbeing of the animals in the experiments and to enhance data quality, prior to launch the mice were specially trained so as to accommodate to the group living, eating space food, and in-flight stress factors. Those of the mice that were designated for lifetime investigations were tested and received training pre-launch. PMID:25033610

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

    PubMed Central

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

    2014-01-01

    In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals. PMID:24855386

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

    PubMed

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

    2014-01-01

    In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal-dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals. PMID:24855386

  17. Pharmaco-EEG Studies in Animals: A History-Based Introduction to Contemporary Translational Applications.

    PubMed

    Drinkenburg, Wilhelmus H I M; Ahnaou, Abdallah; Ruigt, Gé S F

    2015-01-01

    Current research on the effects of pharmacological agents on human neurophysiology finds its roots in animal research, which is also reflected in contemporary animal pharmaco-electroencephalography (p-EEG) applications. The contributions, present value and translational appreciation of animal p-EEG-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. After the pioneering years in the late 19th and early 20th century, animal p-EEG research flourished in the pharmaceutical industry in the early 1980s. However, around the turn of the millennium the emergence of structurally and functionally revealing imaging techniques and the increasing application of molecular biology caused a temporary reduction in the use of EEG as a window into the brain for the prediction of drug efficacy. Today, animal p-EEG is applied again for its biomarker potential - extensive databases of p-EEG and polysomnography studies in rats and mice hold EEG signatures of a broad collection of psychoactive reference and test compounds. A multitude of functional EEG measures has been investigated, ranging from simple spectral power and sleep-wake parameters to advanced neuronal connectivity and plasticity parameters. Compared to clinical p-EEG studies, where the level of vigilance can be well controlled, changes in sleep-waking behaviour are generally a prominent confounding variable in animal p-EEG studies and need to be dealt with. Contributions of rodent pharmaco-sleep EEG research are outlined to illustrate the value and limitations of such preclinical p-EEG data for pharmacodynamic and chronopharmacological drug profiling. Contemporary applications of p-EEG and pharmaco-sleep EEG recordings in animals provide a common and relatively inexpensive window into the functional brain early in the preclinical and clinical development of psychoactive drugs in comparison to other brain imaging techniques. They provide information on the impact of drugs on arousal and sleep architecture, assessing their neuropharmacological characteristics in vivo, including central exposure and information on kinetics. In view of the clear disadvantages as well as advantages of animal p-EEG as compared to clinical p-EEG, general statements about the usefulness of EEG as a biomarker to demonstrate the translatability of p-EEG effects should be made with caution, however, because they depend on the particular EEG or sleep parameter that is being studied. The contribution of animal p-EEG studies to the translational characterisation of centrally active drugs can be furthered by adherence to guidelines for methodological standardisation, which are presently under construction by the International Pharmaco-EEG Society (IPEG). PMID:26901675

  18. Intestinal microflora of deep-sea animals: a taxonomic study

    NASA Astrophysics Data System (ADS)

    Oliver, James D.; Smith, J. Edward

    1982-06-01

    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.

  19. An Exploratory Study of Apache Middle School Students' Computer Animation.

    ERIC Educational Resources Information Center

    Stokrocki, Mary; Buckpitt, Marcia

    The paper describes a participant observation study of a 3 week summer art program for Apache middle school students on the White Mountain Reservation. Computer art skills, specifically animation using a menu-driven computer paint program, were the focus of the investigation. Because it was in the context of a summer program, instruction was…

  20. [The study and manufacture of spinning counter for experimental animals].

    PubMed

    Qi, X P; Zhou, C; Liu, F J; Chen, Z; Jiang, L; Yan, Z

    1997-09-01

    The single-chip microcomputer technique is used in the present study of spinning counter, which has 4 observation tunnels, the spinning behave of four experiment animals can be recorded at same time. The function of this instrument has four selections according to different experiment, and the recording data can be compute processed. PMID:11189275

  1. Field Research Studying Whales in an Undergraduate Animal Behavior Laboratory

    ERIC Educational Resources Information Center

    MacLaren, R. David; Schulte, Dianna; Kennedy, Jen

    2012-01-01

    This work describes a new field research laboratory in an undergraduate animal behavior course involving the study of whale behavior, ecology and conservation in partnership with a non-profit research organization--the Blue Ocean Society for Marine Conservation (BOS). The project involves two weeks of training and five weekend trips on whale watch…

  2. A novel inhalation challenge set to study animal model of allergic alveolitis.

    PubMed

    Golec, Marcin; Skórska, Czesława; Lemieszek, Marta; Dutkiewicz, Jacek

    2009-01-01

    A novel inhalation challenge set for the study of experimental allergic alveolitis (hypersensitivity pneumonitis) in mice was designed. A finely dispersed aerosol of allergenic extract generated by the commercial ultrasonic nebulizer "TAJFUN MU1" (produced by Medbryt, Warsaw, Poland) was transported to the airtight inhalation chamber. In the chamber were placed 15 perforated containers made of transparent plastic, each containing one mouse. They were coupled in 3 units, each consisted of 5 containers. The constant flow of aerosol through the chamber was assured by commercial vacuum pump "PL 2/3" (AGA LABOR S.C., Warsaw, Poland). The applied set enabled the natural exposure of mice via the inhalation route to known quantities of allergen (usually microbial) suspended in saline, and then dispersed in form of fine aerosol by ultrasonic nebulizer. This method assures the penetration of allergen into the deep parts of lungs, alveoli and bronchioli. The detailed study of histopathological and biochemical changes in the lungs of exposed animals will be the subject of further publications. So far, the retention of endotoxin in the lungs of mice exposed to the extract of a Gram-negative bacterium Pantoea agglomerans and appearance of positive serologic reactions to this extract indicate the effectiveness of the method. PMID:19572490

  3. Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.

    PubMed

    Brehm, Michael A; Powers, Alvin C; Shultz, Leonard D; Greiner, Dale L

    2012-05-01

    Despite decades of studying rodent models of type 1 diabetes (T1D), no therapy capable of preventing or curing T1D has successfully been translated from rodents to humans. This inability to translate otherwise promising therapies to clinical settings likely resides, to a major degree, from significant species-specific differences between rodent and human immune systems as well as species-related variances in islets in terms of their cellular composition, function, and gene expression. Indeed, taken collectively, these differences underscore the need to define interactions between the human immune system with human ? cells. Immunodeficient mice engrafted with human immune systems and human ? cells represent an interesting and promising opportunity to study these components in vivo. To meet this need, years of effort have been extended to develop mice depleted of undesirable components while at the same time, allowing the introduction of constituents necessary to recapitulate physiological settings as near as possible to human T1D. With this, these so-called "humanized mice" are currently being used as a preclinical bridge to facilitate identification and translation of novel discoveries to clinical settings. PMID:22553498

  4. Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness.

    PubMed

    O'Callaghan, James P; Kelly, Kimberly A; Locker, Alicia R; Miller, Diane B; Lasley, Steve M

    2015-06-01

    Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of persistent sickness behavior. Among conditions encountered in the Gulf War (GW) theater were physiological stressors (e.g., heat/cold/physical activity/sleep deprivation), prophylactic treatment with the reversible AChE inhibitor, pyridostigmine bromide (PB), the insect repellent, N,N-diethyl-meta-toluamide (DEET), and potentially the nerve agent, sarin. Prior exposure to the anti-inflammatory glucocorticoid, corticosterone (CORT), at levels associated with high physiological stress, can paradoxically prime the CNS to produce a robust proinflammatory response to neurotoxicants and systemic inflammation; such neuroinflammatory effects can be associated with sickness behavior. Here, we examined whether CORT primed the CNS to mount neuroinflammatory responses to GW exposures as a potential model of GWI. Male C57BL/6 mice were treated with chronic (14 days) PB/ DEET, subchronic (7-14 days) CORT, and acute exposure (day 15) to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. DFP alone caused marked brain-wide neuroinflammation assessed by qPCR of tumor necrosis factor-α, IL6, chemokine (C-C motif) ligand 2, IL-1β, leukemia inhibitory factor, and oncostatin M. Pre-treatment with high physiological levels of CORT greatly augmented (up to 300-fold) the neuroinflammatory responses to DFP. Anti-inflammatory pre-treatment with minocycline suppressed many proinflammatory responses to CORT+DFP. Our findings are suggestive of a possible critical, yet unrecognized interaction between the stressor/environment of the GW theater and agent exposure(s) unique to this war. Such exposures may in fact prime the CNS to amplify future neuroinflammatory responses to pathogens, injury, or toxicity. Such occurrences could potentially result in the prolonged episodes of sickness behavior observed in GWI. Gulf War (GW) veterans were exposed to stressors, prophylactic medicines and, potentially, nerve agents in theater. Subsequent development of GW Illness, a persistent multi-symptom disorder with features characteristic of sickness behavior, may be caused by priming of the CNS resulting in exaggerated neuroinflammatory responses to pathogens/insults. Nerve agent, diisopropyl fluorophosphate (DFP), produced a neuroinflammatory response that was exacerbated by pre-treatment with levels of corticosterone simulating heightened stressor conditions. While prophylactic treatments reduced DFP-induced neuroinflammation, this effect was negated when those treatments were combined with corticosterone. PMID:25753028

  5. Blood compatible microfluidic system for pharmacokinetic studies in small animals.

    PubMed

    Convert, Laurence; Baril, Frdrique Girard; Boisselle, Vincent; Pratte, Jean-Franois; Fontaine, Rjean; Lecomte, Roger; Charette, Paul G; Aimez, Vincent

    2012-11-21

    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

  6. Animal mdels for the study of the effects of spaceflight on the immune system

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, G.

    Animal models have been used extensively to study the effects of spaceflight on the immune system. The rat has been the animal used most extensively, but some studies have also been carried out utilizing mice and rhesus monkeys. Hindlimb unloading of rats and mice is a ground-based model that has been utilized to determine the effects of spaceflight-type conditions on the immune systems. The results using this model have shown that hindlimb unloading results in alterations of functional rodent immune responses, including cytokine production, blastogenesis of leukocytes, response of bone marrow cells to colony stimulating factors, neutrophil activity, and resistance to infection. Distribution of leukocyte subtypes was not affected by hindlimb unloading. Studies on rats flown in space have demonstrated that exposure to spaceflight results in alterations in cytokine production, alterations in the ability of bone marrow cells to respond to colony stimulating factors, alterations in leukocyte subset distribution, and alterations in natural killer cell function. When pregnant rats were flown in space, although the immune responses of the pregnant mothers were altered by exposure to spaceflight, no effects of spaceflight on the immune responses of the offspring were observed. In one study, rhesus monkeys were flown in space and their immune status was evaluated upon their return to earth. Results of that study showed alterations in the ability of monkey immune cells to produce cytokines, express cytokine receptors, and respond to colony stimulating factor. Therefore, it is clear that exposure to spaceflight results in alterations in immune responses of the test animals. These changes are similar to those observed for humans that have flown in space, and demonstrate that the animal models are appropriate for studying the effects of spaceflight on the immune system. Although use of the hindlimb unloading model on the ground has indicated that exposure to the model also results in alterations in resistance to infection, there have been no spaceflight studies using animal models to determine if exposure to spaceflight conditions alters actual resistance to infection or to tumors. This possibility should be the subject of future studies. The US National Aeronautics and Space Administration ( ASA) supported studies described above by direct grantN support and through NASA Cooperative Agreement NCC 9 58 with the National- Space Biomedical Research Institute.

  7. An anesthetic method compatible with 18F-FDG-PET studies in mice

    PubMed Central

    Siikanen, Jonathan; Sjövall, Johanna; Forslid, Anders; Brun, Eva; Bjurberg, Maria; Wennerberg, Johan; Ekblad, Lars; Sandell, Anders

    2015-01-01

    The purpose of this study was to establish an experimental setting and an anesthetic method compatible with future sequential studies using 18F-FDG-PET single scans, i.e. autoradiographic measurements, for the estimation of metabolic rate of glucose (MRglc) in mice. In this study we had no access to a small animal PET scanner and therefore focus was on the anesthetic setting and optimization of the input function as a preparation for the future tumor metabolic studies. Initially, four combinations of intraperitoneal (ip) anesthesia were tested on tumor bearing mice. Fentanyl-fluanisone plus diazepam yielded low and stable blood glucose levels and kept the animals sedated for approximately 2 h. The anesthesia was also tested in a longitudinal 18F-FDG study, where tumor bearing mice were anesthetized, injected with 18F-FDG, and sampled for blood, before, one day after, and 8 days after treatment with cisplatin. The animals were in good condition during the entire study period. To validate the method, average MRglc of whole brain and cerebellum in mice were calculated and compared with the literature. The average MRglc in the whole brain and cerebellum were 46.2±4.4 and 39.0±3.1 µmol 100g-1 min-1. In the present study, we have shown that an ip anesthesia with a combination of fentanyl-fluanisone and diazepam is feasible and provides stable and low blood glucose levels after a fasting period of 4 h in experiments in nude mice with xenografted human tumors. We have also verified that 18F-FDG, intraperitoneally administrated, results in an expected plasma activity uptake and clearance. The method doesn’t alter the uptake in brain which is an indirect indication that the anesthesia doesn’t alter the uptake in other organs. In combination with meticulous animal handling this set-up is reliable and future sequential tumor studies of early metabolic effects with calculation of MRglc following cytotoxic therapy are made possible. PMID:26069860

  8. Vermectomy enhances parvalbumin expression and improves motor performance in weaver mutant mice: an animal model for cerebellar ataxia.

    PubMed

    Grüsser-Cornehls, U; Grüsser, C; Bäurle, J

    1999-01-01

    In the Weaver mutant mouse (wv/wv), an animal model for hereditary cerebellar ataxia, electrophysiological experiments have revealed a disorganized output of cerebellar Purkinje cells (the latter using GABA as an inhibitory transmitter) which, by a cascade of mechanisms, was thought to be the cause of the poor motor abilities. In Purkinje cell degeneration mice (pcd/pcd) lacking nearly all Purkinje cells and displaying milder motor deficiencies than wv, in comparison to wild-type mice, a strong increase in parvalbumin- and (co-localized with parvalbumin) glycine-immunopositive somata in the deep cerebellar and vestibular nuclei has recently been found. It was therefore intriguing to investigate whether motor performance in weaver mutants could be ameliorated by applying cerebellar lesions to eliminate the faulty output and to look for a change in transmitter weighting, indicated by a strong increase in parvalbumin-positive somata in areas (the respective target areas) which were formerly devoid of it. Ten Weaver mutants were subjected to cerebellar lesions. After removal of the vermis a total abolition of tremor, a definite improvement in the balance of affected body parts, an increase in locomotor activity when tested in an open-field matrix, and a strong increase in parvalbumin expression in Weaver mutant deep cerebellar and vestibular nuclei in comparison to wild-types have indeed been found. Increase in motor activity (or explorative behaviour) has been placed in relation to learning mechanisms. The increase in parvalbumin expression and the observed improvement in motor abilities and mechanisms probably related to learning underline the hypothesis that any change in the physiological equilibrium of the brain function by removal of input or output related to an assembly of nerve cells leads to a cascade of changes at the transmitter and neuronal level in near or distant connected brain structures. PMID:10336081

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

    PubMed

    Shinoda, Yo; Sadakata, Tetsushi; Furuichi, Teiichi

    2013-01-01

    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

  10. The use of transgenic animals to study lipoprotein metabolism

    SciTech Connect

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

    1993-12-01

    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.

  11. High Field Small Animal Magnetic Resonance Oncology Studies

    PubMed Central

    Bokacheva, Louisa; Ackerstaff, Ellen; LeKaye, H. Carl; Zakian, Kristen; Koutcher, Jason A.

    2014-01-01

    This review focuses on the applications of high magnetic field magnetic resonance imaging (MRI) and spectroscopy (MRS) to cancer studies in small animals. High field MRI can provide information about tumor physiology, the microenvironment, metabolism, vascularity and cellularity. Such studies are invaluable for understanding tumor growth and proliferation, response to treatment and drug development. The MR techniques reviewed here include 1H, 31P, Chemical Exchange Saturation Transfer (CEST) imaging, and hyperpolarized 13C MR spectroscopy as well as diffusion-weighted, Blood Oxygen Level Dependent (BOLD) contrast imaging, and dynamic contrast-enhanced MR imaging. These methods have been proven effective in animal studies and are highly relevant to human clinical studies. PMID:24374985

  12. Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.

    PubMed

    Streck, Emilio L; Scaini, Giselli; Jeremias, Gabriela C; Rezin, Gislaine T; Gonçalves, Cinara L; Ferreira, Gabriela K; Réus, Gislaine Z; Resende, Wilson R; Valvassori, Samira S; Kapczinski, Flávio; Andersen, Mônica L; Quevedo, João

    2015-06-01

    There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania. PMID:25894682

  13. Social fear conditioning: a novel and specific animal model to study social anxiety disorder.

    PubMed

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

    2012-05-01

    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. PMID:22237310

  14. Immunotoxicology of arc welding fume: Worker and experimental animal studies

    PubMed Central

    Zeidler-Erdely, Patti C.; Erdely, Aaron; Antonini, James M.

    2015-01-01

    Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses. PMID:22734811

  15. Narcosis studies and oxygen poisoning of mice

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The research for a mechanism by which narcotic gases alter metabolism is reported. Possible sites of action by narcotic and anesthetic gases in isolated electron transport particles were explored. Using the relative activities of the NADH-oxygen, NADH-ferricyanide, succinate-cytochrome C and succinate-NAD oxidoreductase systems as parameters, the relative potency of volatile anesthetics were tested. Testing the relative ability of human subjects to contract and repay an oxygen debt while in the narcotic versus alert state, it was found that narcosis induced by 33% nitrous oxide increased the size of the oxygen debt contracted and the amount of oxygen required to repay it during recovery. Mice acclimatized to sea level (760 mm Hg), 5000 feet (632 mm Hg) or 15,000 feet 437 mm Hg) for from one to eight weeks were found to be more susceptible to convulsion and death as a function of altitude acclimatization when tested in hyperoxic environments. There were no reasonable explanations for the connection between hypoxia and oxygen poisoning but several practical implications for persons living at altitude are discussed.

  16. Transgenic animal models of neurodegeneration based on human genetic studies

    PubMed Central

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

    2011-01-01

    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. PMID:20931247

  17. Reproduction in the space environment: Part I. Animal reproductive studies

    NASA Technical Reports Server (NTRS)

    Santy, P. A.; Jennings, R. T.; Craigie, D.

    1990-01-01

    Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.

  18. The Pleurodele, an animal model for space biology studies

    NASA Astrophysics Data System (ADS)

    Gualandris, L.; Grinfeld, S.; Foulquier, F.; Kan, P.; Duprat, A. M.

    Pleurodeles waltl, an Urodele amphibian is proposed as a model for space biology studies. Our laboratory is developing three types of experiments in space using this animal: 1) in vivo fertilization and development (``FERTILE'' project); 2) influence of microgravity and space radiation on the organization and preservation of spacialized structures in the neurons and muscle cells (in vitro; ``CELIMENE'' PROJECT); 3) influence of microgravity on tissue regeneration (muscle, bone, epidermis and spinal cord).

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

    PubMed

    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

    2012-06-01

    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-α 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 μL of saline intra-implant; (2) treated group-sixteen mice injected with 0.5 μg/30 μL 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-β-D glucosaminidase) and levels of the cytokines, TNF-α 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

  20. Carcinogenesis studies of benzophenone in rats and mice

    PubMed Central

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

    2007-01-01

    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. PMID:17187913

  1. Studies on the interaction between ethanol and two industrial solvents (methyl isobutyl ketone) in mice

    SciTech Connect

    Granvil, C.P.; Sharkawi, M.; Plaa, G.L. )

    1991-03-11

    Methyl n-butyl ketone (MnBK) and methyl isobutyl ketone (MiBK) prolong the duration of ethanol-induced loss of righting reflex (EILRR) in mice. MnBK was almost twice as potent in this regard. To explain this difference, the metabolism of both ketones was studied in male CD-1 mice using GC. MiBK was converted to 4-methyl-2-pentanol (4MPOL) and 4-hydroxy methyl isobutyl ketone (HMP). MnBK metabolites were 2-hexanol (2HOL) and 2,5-hexanedione (2,5HD). The effects of both ketones and metabolites on EILRR and ethanol (E) elimination were studied in mice. The ketones and their metabolites were dissolved in corn oil and injected intraperitoneally 30 min before E 4g/kg for EILRR and 2g/kg for E elimination. In the following doses: MnBK, 5; MiBK, 5; 2HOL, 2.5; 4MPOL, 2.5; and HMP 2.5, significantly prolonged EILRR. Concentrations of E in blood and brain upon return of the righting reflex were similar in solvent-treated and control animals. The mean elimination rate of E was slower in groups given MnBK or 2HOL than in control animals. No change in E elimination was observed with MiBK, HMP, 4MPOL, or 2, 5HD.

  2. A Simple Guide Screw Method for Intracranial Xenograft Studies in Mice

    PubMed Central

    Donoghue, Jacqueline F.; Bogler, Oliver; Johns, Terrance G.

    2011-01-01

    The grafting of human tumor cells into the brain of immunosuppressed mice is an established method for the study of brain cancers including glioblastoma (glioma) and medulloblastoma. The widely used stereotactic approach only allows for the injection of a single animal at a time, is labor intensive and requires highly specialized equipment. The guide screw method, initially developed by Lal et al.,1 was developed to eliminate cumbersome stereotactic procedures. We now describe a modified guide screw approach that is rapid and exceptionally safe; both of which are critical ethical considerations. Notably, our procedure now incorporates an infusion pump that allows up to 10 animals to be simultaneously injected with tumor cells. To demonstrate the utility of this procedure, we established human U87MG glioma cells as intracranial xenografts in mice, which were then treated with AMG102; a fully human antibody directed to HGF/scatter factor currently undergoing clinical evaluation2-5. Systemic injection of AMG102 significantly prolonged the survival of all mice with intracranial U87MG xenografts and resulted in a number of complete cures. This study demonstrates that the guide screw method is an inexpensive, highly reproducible approach for establishing intracranial xenografts. Furthermore, it provides a relevant physiological model for validating novel therapeutic strategies for the treatment of brain cancers. PMID:21968439

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

    PubMed

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

    2014-05-01

    The conflict between animal costs and human benefits has dominated public as well as academic debates about animal research. However, surveys of public perceptions of animal research rarely focus on this part of attitude formation. This paper traces the prevalence of different attitudes to animal research in the public when people are asked to take benefit and cost considerations into account concurrently. Results from the examination of two representative samples of the Danish public identify three reproducible attitude stances. Approximately 30-35% of people questioned approved of animal research quite strongly, and 15-20% opposed animal research. The remaining 50% were reserved in their views. Further studies will ideally use the measure developed here to make possible relatively fine-grained comparisons and understandings of differences between populations and changes in attitudes over time. PMID:23825251

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

    SciTech Connect

    Dasenbrock, Clemens . E-mail: clemens-dasebrock@bc.boehringer-ingelheim.com

    2005-09-01

    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.

  5. [Animal experimentation, animal welfare and scientific research].

    PubMed

    Tal, H

    2013-10-01

    Hundreds of thousands of laboratory animals are being used every year for scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs, and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In addition to the animals sacrificed to promote scientific research, millions of animals slain every year for other purposes such as meat and fine leather fashion industries. While opening a front against all is an impossible and perhaps an unjustified task, the state of Israel enacted the Animal Welfare (Animal Experimentation) Law (1994). The law aims to regulate scientific animal experiments and to find the appropriate balance between the need to continue to perform animal experiments for the advancement of research and medicine, and at the same time to avoid unnecessary trials and minimize animal suffering. Among other issues the law deals with the phylogenetic scale according to which experimental animals should be selected, experiments for teaching and practicing, and experiments for the cosmetic industry. This article discusses bioethics considerations in animal experiments as well as the criticism on the scientific validity of such experiments. It further deals with the vitality of animal studies and the moral and legal obligation to prevent suffering from laboratory animals. PMID:24660572

  6. Toxicology and carcinogenesis studies of p,p'-dichlorodiphenyl sulfone in rats and mice.

    PubMed

    Chhabra, R S; Herbert, R A; Bucher, J R; Travlos, G S; Johnson, J D; Hejtmancik, M R

    2001-03-01

    p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the production of polysulfones and polyethersufones, a family of thermoplastics. DDS was studied because of its high production volume and use. In toxicology studies, 10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30, 100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end of the studies. Mean body weights of groups exposed to 300 ppm or greater were significantly decreased. Liver and kidney in rats and liver in mice were the major target organs of DDS toxicity. Dose-related increases in liver weights and incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed groups. Nephropathy was seen in male and female rats only at and above 300 ppm. Neurotoxicity evaluations were negative in DDS-treated animals. Clinical chemistry and hematology parameters were minimally affected. In the 2-year toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks. Survival of exposed groups was not affected. There were no clinical signs of toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS-treated groups. Liver was the only target organ of DDS-induced toxicity. The incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the incidence of bile duct hyperplasia and centrilobular degeneration in female rats was significantly greater than in controls. A no-observed-adverse-effect level (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for rats. DDS was not carcinogenic in these studies. PMID:11222870

  7. Conjugated linoleic acid and atherosclerosis: studies in animal models.

    PubMed

    Mitchell, Patricia L; McLeod, Roger S

    2008-08-01

    Conjugated linoleic acids (CLA) are isomeric forms of linoleic acid (LA) containing two conjugated sites of unsaturation. The most abundant dietary form of CLA is the cis-9,trans-11 (c-9,t-11) isomer that is found in the fatty tissues and milk of ruminant animals. CLA can also be acquired by ingestion of supplements, which are usually equimolar mixtures of the c-9,t-11 and t-10,c-12 CLA. For more than a decade, the potential for CLA to modify atherosclerosis in animal models has been examined. However, to date, the studies have failed to reach consensus on whether CLA can be effective in reducing the incidence or severity of atherosclerotic lesions, or whether or not plasma lipid and lipoprotein levels can be improved with CLA supplementation. This review will examine the evidence for and against a role for CLA in atherosclerosis, with a focus on the rabbit, the hamster, and the apoE-deficient mouse. PMID:18756324

  8. Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal Study

    PubMed Central

    Ryu, Kyeung A.; Lyu, Ah-Ra; Park, Heesung; Choi, Jin Woong; Hur, Gang Min; Park, Yong-Ho

    2015-01-01

    The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model. PMID:26308864

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

    PubMed

    Soellner, Liane; Olejniczak, Klaus

    2013-02-01

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

  10. Genetically modified animal models as tools for studying bone and mineral metabolism.

    PubMed

    Davey, Rachel A; MacLean, Helen E; McManus, Julie F; Findlay, David M; Zajac, Jeffrey D

    2004-06-01

    Genetic modification of mice is a powerful tool for the study of bone development and metabolism. This review discusses the advantages and disadvantages of various approaches used in bone-related research and the contributions these studies have made to bone biology. Genetic modification of mice is a powerful tool for the study of bone development and metabolism. This review discusses the advantages and disadvantages of various approaches used in bone-related research and the contributions these studies have made to bone biology. The approaches to genetic modification included in this review are (1) overexpression of genes, (2) global gene knockouts, (3) tissue-specific gene deletion, and (4) gene knock-in models. This review also highlights issues that should be considered when using genetically modified animal models, including the rigorous control of genetic background, use of appropriate control lines, and confirmation of tissue specificity of gene expression where appropriate. This technology provides a unique and powerful way to probe the function of genes and is already revolutionizing our approach to understanding the physiology of bone development and metabolism. PMID:15125787

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

    Griep, A.E.; Lambert, P.F.

    1994-05-01

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

  13. Using Computational and Mechanical Models to Study Animal Locomotion

    PubMed Central

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

    2012-01-01

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

  14. Methyl isocyanate: reproductive and development toxicology studies in Swiss mice

    SciTech Connect

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

    1987-06-01

    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.

  15. Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice.

    PubMed Central

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

    1987-01-01

    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. PMID:3622429

  16. Molecular study of worldwide distribution and diversity of soil animals

    PubMed Central

    Wu, Tiehang; Ayres, Edward; Bardgett, Richard D.; Wall, Diana H.; Garey, James R.

    2011-01-01

    The global distribution of soil animals and the relationship of below-ground biodiversity to above-ground biodiversity are not well understood. We examined 17,516 environmental 18S rRNA gene sequences representing 20 phyla of soil animals sampled from 11 locations covering a range of biomes and latitudes around the world. No globally cosmopolitan taxa were found and only 14 of 2,259 operational taxonomic units (OTUs) found were common to four or more locations. Half of those were circumpolar and may reflect higher connectivity among circumpolar locations compared with other locations in the study. Even when OTU assembly criteria were relaxed to approximate the family taxonomic level, only 34 OTUs were common to four or more locations. A comparison of our diversity and community structure data to environmental factors suggests that below-ground animal diversity may be inversely related to above-ground biodiversity. Our data suggest that greater soil inorganic N and lower pH could explain the low below-ground biodiversity found at locations of high above-ground biodiversity. Our locations could also be characterized as being dominated by microarthropods or dominated by nematodes. Locations dominated by arthropods were primarily forests with lower soil pH, root biomass, mean annual temperature, low soil inorganic N and higher C:N, litter and moisture compared with nematode-dominated locations, which were mostly grasslands. Overall, our data indicate that small soil animals have distinct biogeographical distributions and provide unique evidence of the link between above-ground and below-ground biodiversity at a global scale. PMID:22006309

  17. Molecular study of worldwide distribution and diversity of soil animals.

    PubMed

    Wu, Tiehang; Ayres, Edward; Bardgett, Richard D; Wall, Diana H; Garey, James R

    2011-10-25

    The global distribution of soil animals and the relationship of below-ground biodiversity to above-ground biodiversity are not well understood. We examined 17,516 environmental 18S rRNA gene sequences representing 20 phyla of soil animals sampled from 11 locations covering a range of biomes and latitudes around the world. No globally cosmopolitan taxa were found and only 14 of 2,259 operational taxonomic units (OTUs) found were common to four or more locations. Half of those were circumpolar and may reflect higher connectivity among circumpolar locations compared with other locations in the study. Even when OTU assembly criteria were relaxed to approximate the family taxonomic level, only 34 OTUs were common to four or more locations. A comparison of our diversity and community structure data to environmental factors suggests that below-ground animal diversity may be inversely related to above-ground biodiversity. Our data suggest that greater soil inorganic N and lower pH could explain the low below-ground biodiversity found at locations of high above-ground biodiversity. Our locations could also be characterized as being dominated by microarthropods or dominated by nematodes. Locations dominated by arthropods were primarily forests with lower soil pH, root biomass, mean annual temperature, low soil inorganic N and higher C:N, litter and moisture compared with nematode-dominated locations, which were mostly grasslands. Overall, our data indicate that small soil animals have distinct biogeographical distributions and provide unique evidence of the link between above-ground and below-ground biodiversity at a global scale. PMID:22006309

  18. Weaknesses and Pitfalls of Using Mice and Rats in Cancer Chemoprevention Studies

    PubMed Central

    Ma, Yukui; Jia, Yuping; Chen, Lichan; Ezeogu, Lewis; Yu, Baofa; Xu, Ningzhi; Liao, D. Joshua

    2015-01-01

    Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals with a much longer lifespan should be used to bridge the lifespan gap between the rodents and humans. There are many transgenic mouse models of carcinogenesis available, in which DNA promoters are used to activate transgenes. One promoter may activate the transgene in multiple cell types while different promoters are activated at different ages of the mice. These spatial and temporal aspects of transgenes are often neglected and may be pitfalls or weaknesses in chemoprevention studies. The variation in the copy number of the transgene may widen data variation and requires use of more animals. Models of chemically-induced carcinogenesis do not have these transgene-related defects, but chemical carcinogens usually damage metabolic organs or tissues, thus affecting the metabolism of the chemopreventive agents. Moreover, many genetically edited and some chemically-induced carcinogenesis models produce tumors that exhibit cancerous histology but are not cancers because the tumor cells are still mortal, inducer-dependent, and unable to metastasize, and thus should be used with caution in chemoprevention studies. Lastly, since mice prefer an ambient temperature of 30-32°C, it should be debated whether future mouse studies should be performed at this temperature, but not at 21-23°C that cold-stresses the animals. PMID:26366220

  19. Weaknesses and Pitfalls of Using Mice and Rats in Cancer Chemoprevention Studies.

    PubMed

    Ma, Yukui; Jia, Yuping; Chen, Lichan; Ezeogu, Lewis; Yu, Baofa; Xu, Ningzhi; Liao, D Joshua

    2015-01-01

    Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals with a much longer lifespan should be used to bridge the lifespan gap between the rodents and humans. There are many transgenic mouse models of carcinogenesis available, in which DNA promoters are used to activate transgenes. One promoter may activate the transgene in multiple cell types while different promoters are activated at different ages of the mice. These spatial and temporal aspects of transgenes are often neglected and may be pitfalls or weaknesses in chemoprevention studies. The variation in the copy number of the transgene may widen data variation and requires use of more animals. Models of chemically-induced carcinogenesis do not have these transgene-related defects, but chemical carcinogens usually damage metabolic organs or tissues, thus affecting the metabolism of the chemopreventive agents. Moreover, many genetically edited and some chemically-induced carcinogenesis models produce tumors that exhibit cancerous histology but are not cancers because the tumor cells are still mortal, inducer-dependent, and unable to metastasize, and thus should be used with caution in chemoprevention studies. Lastly, since mice prefer an ambient temperature of 30-32°C, it should be debated whether future mouse studies should be performed at this temperature, but not at 21-23°C that cold-stresses the animals. PMID:26366220

  20. Endosomal abnormalities related to amyloid precursor protein in cholesterol treated cerebral cortex neuronal cells derived from trisomy 16 mice, an animal model of Down syndrome.

    PubMed

    Arriagada, Christian; Astorga, César; Atwater, Illani; Rojas, Eduardo; Mears, David; Caviedes, Raúl; Caviedes, Pablo

    2007-08-16

    The CNh and CTb cell lines are derived from the cerebral cortex of normal and trisomy 16 mice, an animal model of human trisomy 21, Down syndrome (DS), and represent in vitro models to study cellular events associated with the human condition. Amyloid precursor protein (APP) plays an important role in the development of neuropathology associated with DS and cholesterol in the amyloidogenic processing of APP. There is also increasing evidence of alterations in the recycling pathway of the early endosome compartment in nervous tissue from DS. In the present study, we report endosomal abnormalities related to amyloid precursor protein in cholesterol-treated CTb cells. Colocalization studies revealed the presence of APP-derived products in early endosomal compartments in both cell lines. Using internalization and immunoprecipitation techniques, differential effects were observed between the normal and trisomic cell lines when treated with cholesterol. Internalization experiments showed that the CTb cell line accumulates internalized APP in intracellular compartments for longer periods of time when compared to the CNh cell line. Immunoprecipitation revealed a differential interaction between the trafficking-related protein Rab4 and APP in the neuronal cell lines CNh and CTb. The present study suggests a putative mechanism by which overexpressed APP accumulates in intracellular compartments related to the endosomal trafficking pathway in individuals with DS, and highlights the usefulness of the CTb cell line as a model to study altered APP metabolism related to this genetic condition. PMID:17706358

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

    PubMed Central

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

    2014-01-01

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

  2. How Can We Study the Evolution of Animal Minds?

    PubMed Central

    Cauchoix, Maxime; Chaine, Alexis S.

    2016-01-01

    During the last 50 years, comparative cognition and neurosciences have improved our understanding of animal minds while evolutionary ecology has revealed how selection acts on traits through evolutionary time. We describe how cognition can be subject to natural selection like any other biological trait and how this evolutionary approach can be used to understand the evolution of animal cognition. We recount how comparative and fitness methods have been used to understand the evolution of cognition and outline how these approaches could extend our understanding of cognition. The fitness approach, in particular, offers unprecedented opportunities to study the evolutionary mechanisms responsible for variation in cognition within species and could allow us to investigate both proximate (i.e., neural and developmental) and ultimate (i.e., ecological and evolutionary) underpinnings of animal cognition together. We highlight recent studies that have successfully shown that cognitive traits can be under selection, in particular by linking individual variation in cognition to fitness. To bridge the gap between cognitive variation and fitness consequences and to better understand why and how selection can occur on cognition, we end this review by proposing a more integrative approach to study contemporary selection on cognitive traits combining socio-ecological data, minimally invasive neuroscience methods and measurement of ecologically relevant behaviors linked to fitness. Our overall goal in this review is to build a bridge between cognitive neuroscientists and evolutionary biologists, illustrate how their research could be complementary, and encourage evolutionary ecologists to include explicit attention to cognitive processes in their studies of behavior. PMID:27014163

  3. Using animal models to study post-partum psychiatric disorders

    PubMed Central

    Perani, C V; Slattery, D A

    2014-01-01

    The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24527704

  4. Experimental Shigella Infections in Laboratory Animals I. Antagonism by Human Normal Flora Components in Gnotobiotic Mice 12

    PubMed Central

    Maier, Bruce R.; Hentges, David J.

    1972-01-01

    Germfree mice were associated with selected species of human intestinal bacteria and then challenged with a streptomycin-resistant Shigella flexneri strain. Antagonism against Shigella was most pronounced in mice associated with Escherichia coli and least pronounced in mice associated with Bacteroides fragilis. A moderate degree of antagonism could be demonstrated in mice associated with either Streptococcus faecalis or Bifidobacterium adolescentis. Shigella persisted in the cecal contents of E. coli-associated mice at very low, stable levels. Shigella populations were reduced to levels below detection in the ceca of mice diassociated with E. coli and Bacteroides. Upon subsequent administration of streptomycin, Bacteroides disappeared from the ceca. The E. coli population was greatly reduced, and Shigella reappeared at very high population levels as an apparent recombinant which resembled E. coli biochemically. A streptomycin-resistant E. coli population subsequently emerged and became dominant in the ceca. Shigella concomitantly declined to levels below detection. PMID:4631914

  5. Experimental study on light induced influence model to mice using support vector machine

    NASA Astrophysics Data System (ADS)

    Ji, Lei; Zhao, Zhimin; Yu, Yinshan; Zhu, Xingyue

    2014-08-01

    Previous researchers have made studies on different influences created by light irradiation to animals, including retinal damage, changes of inner index and so on. However, the model of light induced damage to animals using physiological indicators as features in machine learning method is never founded. This study was designed to evaluate the changes in micro vascular diameter, the serum absorption spectrum and the blood flow influenced by light irradiation of different wavelengths, powers and exposure time with support vector machine (SVM). The micro images of the mice auricle were recorded and the vessel diameters were calculated by computer program. The serum absorption spectrums were analyzed. The result shows that training sample rate 20% and 50% have almost the same correct recognition rate. Better performance and accuracy was achieved by third-order polynomial kernel SVM quadratic optimization method and it worked suitably for predicting the light induced damage to organisms.

  6. Critical appraisal of the duration of chronic animal toxicity studies

    SciTech Connect

    Lumley, C.E.; Walker, S.R.

    1986-03-01

    One method of assessing the contribution of studies of longer than 6 months to a safety evaluation program is to compare retrospectively the findings in toxicity tests carried out for 6 months or less with those observed after 6 months. The Center for Medicines Research has therefore established a databank comprising animal toxicological data obtained from pharmaceutical companies in Europe. Twenty-one companies have provided data for 124 compounds (214 studies), including 88 studies of 65 compounds where comparable short-term (less than or equal to 6 months) and long-term (greater than 6 months) data are available. The results from the 88 studies show that, excluding the possibility of identifying carcinogens, tests of longer than 6 months have not added to the overall safety evaluation of these compounds.

  7. Selected 68Ga-siderophores versus 68Ga-colloid and 68Ga-citrate: biodistribution and small animal imaging in mice

    PubMed Central

    Petrik, Milos; Vlckova, Adela; Novy, Zbynek; Urbanek, Lubor; Haas, Hubertus; Decristoforo, Clemens

    2016-01-01

    Background 68Ga-triacetylfusarinine C (TAFC) and 68Ga-ferrioxamine E (FOXE) show great potential to be used as highly sensitive and selective tracers for Aspergillus infection imaging. Here we report on a comparison of the ex vivo biodistribution and small animal imaging of 68Ga-TAFC and 68Ga-FOXE versus 68Ga-colloid and 68Ga-citrate as unspecific control in mice. Methods The radiochemical purity of tested 68Ga labelled tracers was determined by RP-HPLC or ITLC-SG. Ex vivo biodistribution was studied in normal DBA/2 mice 30 min and 90 min p.i. Static and dynamic imaging were performed using µPET/CT. Results 68Ga-TAFC and 68Ga-FOXE showed rapid renal excretion and low blood values even 90 min p.i. 68Ga-TAFC showed almost no retention in other organs while 68Ga-FOXE displayed some uptake in gastrointestinal tract. 68Ga-colloid and 68Ga-citrate revealed significantly different ex vivo biodistribution. 68Ga-colloid showed pronounced radioactivity retention in the liver, while 68Ga-citrate displayed high blood values and significant retention of radioactivity in highly perfused organs. Conclusions From the results, both 68Ga-TAFC and 68Ga-FOXE have excellent and significantly different in vivo behaviour compared to 68Ga-colloid and 68Ga-citrate. 68Ga-TAFC in particular confirmed its great potential use as a specific tracer for Aspergillus infection imaging. PMID:25363728

  8. Using Dried Blood Spot Sampling to Improve Data Quality and Reduce Animal Use in Mouse Pharmacokinetic Studies

    PubMed Central

    Wickremsinhe, Enaksha R; Perkins, Everett J

    2015-01-01

    Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 µL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal—often to a single collection per mouse—thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 µL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study. PMID:25836959

  9. Advances in genome studies in plants and animals.

    PubMed

    Appels, R; Nystrom-Persson, J; Keeble-Gagnere, G

    2014-03-01

    The area of plant and animal genomics covers the entire suite of issues in biology because it aims to determine the structure and function of genetic material. Although specific issues define research advances at an organism level, it is evident that many of the fundamental features of genome structure and the translation of encoded information to function share common ground. The Plant and Animal Genome (PAG) conference held in San Diego (California), in January each year provides an overview across all organisms at the genome level, and often it is evident that investments in the human area provide leadership, applications, and discoveries for researchers studying other organisms. This mini-review utilizes the plenary lectures as a basis for summarizing the trends in the genome-level studies of organisms, and the lectures include presentations by Ewan Birney (EBI, UK), Eric Green (NIH, USA), John Butler (NIST, USA), Elaine Mardis (Washington, USA), Caroline Dean (John Innes Centre, UK), Trudy Mackay (NC State University, USA), Sue Wessler (UC Riverside, USA), and Patrick Wincker (Genoscope, France). The work reviewed is based on published papers. Where unpublished information is cited, permission to include the information in this manuscript was obtained from the presenters. PMID:24626952

  10. A Gamma Ray Imaging Device for Small-Animal Studies

    NASA Astrophysics Data System (ADS)

    Saunders, Robert; Bradley, Eric; Majewski, Stan; Saha, Margaret S.; Weisenberger, Andrew G.; Welsh, Robert E.

    1999-11-01

    A novel, modular nuclear imaging device for in vivo imaging of small animals is described. A segmented scintillator is coupled to a position-sensitive photomultiplier. This combination is used to view the living system under study with a variety of collimators employed to limit the angular acceptance. A personal computer is coupled to a CAMAC electronic system for event-by-event data acquisition and subsequent selective data analysis. The system has been designed to exploit the availability of a wide range of ligands tagged with the isotope 125I. It has most recently been employed for a study of the transport of the cocaine analog, RTI-55, to the brain of a mouse. Results of studies to date and options for future expansion of the system will be described.

  11. Effects of Developmental Bisphenol A Exposure on Reproductive-Related Behaviors in California Mice (Peromyscus californicus): A Monogamous Animal Model

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

    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

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

  13. Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice.

    PubMed

    Burleigh-Flayer, H; Garman, R; Neptun, D; Bevan, C; Gardiner, T; Kapp, R; Tyler, T; Wright, G

    1997-04-01

    The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm. PMID:9143479

  14. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    SciTech Connect

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

    1990-12-01

    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.

  15. Dominant lethal study of alpha-asarone in male mice.

    PubMed

    Chamorro, G; Garduño, L; Martínez, E; Madrigal, E; Tamariz, J; Salazar, M

    1998-10-15

    Alpha-asarone is a hypolipidaemic agent obtained from Guatteria gaumeri, a medical plant used in Mexico to treat hypercholesteraemia and cholelithiasis. alpha-Asarone has been shown to be hepatocarcinogenic and mutagenic in a human lymphocyte assay, a murine bone marrow cell assay and in an unscheduled DNA synthesis assay. In this study, alpha-asarone was tested for dominant lethal effects in male CF1 mice. The drug was given orally at doses of 0, 10 and 30 mg/kg per day for 5 days. Males were mated weekly with eight consecutive batches of naive, nulliparous female mice. Repeated matings revealed no perceptible effect of alpha-asarone on the incidence of pregnancy. Examination of surgically exposed uteri and ovaries of pregnant females on day 13-15 of gestation revealed an increased incidence of post-implantation loss. Semen examination of a separate group of mice showed a decreased concentration and motility of spermatozoa. These results suggest a dominant lethal mutation as well as direct alpha-asarone toxicity to spermatozoa by in treated mice. PMID:9817077

  16. Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice.

    PubMed

    Sharma, Meena R; Werth, Benjamin; Werth, Victoria P

    2011-01-01

    Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Nonxenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH1 and Balb/c were exposed to UVB and then evaluated 3 or 20 h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of tumor necrosis factor-α (TNF-α) mRNA, accumulation of glycosaminoglycans, particularly hyaluronan in the epidermis and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNF-α mRNA or chondroitin sulfate. Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice and to a lesser extent in SKH1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging. PMID:21332482

  17. Lagochilascaris minor: Susceptibility and Resistance to Experimental Infection in Mice Is Independent of H-2a Haplotype and Correlates with the Immune Response in Immunized Animals

    PubMed Central

    Spadafora-Ferreira, Mônica; Fernandes, Luciana Caetano; Hoffman Pfrimer, Irmtraut Araci; Pichiteli, Cássia Regina; Vilarinho Tambourgi, Denise; de Souza Lino-Junior, Ruy; Carvalhaes, Mara Silvia

    2010-01-01

    Recently, we demonstrated that C57BL/6 mice are more susceptible to experimental lagochilascariosis than BALB/c mice. To investigate the pattern of infection and the role of the genetic background on susceptibility to infection, we studied experimental lagochilascariosis in H-2a identical B10.A and A/J mice. Infected B10.A mice had a lower survival ratio and more severe lesions in the lungs than did A/J mice. Splenocytes of A/J mice immunized with the crude extract of the parasite showed increased proliferation and produced a higher level of interleukin 10 and interferon-γ in the presence of CE or concanavalin A when compared to B10.A mice. This suggests that resistance of A/J mice may be due to less severe lesions in lungs and other organs and a better immune response to parasite antigens. This paper provides evidence that major histocompatibility complex haplotype does not influence the survival to experimental infection with L. minor. PMID:20721343

  18. A Sensitivity study for a MICE liquid hydrogen absorber

    SciTech Connect

    Errede, D.; Rakhno, I.; /Illinois U., Urbana /Fermilab

    2004-11-01

    The International Muon Ionization Cooling Experiment (MICE) is devoted to a study of a muon cooling channel capable of giving the desired performance for a Neutrino Factory. One of the goals is achieving an absolute accuracy of measurements of emittance reduction as high as {+-} 0.1%. The paper describes results of a Monte Carlo study on allowed density variations of liquid hydrogen corresponding to the desired accuracy of the measurements.

  19. Epidemiological Study of Animal Leptospirosis in New Caledonia

    PubMed Central

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

    2013-01-01

    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. PMID:23533965

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

    PubMed

    Ozkanlar, Seckin; Akcay, Fatih

    2012-01-01

    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

  1. Linking etiologies in humans and animal models: studies of autism.

    PubMed

    Rodier, P M; Ingram, J L; Tisdale, B; Croog, V J

    1997-01-01

    Thalidomide has been shown to lead to a high rate of autism when exposure occurs during the 20th to 24th d of gestation. Both the critical period and the neurological deficits of the autistic cases indicate that they have sustained injuries to the cranial nerve motor nuclei. To determine whether such lesions characterize other cases of autism, the brain stem of an autistic case was compared to that of a control. The autopsy case showed abnormalities predicted by the thalidomide cases and evidence of shortening of the brain stem, a defect that could have occurred only during neural tube closure. To test whether animals can be similarly injured but remain viable, rats were treated with 350 mg/kg of valproic acid on day 11.5, 12, or 12.5 of gestation. Neuron counts showed reductions of cell numbers in the cranial nerve motor nuclei. Rats with motor neuron deficits also had cerebellar anomalies like those reported in studies of autistic cases, supporting the idea that these animals may be a useful model of the developmental injury that initiates autism. PMID:9100317

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    1982-04-07

    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)

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

    PubMed

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

    2013-08-01

    Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-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 β-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid β-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 β-glucosidase and the common mutations underlying Gaucher disease. PMID:23642305

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

    PubMed

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

    2008-07-01

    The ethics of animal-based research is a continuing area of debate, but ethical research protocols do not prevent scientific progress. In this paper, we argue that our current knowledge of the factors that affect reproductive processes provides researchers with a solid foundation upon which they can conduct more ethical research and simultaneously produce data of higher quality. We support this argument by showing how a deep understanding of the genetics, nutrition and temperament of our experimental animals can improve compliance with two of the '3 Rs', reduction and refinement, simply by offering better control over the variance in our experimental model. The outcome is a better experimental design, on both ethical and scientific grounds. PMID:18638100

  6. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

    PubMed

    Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

    2015-12-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia. PMID:26453015

  7. Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo

    PubMed Central

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K.

    2016-01-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  8. Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo.

    PubMed

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K

    2016-02-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  9. Copper metabolism in mottled mouse (Mus musculus) mutants. Studies of blotchy (Moblo) mice and a comparison with brindled (Mobr) mice.

    PubMed Central

    Mann, J R; Camakaris, J; Francis, N; Danks, D M

    1981-01-01

    1. Copper concentrations were low in many organs of Moblo/Y mice, but very high in the gut. Absorption of 64Cu was seen to be very low when related to the absorption of cyano[57Co]cobalamin. The results in Moblo/+ mice were intermediate. 2. Copper therapy temporarily ameliorated many effects of the mutation in Moblo/Y mice, but did not improve the rate of weight gain as has been achieved previously in Mobr/Y mice. Lower capacity for a 'depot dose' effect at the site of injection may explain the difference. 3. The distribution of 64Cu after administration into the bloodstream of Moblo/Y mice altered from an initially normal state to one that resembled the abnormal distribution of pre-existing copper by 48 h. This indicated that the later mechanisms of copper distribution were at fault. Moblo/+ mice were equally affected. 4. The alteration of copper homoeostasis in blotchy mice was similar to that observed in brindled mice previously and in the present studies, although generally less severe. This is consistent with allelism of the two mutations. PMID:7197928

  10. Carcinogenesis Studies of Cresols in Rats and Mice

    PubMed Central

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

    2010-01-01

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

  11. Development of an Animal Holding Facility for Space Shuttle studies

    NASA Technical Reports Server (NTRS)

    Berry, W. E.; Bowman, G. H.; Jagow, R. B.; Olcott, T. M.

    1981-01-01

    The modular Research Animal Holding Facility (RAHF) developed by NASA is described. Besides providing general housing for various animal species, the RAHF is designed to minimize disturbance of the specimens caused by vehicle and mission operations. The RAHF system offers life-sustaining capabilities, such as food, water, and waste removal, as well as environmental control. Modularity of construction to accommodate a variety of small animals and associated instrumentation ensures continued use of RAHF as the sophistication of experiments increases on subsequent missions.

  12. Swiss bare mice: a suitable model for transcutaneous in vivo Raman spectroscopic studies of breast cancer.

    PubMed

    Bhattacharjee, T; Kumar, Piyush; Maru, G; Ingle, A; Krishna, C Murali

    2014-01-01

    Breast cancer is the most common cancer affecting females worldwide. As early detection results in better prognosis, screening tools for breast cancer are being explored. Raman spectroscopy, a rapid, objective, and noninvasive tool, has shown promising results in the diagnosis of several cancers including breast cancer. For development as a screening tool, a study of spectral signatures associated with breast cancer progression is imperative. However, such studies are not possible in human subjects. Hence, there is a need for a suitable animal model, which is conducive to transcutaneous in vivo Raman spectroscopic measurements of breast with minimal interference from skin and hair and has contribution from functional mammary epithelium of breast. In this study, rodent models like C57, Swiss albino, Swiss bare, agouti mice, and Sprague-Dawley rats were evaluated. Among these models, transcutaneous breast spectra of hairless Swiss bare mice have the best signal-to-noise ratio and were closest to reported ex vivo as well as intraoperative in vivo human breast spectra. Principal component-linear discriminant analysis of several anatomical sites confirms minimal skin interference and suggests contribution from functional mammary epithelium of breast. Moreover, transcutaneous spectra from normal breast and breast tumors of Swiss bare mice could be classified with 99% efficiency, which is better than the previous reports. Thus, Swiss bare mice model may be better suited for transcutaneous in vivo Raman spectroscopic studies of breast physiology and pathology, especially breast cancer. Prospectively, in addition to cancer progression, breast-to-bone metastasis can also be studied, since these anatomical sites can be uniquely classified. PMID:23708992

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons and causes progressive muscle weakness and atrophy. The etiology and pathogenesis of ALS are largely unknown and no effective treatment is presently available. About 10% of patients have the familial or inherited form of the disease (fALS), among which 20% is linked to mutations with Cu2+/Zn2+ superoxide dismutase (mSOD1). Transgenic animals expressing human mSOD1 are excellent models for understanding not only fALS but sporadic ALS as well. Pathological features in both ALS patients and mSOD1 transgenic animals’ spinal cords share commonalties including the accumulation of misfolded protein inclusions. Recent proteomic investigations on ALS animal models have discovered alterations in protein expression, protein-protein interactions and post-translational modifications. These efforts have revealed aspects of potential pathogenic mechanisms and identified probable therapeutic targets. The present review summarizes the major findings of proteomics studies performed on the mSOD1 mice with particular emphasis on the spinal cord proteome. These results are compared with those reported using cell cultures or specimens obtained from ALS patients. The convergence of pathogenic processes on protein chaperone function, and its relationship to protein degradation, metabolic dysfunction and oxidative signaling events is discussed. PMID:19578526

  15. Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases.

    PubMed

    Koboziev, Iurii; Jones-Hall, Yava; Valentine, John F; Webb, Cynthia Reinoso; Furr, Kathryn L; Grisham, Matthew B

    2015-07-01

    Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases and assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient's bedside, it is becoming increasingly apparent that the mouse immune system is substantially different from the human. Indeed, it is well known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation, and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system to address important human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hematolymphoid cells in mice would provide investigators with a relatively inexpensive small animal model to study clinically relevant mechanisms and facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss the use of these unique mouse models to define the human-specific immunopathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation. PMID:26035036

  16. Animal Rights: Selected Resources and Suggestions for Further Study.

    ERIC Educational Resources Information Center

    Davidoff, Donald J.

    1989-01-01

    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.…

  17. Animal Rights: Selected Resources and Suggestions for Further Study.

    ERIC Educational Resources Information Center

    Davidoff, Donald J.

    1989-01-01

    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.

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

    SciTech Connect

    Lee, Don Haeng; Kang, Sung-Gwon Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-10-15

    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.

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

    PubMed Central

    Lynch, Emma; Angeloni, Lisa; Fristrup, Kurt; Joyce, Damon; Wittemyer, George

    2013-01-01

    Audio recordings made from free-ranging animals can be used to investigate aspects of physiology, behavior, and ecology through acoustic signal processing. On-animal acoustical monitoring applications allow continuous remote data collection, and can serve to address questions across temporal and spatial scales. We report on the design of an inexpensive collar-mounted recording device and present data on the activity budget of wild mule deer (Odocoileus hemionus) derived from these devices applied for a 2-week period. Over 3300 h of acoustical recordings were collected from 10 deer on their winter range in a natural gas extraction field in northwestern Colorado. Analysis of a subset of the data indicated deer spent approximately 33.5% of their time browsing, 20.8% of their time processing food through mastication, and nearly 38.3% of their time digesting through rumination, with marked differences in diel patterning of these activities. Systematic auditory vigilance was a salient activity when masticating, and these data offer options for quantifying wildlife responses to varying listening conditions and predation risk. These results (validated using direct observation) demonstrate that acoustical monitoring is a viable and accurate method for characterizing individual time budgets and behaviors of ungulates, and may provide new insight into the ways external forces affect wildlife behavior. PMID:23919149

  20. A feasibility study for the analysis of reparative dentinogenesis in pOBCol3.6GFPtpz transgenic mice

    PubMed Central

    Frozoni, M.; Balic, A.; Sagomonyants, K.; Zaia, A. A.; Line, S. R. P.; Mina, M.

    2012-01-01

    Aim To examine the feasibility of using the pOBCol3.6GFPtpz (3.6-GFP) transgenic mice as an in vivo model for studying the biological sequence of events during pulp healing and reparative dentinogenesis. Methodology Pulp exposures were created in the first maxillary molar of 12-16 week old 3.6-GFP transgenic mice with CD1 and C57/Bl6 genetic background. Direct pulp capping on exposed teeth were performed using mineral trioxide aggregate (MTA) followed by restoration with a light-cured adhesive system (AS) and composite resin. In control teeth, the AS was placed in direct contact with the pulp. Animals were euthanized at various time points after pulp exposure and capping. The maxillary arch was isolated, fixed and processed for histological and epifluorescence analysis to examine reparative dentinogenesis. Results Analysis of teeth immediately after pulp exposure revealed absence of odontoblasts expressing 3.6-GFP at the injury site. Evidence of reparative dentinogenesis was apparent at 4 weeks in 3.6-GFP mice in CD1 background and at 8 weeks in 3.6-GFP mice with C57/Bl6 background. The reparative dentine with both groups contained newly formed atubular-mineralized tissue resembling a dentine bridge and/or osteodentine that was lined by cells expressing 3.6-GFP as well as 3.6-GFP expressing cells embedded within the atubular matrix. Conclusion This study was conducted in a few animals and did not allow statistical analysis. The results revealed that the 3.6-GFP transgenic animals provide a unique model for direct analysis of cellular and molecular mechanisms of pulp repair and tertiary dentinogenesis in vivo. The study also shows the effects of the capping material and the genetic background of the mice in the sequence and timing of reparative dentinogenesis. PMID:22551423

  1. A study of quantification of aortic compliance in mice using radial acquisition phase contrast MRI

    NASA Astrophysics Data System (ADS)

    Zhao, Xuandong

    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.

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

    MedlinePlus

    ... find Resveratrol helps protect against cardiovascular disease in animal study June 3, 2014 Resveratrol, a compound found ... translatable to humans. Multiple studies on resveratrol in animal models, however, have presented ample evidence to support ...

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

    SciTech Connect

    Congdon, C.C.

    1987-05-01

    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.

  4. Progress in gene targeting: using mutant mice to study renal function and disease.

    PubMed

    Kohan, Donald E

    2008-08-01

    Genetic engineering in mice has provided much information about gene function in renal health and disease. This knowledge has largely come from conventional transgenic approaches. Recently, methods have been developed to control the cell type, timing and reversibility of target gene expression. Advances in identifying promoters conferring renal cell-specific gene regulation in vivo have greatly facilitated interpretation of gene targeting studies. Site-specific recombinases have permitted cell-specific knockout of genes; Cre is the preeminent recombinase, but recent progress with other recombinases, include Flp and PhiC31, will likely increase the usefulness of this class of enzymes. Temporally regulated gene expression, particularly using doxycycline- and tamoxifen-inducible systems, holds great promise for avoiding developmental effects of gene mutations as well as facilitating comparison of the same animal's phenotype before and after gene modification. RNA interference is undergoing tremendous growth and has great potential for achieving gene knockdown quickly and reversibly. To date, however, the utility of these systems in modifying renal function in transgenic mice remains unproven. Finally, new gene targeting tools are in development that may substantially simplify generation of transgenic animals. This review discusses the state-of-the-art in gene targeting in the kidney, reviewing function, indications and limitations of the molecular biologic tools. PMID:18418351

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

    PubMed Central

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

    2010-01-01

    Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice. PMID:21829300

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

    PubMed Central

    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

    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. PMID:22607191

  7. Molecular Heterogeneities of Adipose Depots - Potential Effects on Adipose-Muscle Cross-Talk in Humans, Mice and Farm Animals

    PubMed Central

    Komolka, Katrin; Albrecht, Elke; Wimmers, Klaus; Michal, Jennifer J.; Maak, Steffen

    2014-01-01

    Adipose tissue is considered as a major endocrine organ that secretes numerous proteins called adipokines. The heterogeneous nature of adipose tissue in different parts of the body suggests respective heterogeneity of proteomes and secretomes. This review consolidates knowledge from recent studies targeting the diversity of different adipose depots affecting the pattern of secreted adipokines and discusses potential consequences for the cross-talk between adipose and skeletal muscle in humans, rodent models and farm animals. Special attention is paid to muscle-associated fat depots like inter- and intramuscular fat that become focus of attention in the context of the rather new notion of skeletal muscle as a major endocrine organ. Understanding the complexity of communication between adipocytes and skeletal muscle cells will allow developing strategies for improvement of human health and for sustainable production of high quality meat. PMID:25057322

  8. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    PubMed

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. PMID:26467890

  9. Imaging Primary Lung Cancers in Mice to Study Radiation Biology

    SciTech Connect

    Kirsch, David G.; Grimm, Jan; Guimaraes, Alexander R.; Wojtkiewicz, Gregory R.; Perez, Bradford A.; Santiago, Philip M.; Anthony, Nikolas K.; Forbes, Thomas; Doppke, Karen

    2010-03-15

    Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

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

    SciTech Connect

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

    1986-09-01

    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.

  11. Genetic and ecological studies of animals in Chernobyl and Fukushima.

    PubMed

    Mousseau, Timothy A; Møller, Anders P

    2014-01-01

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

  12. Developmental effects of SSRIs: lessons learned from animal studies.

    PubMed

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

    2007-10-01

    Selective serotonin reuptake inhibitors (SSRIs) are utilized in the treatment of depression in pregnant and lactating women. SSRIs may be passed to the fetus through the placenta and the neonate through breastfeeding, potentially exposing them to SSRIs during peri- and postnatal development. However, the long-term effects of this SSRI exposure are still largely unknown. The simplicity and genetic amenability of model organisms provides a critical experimental advantage compared to studies with humans. This review will assess the current research done in animals that sheds light on the role of serotonin during development and the possible effects of SSRIs. Experimental studies in rodents show that administration of SSRIs during a key developmental window creates changes in brain circuitry and maladaptive behaviors that persist into adulthood. Similar changes result from the inhibition of the serotonin transporter or monoamine oxidase, implicating these two regulators of serotonin signaling in developmental changes. Understanding the role of serotonin in brain development is critical to identifying the possible effects of SSRI exposure. PMID:17706396

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

    MedlinePlus

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

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

    PubMed Central

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

    2012-01-01

    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 α, β, and γ (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

  15. The biological response to titanium and titanium-aluminium-vanadium alloy particles. II. Long-term animal studies.

    PubMed

    Rae, T

    1986-01-01

    The long-term tissue reactions to particulate titanium and titanium-aluminium-vanadium alloy were investigated by the intra-articular injection of material into the knee joints of mice. The tissue response was studied over a period of 2 to 52 weeks. In general, both materials were well tolerated, there was no evidence of necrosis and only a slight thickening of the synovium occurred around particles. Multinucleated giant cells were only rarely seen and no palpable tumours formed in any animal at any site. PMID:3955157

  16. On Some Issues of Human-Animal Studies: An Introduction.

    PubMed

    Métraux, Alexandre

    2016-03-01

    Animals are "in" - since prehistoric times when humans (or their ancient ancestors) were hunting animals, and when they fabricated the Paleolithic dog as well as the Paleolithic cat. In less general terms, animals are "in" since they received names and were listed, observed, mummified, turned into totems, and, later on, dissected, tortured under laboratory conditions, trained as experimental subjects or "purified" as model organisms. And they are massively "in" again, but now from overtly legal and moral points of view, at least since the last two decades of the twentieth century. This is to say that modern members of the species Homo sapiens have always been connected to animals of the most various kinds - from the human flea (Pulex irritans) and the cat flea (Ctenocephalides felis) to marine mammals, such as dolphins and whales, from horses to parrots, from scallops to worms, and so on. PMID:26903370

  17. Animal welfare and use of silkworm as a model animal.

    PubMed

    Sekimizu, N; Paudel, A; Hamamoto, H

    2012-08-01

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

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

    PubMed

    Ishii, Hiroyuki; Masuda, Yuichi; Miyagishima, Syunsuke; Fumino, Shogo; Takanishi, Atsuo; Laschi, Cecilia; Mazzolai, Barbara; Mattoli, Virgilio; Dario, Paolo

    2009-01-01

    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 or social learning. However, some researchers mention that the experiments on social interactions using animals are poorly-reproducible. Therefore, we consider that reproducibility of these experiments can be improved by using a robotic agent that interacts with an animal subject. Thus, we developed a small quadruped robot WR-2 (Waseda Rat No. 2) that behaves like a real rat. Proportion and DOF arrangement of WR-2 are designed based on those of a mature rat. This robot has four 3-DOF legs, a 2-DOF waist and a 1-DOF neck. A microcontroller and a wireless communication module are implemented on it. A battery is also implemented. Thus, it can walk, rear by limbs and groom its body. PMID:19965275

  19. Assessment of aortic pulse wave velocity by ultrasound: a feasibility study in mice

    NASA Astrophysics Data System (ADS)

    Faita, Francesco; Di Lascio, Nicole; Stea, Francesco; Kusmic, Claudia; Sicari, Rosa

    2014-03-01

    Pulse wave velocity (PWV) is considered a surrogate marker of arterial stiffness and could be useful for characterizing cardiovascular disease progression even in mouse models. Aim of this study was to develop an image process algorithm for assessing arterial PWV in mice using ultrasound (US) images only and test it on the evaluation of age-associated differences in abdominal aorta PWV (aaPWV). US scans were obtained from six adult (7 months) and six old (19 months) wild type male mice (strain C57BL6) under gaseous anaesthesia. For each mouse, diameter and flow velocity instantaneous values were achieved from abdominal aorta B-mode and PW-Doppler images; all measurements were obtained using edge detection and contour tracking techniques. Single-beat mean diameter and velocity were calculated and time-aligned, providing the lnD-V loop. aaPWV values were obtained from the slope of the linear part of the loop (the early systolic phase), while relative distension (relD) measurements were calculated from the mean diameter signal. aaPWV values for young mice (3.5±0.52 m/s) were lower than those obtained for older ones (5.12±0.98 m/s) while relD measurements were higher in young (25%±7%) compared with older animals evaluations (15%±3%). All measurements were significantly different between the two groups (P<0.01 both). In conclusion, the proposed image processing technique well discriminate between age groups. Since it provides PWV assessment just from US images, it could represent a simply and useful system for vascular stiffness evaluation at any arterial site in the mouse, even in preclinical small animal models.

  20. Experimental CO2 laser myringotomy: a preliminary animal study

    NASA Astrophysics Data System (ADS)

    Valtonen, Hannu J.; Poe, Dennis S.; Perrault, Donald F., Jr.; Lombardo, Igino; Pankratov, Michail M.; Shapshay, Stanley M.

    1995-05-01

    Myringotomy--a procedure in which a perforation is made in the tympanic membrane (TM) is performed to gain access to the middle ear for diagnostic or therapeutic reasons. Some medical conditions, especially middle ear infections require an opening that remains patent for weeks or even months. A conventional myringotomy usually closes in a few days which is insufficient time for an underlying disease to resolve. There have been studies reporting modest closure delays of myringotomies done by CO2 laser from the beginning of 1980's and the procedure has not gained popularity in clinical practice. Many of the mechanisms affecting TM healing delays remain unknown. In an animal model we investigated the closure rates of TM perforations after different types of myringotomies. The animals formed three experimental groups: (1) both ears had a semicircular myringotomy produced either with a knife or with a CO2 laser; (2) both ears had a round laser myringotomy (1.2 mm in diameter) produced either in a single shot or by a series of small overlapping shots; (3) both ears had laser myringotomy either kidney shaped (1.2 X 2 mm) or round (1.2 mm in diameter) produced by a series of small shots. All myringotomies closed within 42 days without complications. The mean patency of knife myringotomies was significantly shorter (9.8 days) than that of similar laser myringotomies (19.5 days). The mode of laser delivery did not have an effect on the closure rate. Kidney shaped CO2 laser myringotomies stayed patent significantly longer (mean 25.8 days) than circular (mean 11.4 days). The patency of smaller semicircular laser myringotomies was significantly longer than that of larger circular. The results indicate that certain geometries as well as use of the CO2 laser delays the closure of myringotomy. When myringotomy is performed for therapeutic reasons not only the size but also the shape should be considered as a factor for extending its length of patency. In the future CO2 laser may become an instrument for creating reliable myringotomies of different shapes and sizes.

  1. Widefield multiphoton excited fluorescence microscopy for animal study in vivo

    NASA Astrophysics Data System (ADS)

    Cheng, L.-C.; Chang, C.-Y.; Lin, C.-H.; Su, Y.-D.; Huang, T.-Y.; Chen, S.-J.

    2010-08-01

    Unlike conventional multiphoton excited microscopy according to pixel-by-pixel point scanning, a widefield multiphoton excited microscopy based on spatiotemporal focusing has been developed to construct three-dimensional (3D) multiphoton fluorescence images only with the need of an axial scanning. By implementing a 4.0 W 10 kHz femtosecond laser amplifier with an instant strong peak power and a fast TE-cooled EMCCD camera with an ultra-sensitive fluorescence detection, the multiphoton excited fluorescence images with the excitation area over 100 μm x 100 μm can be achieved at a frame rate up to 80 Hz. A mechanical shutter is utilized to control the exposure time of 1 ms, i.e. average ten laser pulses reach the fluorescent specimen, and hence an uniform enough multiphoton excited fluorescence image can be attained with less photobleaching. The Brownian motion of microbeads and 3D neuron cells of a rat cerebellum have been observed with a lateral spatial resolution of 0.24 μm and an axial resolution of 2.5 μm. Therefore, the developed widefield multiphoton microscopy can provide fast and high-resolution multiphoton excited fluorescence images for animal study in vivo.

  2. Of Fighting Flies, Mice, and Men: Are Some of the Molecular and Neuronal Mechanisms of Aggression Universal in the Animal Kingdom?

    PubMed Central

    Dierick, Herman A.

    2015-01-01

    Aggressive behavior is widespread in the animal kingdom, but the degree of molecular conservation between distantly related species is still unclear. Recent reports suggest that at least some of the molecular mechanisms underlying this complex behavior in flies show remarkable similarities with such mechanisms in mice and even humans. Surprisingly, some aspects of neuronal control of aggression also show remarkable similarity between these distantly related species. We will review these recent findings, address the evolutionary implications, and discuss the potential impact for our understanding of human diseases characterized by excessive aggression. PMID:26312756

  3. Rh glycoproteins in epithelial cells: lessons from rat and mice studies.

    PubMed

    Chambrey, R; Goossens, D; Quentin, F; Eladari, D

    2006-01-01

    Rhesus glycoproteins are a recently discovered family of ammonium transporters and a new branch of the Mep/AMT proteins superfamily that was identified more than 15 years ago in lower organisms and plants. Despite many ex vivo studies showing evidences that Rh glycoproteins can accelerate transmembrane NH3 or NH4+ transfer, their role in normal and disease physiology remains unknown. This review focuses on some of the different studies carried out in animal models to gain insight into Rh glycoprotein function. Immunolocalization studies have added new evidence that this protein family is related to ammonium transport or metabolism in epithelial cells. However, the absence of distal tubular acidosis or hyperammonemia in Rhbg KO mice have raised new questions about the physiological significance of these proteins. PMID:16563831

  4. Molecular epidemiological studies on animal trypanosomiases in Ghana

    PubMed Central

    2012-01-01

    Background African trypanosomes are extracellular protozoan parasites that are transmitted between mammalian hosts by the bite of an infected tsetse fly. Human African Trypanosomiasis (HAT) or sleeping sickness is caused by Trypanosoma brucei rhodesiense or T. brucei gambiense, while African Animal Trypanosomiasis (AAT) is caused mainly by T. vivax, T. congolense, T. simiae,T. evansi and T. brucei brucei. Trypanosomiasis is of public health importance in humans and is also the major constraint for livestock productivity in sub-Saharan African countries. Scanty information exists about the trypanosomiasis status in Ghana especially regarding molecular epidemiology. Therefore, this study intended to apply molecular tools to identify and characterize trypanosomes in Ghana. Methods A total of 219 tsetse flies, 248 pigs and 146 cattle blood samples were collected from Adidome and Koforidua regions in Ghana in 2010. Initial PCR assays were conducted using the internal transcribed spacer one (ITS1) of ribosomal DNA (rDNA) primers, which can detect most of the pathogenic trypanosome species and T. vivax-specific cathepsin L-like gene primers. In addition, species- or subgroup-specific PCRs were performed for T. b. rhodesiense, T. b. gambiense, T. evansi and three subgroups of T. congolense. Results The overall prevalence of trypanosomes were 17.4% (38/219), 57.5% (84/146) and 28.6% (71/248) in tsetse flies, cattle and pigs, respectively. T. congolense subgroup-specific PCR revealed that T. congolense Savannah (52.6%) and T. congolense Forest (66.0%) were the endemic subgroups in Ghana with 18.6% being mixed infections. T. evansi was detected in a single tsetse fly. Human infective trypanosomes were not detected in the tested samples. Conclusion Our results showed that there is a high prevalence of parasites in both tsetse flies and livestock in the study areas in Ghana. This enhances the need to strengthen control policies and institute measures that help prevent the spread of the parasites. PMID:23025330

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

    PubMed

    Boukerche, S; Aouacheri, W; Saka, S

    2007-01-01

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

  6. Detection of ICAM-1 in experimentally induced colitis of ICAM-1-deficient and wild-type mice: an immunohistochemical study.

    PubMed

    Bendjelloul, F; Rossmann, P; Malý, P; Mandys, V; Jirkovská, M; Prokesová, L; Tucková, L; Tlaskalová-Hogenová, H

    2000-12-01

    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 control strain the immunohistochemical staining showed a very pronounced endothelial upregulation of ICAM-1 after the DSS treatment observed in areas of inflammatory infiltrate, especially in venules or arterioles of the propria and submucosa, and partly in the mesocolon. DSS-fed ICAM-1-deficient mice showed no endothelial enhancement and only faint staining of venules or capillaries approaching that encountered in the control ICAM-1-deficient animals. Our data indicate that ICAM-1 may play a crucial role in the development of acute intestinal inflammation, consistent with our finding that ICAM-1 deficiency can obviate severe forms of experimentally induced colitis in mice. PMID:11254085

  7. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-controlled animal studies when the results of those animal studies establish that the biological product is reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the... of the substance and its prevention or substantial reduction by the product; (2) The effect...

  8. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-controlled animal studies when the results of those animal studies establish that the biological product is reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the... of the substance and its prevention or substantial reduction by the product; (2) The effect...

  9. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... met based on adequate and well-controlled animal studies when the results of those animal studies... sufficiency of animal data, the agency may take into account other data, including human data, available to... pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by...

  10. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-controlled animal studies when the results of those animal studies establish that the biological product is reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the... of the substance and its prevention or substantial reduction by the product; (2) The effect...

  11. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... met based on adequate and well-controlled animal studies when the results of those animal studies... sufficiency of animal data, the agency may take into account other data, including human data, available to... pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by...

  12. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... met based on adequate and well-controlled animal studies when the results of those animal studies... sufficiency of animal data, the agency may take into account other data, including human data, available to... pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by...

  13. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... met based on adequate and well-controlled animal studies when the results of those animal studies... sufficiency of animal data, the agency may take into account other data, including human data, available to... pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by...

  14. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-controlled animal studies when the results of those animal studies establish that the biological product is reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the... of the substance and its prevention or substantial reduction by the product; (2) The effect...

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

    PubMed

    Takahashi-Omoe, H; Omoe, K

    2007-07-01

    We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan. PMID:17416418

  16. Role of endogenous prostacyclin in gastric ulcerogenic and healing responses--a study using IP-receptor knockout mice.

    PubMed

    Takeuchi, K; Kato, S; Ogawa, Y; Kanatsu, K; Umeda, M

    2001-01-01

    Endogenous prostaglandins (PGs) play an important role in the cytoprotective and healing responses in the stomach, by altering various functions, i.e., an increase of the mucosal blood flow, yet the role of prostacyclin (PGI(2)) and its receptor (IP-receptor) in these responses remains unclarified. In the present study, we used IP-receptor knockout mice [IP (-/-)] and examined the importance of IP-receptors in gastric ulcerogenic, cytoprotective and healing responses in these animals. The studies included the ulcerogenic response to cold-restraint stress, the cytoprotective response to a mild irritant (20 mM taurocholate: TC) and capsaicin, and the healing response of chronic gastric ulcers induced by thermo-cauterization. We first checked the absence of IP-receptors by examining the effect of cicaprost (a PGI(2) agonist, topical mucosal application) on gastric mucosal blood flow and found that this agent increased the mucosal blood flow in wild-type [WT (+/+)] mice but not in IP (+/-) mice. Cold-restraint stress (4 h) induced gastric lesions in both groups of mice, but the severity of damage was significantly greater in IP (-/-) mice. Prior p.o. administration of both TC and capsaicin exhibited a marked cytoprotection against HCl/ethanol-induced gastric damage in WT (+/+) mice, both responses being significantly mitigated in the presence of indomethacin. The adaptive cytoprotection induced by TC was similarly observed in IP (-/-) mice, while the capsaicin protection was totally attenuated in the animals lacking IP receptors. On the other hand, the healing of gastric ulcers was significantly delayed by daily administration of indomethacin in WT (+/+) mice. However, this process was not altered in IP (-/-) mice. These results suggest that endogenous PGI(2) is involved in the gastric ulcerogenic response to stress, but not in the healing of pre-existing gastric ulcers. In addition, PGI(2) and its receptors may play a crucial role in capsaicin-induced gastric protection but not in the adaptive cytoprotection-induced by mild irritants. PMID:11595421

  17. Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

    PubMed

    Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

    2016-06-01

    The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day-old trabecular bone in vertebrae (31%) and in 2-month old trabecular bone in both tibia (31%) and vertebrae (4%). There was also a 16% lower carbonate-to-phosphate ratio in vertebral trabeculae and a correspondingly higher (22%) carbonate-to-phosphate ratio in 2month-old vertebral cortices. At age 3-months-of-age, male femurs with both a Col1a2(+/G610C) allele and a Lrp5 high bone mass allele (Lrp5+/A214V) showed an improvement in bone composition, presenting higher trabecular carbonate-to-phosphate ratio (18%) and lower trabecular and cortical acid-phosphate substitutions (8% and 18%, respectively). Together, these results indicate that mutant collagen α2(I) chain affects both bone quantity and composition, and the usefulness of this model for studies of potential OI therapies such as anti-sclerostin treatments. PMID:27083399

  18. Automated interactive video playback for studies of animal communication.

    PubMed

    Butkowski, Trisha; Yan, Wei; Gray, Aaron M; Cui, Rongfeng; Verzijden, Machteld N; Rosenthal, Gil G

    2011-01-01

    Video playback is a widely-used technique for the controlled manipulation and presentation of visual signals in animal communication. In particular, parameter-based computer animation offers the opportunity to independently manipulate any number of behavioral, morphological, or spectral characteristics in the context of realistic, moving images of animals on screen. A major limitation of conventional playback, however, is that the visual stimulus lacks the ability to interact with the live animal. Borrowing from video-game technology, we have created an automated, interactive system for video playback that controls animations in response to real-time signals from a video tracking system. We demonstrated this method by conducting mate-choice trials on female swordtail fish, Xiphophorus birchmanni. Females were given a simultaneous choice between a courting male conspecific and a courting male heterospecific (X. malinche) on opposite sides of an aquarium. The virtual male stimulus was programmed to track the horizontal position of the female, as courting males do in the wild. Mate-choice trials on wild-caught X. birchmanni females were used to validate the prototype's ability to effectively generate a realistic visual stimulus. PMID:21339726

  19. 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

    Lenartowicz, Małgorzata; Starzyński, Rafał; Wieczerzak, Krzysztof; Krzeptowski, Wojciech; Lipiński, Paweł; Styrna, Józefa

    2011-01-01

    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

  20. 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 Central

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

    2015-01-01

    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

  1. Vascular targets for cannabinoids: animal and human studies

    PubMed Central

    Stanley, Christopher; O'Sullivan, Saoirse E

    2014-01-01

    Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1, CBe, TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6 PMID:24329566

  2. Studying synchronization to a musical beat in nonhuman animals.

    PubMed

    Patel, Aniruddh D; Iversen, John R; Bregman, Micah R; Schulz, Irena

    2009-07-01

    The recent discovery of spontaneous synchronization to music in a nonhuman animal (the sulphur-crested cockatoo Cacatua galerita eleonora) raises several questions. How does this behavior differ from nonmusical synchronization abilities in other species, such as synchronized frog calls or firefly flashes? What significance does the behavior have for debates over the evolution of human music? What kinds of animals can synchronize to musical rhythms, and what are the key methodological issues for research in this area? This paper addresses these questions and proposes some refinements to the "vocal learning and rhythmic synchronization hypothesis." PMID:19673824

  3. Animal models for studying dengue pathogenesis and therapy.

    PubMed

    Chan, Kitti Wing Ki; Watanabe, Satoru; Kavishna, Ranmali; Alonso, Sylvie; Vasudevan, Subhash G

    2015-11-01

    Development of a suitable animal model for dengue virus disease is critical for understanding pathogenesis and for preclinical testing of antiviral drugs and vaccines. Many laboratory animal models of dengue virus infection have been investigated, but the challenges of recapitulating the complete disease still remain. In this review, we provide a comprehensive coverage of existing models, from man to mouse, with a specific focus on recent advances in mouse models for addressing the mechanistic aspects of severe dengue in humans. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery. PMID:26304704

  4. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

    PubMed Central

    Landsteiner, K.; Di Somma, A. A.

    1938-01-01

    With the view of making new types of chemicals accessible for investigations on drug hypersensitiveness, methods have been devised for sensitizing animals with diazomethane and mustard oil, two non-aromatic compounds. Guinea pigs have been sensitized to diazomethane, a substance of high reactivity and known to cause severe allergic effects in man. With the second substance, allylisothiocyanate, likewise capable of forming conjugates with substances in the animal body, sensitization effects have been obtained in man and in hogs. Sensitization in human beings was successful with one out of six individuals treated. The observations indicate species and individual differences as regards the ability to become sensitized to various chemical compounds. PMID:19870801

  5. Using improved serial blood sampling method of mice to study pharmacokinetics and drug-drug interaction.

    PubMed

    Watanabe, Ayahisa; Watari, Ryosuke; Ogawa, Keiko; Shimizu, Ryosuke; Tanaka, Yukari; Takai, Nozomi; Nezasa, Ken-ichi; Yamaguchi, Yoshitaka

    2015-03-01

    In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8 ± 4.0% and 64.4%, fexofenadine: 6.5 ± 0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies. PMID:25452230

  6. Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice

    PubMed Central

    Liu, Haitao; Patel, Shyam; Roberts, Robin; Berkowitz, Bruce A.; Kern, Timothy S.

    2015-01-01

    Objective Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test the hypothesis that photobiomodulation (PBM) is effective in diabetic, pigmented mice, even when delayed until weeks after onset of diabetes. Direct and indirect effects of PBM on the retina also were studied. Methods Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured. In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase-1. In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months. These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo. Results PBM intervention improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers. Conclusions PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention. Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic retinopathy. PMID:26426815

  7. Haemolysis and perturbations in the systemic iron metabolism of suckling, copper-deficient mosaic mutant mice - an animal model of Menkes disease.

    PubMed

    Lenartowicz, Małgorzata; Starzyński, Rafał R; Krzeptowski, Wojciech; Grzmil, Paweł; Bednarz, Aleksandra; Ogórek, Mateusz; Pierzchała, Olga; Staroń, Robert; Gajowiak, Anna; Lipiński, Paweł

    2014-01-01

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

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

    PubMed Central

    Lenartowicz, Małgorzata; Starzyński, Rafał R.; Krzeptowski, Wojciech; Grzmil, Paweł; Bednarz, Aleksandra; Ogórek, Mateusz; Pierzchała, Olga; Staroń, Robert; Gajowiak, Anna; Lipiński, Paweł

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Mehta, Rahul; Lane, Ryan A.; Fitch, Hannah M.; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2009-03-01

    Microgravity has profound effects on skeletal as well as other body systems. To investigate the effect of microgravity, we have used a NASA validated Hind-limb suspension (HLS) animal model of simulated weightlessness. Groups of mice and rats were subjected to hind limb suspension between 1 and 14 days while the control groups were maintained without suspension for the same duration. To study the effect of diet, some groups of animals were fed on a special diet with defined composition. At term, the animals were sacrificed and the tibia, femur, and skull bones were collected. In addition, soft tissues from pancreas and muscles were also collected. All of the bones and tissues samples were analyzed for elemental analysis using Energy Dispersive Spectroscopy (EDS) equipped on a Scanning Electron Microscope (SEM). In the EDS, 10-20 keV electrons bombarded the samples and a Si (Li) detector measured K-, L- and M-shell x-rays. Independently, X-Ray Fluorescence (XRF) provided the data for comparison and normalization. Flame software, with Fuzzy Logic, was used to form elemental ratios. Elemental analysis of bone samples indicated a variation in the compositional ratios of calcium, potassium, oxygen and carbon in the leg bones and skulls of the HLS versus control specimens. These variations showed dependence on sample position in the bone.

  10. Markerless 3D motion capture for animal locomotion studies

    PubMed Central

    Sellers, William Irvin; Hirasaki, Eishi

    2014-01-01

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

  11. [Animal models for the study of Helicobacter pylori infection].

    PubMed

    Miszczyk, Eliza; Walencka, Maria; Mikołajczyk-Chmiela, Magdalena

    2014-01-01

    The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural history of H. pylori infection. Preclinical investigations on animal models are an essential stage of research which enrich the knowledge on treatment and prevention strategies. PMID:24864111

  12. Animal models to study neonatal nutrition in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Markerless 3D motion capture for animal locomotion studies.

    PubMed

    Sellers, William Irvin; Hirasaki, Eishi

    2014-01-01

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

  14. Road-Killed Animals as Resources for Ecological Studies.

    ERIC Educational Resources Information Center

    Adams, Clark E.

    1983-01-01

    Summarizes 19 literature sources identifying road-killed vertebrates and frequency of kill by numbers. Examples of how these animals can be incorporated into curricula (integrating biology, society, people, and values) are given, followed by an illustrated example of how a road-killed raccoon's skull demonstrated a human/wildlife interaction prior…

  15. Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

    SciTech Connect

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

    1987-11-01

    Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg. Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppM. In the 200- and 1000-ppM exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene.

  16. Wnt Signaling in Cartilage Development and Diseases: Lessons from Animal Studies

    PubMed Central

    Usami, Yu; Gunawardena, Aruni T.; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2016-01-01

    Cartilage not only plays essential roles in skeletal development and growth during pre-and post-natal stages but also serves to provide smooth movement of skeletons throughout life. Thus dysfunction of cartilage causes a variety of skeletal disorders. Results from animal studies reveal that β-catenin-dependent canonical and independent non-canonical Wnt signaling pathways have multiple roles in regulation of cartilage development, growth and maintenance. β-catenin-dependent signaling is required for progression of endochondral ossification and growth of axial and appendicular skeletons while excessive activation of this signaling can cause severe inhibition of initial cartilage formation and growth plate organization and function in mice. In contrast, non-canonical Wnt signaling is important in columnar organization of growth plate chondrocytes. Manipulation of Wnt signaling causes or ameliorates articular cartilage degeneration in rodent osteoarthritis models. Human genetic studies indicate that Wnt/β-catenin signaling is a risk factor for osteoarthritis. Accumulative findings from analysis of expression of Wnt signaling molecules and in vivo and in vitro functional experiments suggest that Wnt signaling is a therapeutic target for osteoarthritis. The target tissues of Wnt signaling may be not only articular cartilage but also synovium and subchondral bone. PMID:26641070

  17. Wnt signaling in cartilage development and diseases: lessons from animal studies.

    PubMed

    Usami, Yu; Gunawardena, Aruni T; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2016-02-01

    Cartilage not only plays essential roles in skeletal development and growth during pre- and postnatal stages but also serves to provide smooth movement of skeletons throughout life. Thus, dysfunction of cartilage causes a variety of skeletal disorders. Results from animal studies reveal that β-catenin-dependent canonical and independent non-canonical Wnt signaling pathways have multiple roles in regulation of cartilage development, growth, and maintenance. β-Catenin-dependent signaling is required for progression of endochondral ossification and growth of axial and appendicular skeletons, while excessive activation of this signaling can cause severe inhibition of initial cartilage formation and growth plate organization and function in mice. In contrast, non-canonical Wnt signaling is important in columnar organization of growth plate chondrocytes. Manipulation of Wnt signaling causes or ameliorates articular cartilage degeneration in rodent osteoarthritis models. Human genetic studies indicate that Wnt/β-catenin signaling is a risk factor for osteoarthritis. Accumulative findings from analysis of expression of Wnt signaling molecules and in vivo and in vitro functional experiments suggest that Wnt signaling is a therapeutic target for osteoarthritis. The target tissues of Wnt signaling may be not only articular cartilage but also synovium and subchondral bone. PMID:26641070

  18. Mice lacking the serotonin 5-HT2B receptor as an animal model of resistance to selective serotonin reuptake inhibitors antidepressants.

    PubMed

    Diaz, Silvina Laura; Narboux-Nême, Nicolas; Boutourlinsky, Katia; Doly, Stéphane; Maroteaux, Luc

    2016-02-01

    Depressive disorders are among the most prevalent neuropsychiatric dysfunctions worldwide, with high rates of resistance to antidepressant treatment. Genetic factors clearly contribute to the manifestation of depression as well as to the response to antidepressants. Transgenic mouse models appear as seminal tools to disentangle this complex disorder. Here, we analyzed new key aspects of the phenotype of knock-out mice for the gene encoding the serotonin 2B receptor (Htr2B(-/-)), including basal phenotype, ability to develop a depressive-like phenotype upon chronic isolation, and effect of chronic exposure to fluoxetine on chronically stressed Htr2B(-/-) mice. We find, here, that Htr2B(-/-) mice display an antidepressant-like phenotype, which includes reduced latency to feed in the novelty suppressed feeding test, basal increase in hippocampal BDNF levels, no change in TrkB and p75 protein levels, and an increased preference for sucrose consumption compared to wild type (Htr2B(+/+)) mice. Nevertheless, we show that these mice can develop depressive-like behaviors when socially isolated during four weeks. Selective serotonin reuptake inhibitors (SSRI) have been previously shown to be ineffective in non-stressed Htr2B(-/-) mice. We evaluated, here, the effects of the SSRI fluoxetine in chronically stressed Htr2B(-/-) mice and similarly no behavioral or plastic effect was induced by this antidepressant. All together, these results highlight the suitability to study resistance to SSRI antidepressants of this mouse model displaying panoply of conditions among which behavioral, neurotrophic and plastic causative factors can be analyzed. PMID:26727039

  19. Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: implications for Alzheimer’s disease

    PubMed Central

    Dikranian, Krikor; Kim, Jungsu; Stewart, Floy R; Levy, Marilyn A; Holtzman, David M

    2012-01-01

    Alzheimer’s disease is characterized in part by extracellular aggregation of the amyloid-β peptide in the form of diffuse and fibrillar plaques in the brain. Electron microscopy (EM) has made an important contribution in understanding of the structure of amyloid plaques in humans. Classical EM studies have revealed the architecture of the fibrillar core, characterized the progression of neuritic changes, and have identified the neurofibrillary tangles formed by paired helical filaments (PHF) in degenerating neurons. Clinical data has strongly correlated cognitive impairment in AD with the substantial synapse loss observed in these early ultrastructural studies. Animal models of AD-type brain amyloidosis have provided excellent opportunities to study amyloid and neuritic pathology in detail and establish the role of neurons and glia in plaque formation. Transgenic mice overexpressing mutant amyloid precursor protein (APP) alone with or without mutant presenilin 1 (PS1), have shown that brain amyloid plaque development and structure grossly recapitulate classical findings in humans. Transgenic APP/PS1 mice expressing human apolioprotein E isoforms also develop amyloid plaque deposition. However no ultrastructural data has been reported for these animals. Here we show results from detailed EM analysis of amyloid plaques in APP/PS1 mice expressing human isoforms of ApoE and compare these findings with EM data in other transgenic models and in human AD. Our results show that similar to other transgenic animals, APP/PS1 mice expressing human ApoE isoforms share all major cellular and subcellular degenerative features and highlight the identity of the cellular elements involved in Aβ deposition and neuronal degeneration. PMID:22949930

  20. Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: implications for Alzheimer's disease.

    PubMed

    Dikranian, Krikor; Kim, Jungsu; Stewart, Floy R; Levy, Marilyn A; Holtzman, David M

    2012-01-01

    Alzheimer's disease is characterized in part by extracellular aggregation of the amyloid-β peptide in the form of diffuse and fibrillar plaques in the brain. Electron microscopy (EM) has made an important contribution in understanding of the structure of amyloid plaques in humans. Classical EM studies have revealed the architecture of the fibrillar core, characterized the progression of neuritic changes, and have identified the neurofibrillary tangles formed by paired helical filaments (PHF) in degenerating neurons. Clinical data has strongly correlated cognitive impairment in AD with the substantial synapse loss observed in these early ultrastructural studies. Animal models of AD-type brain amyloidosis have provided excellent opportunities to study amyloid and neuritic pathology in detail and establish the role of neurons and glia in plaque formation. Transgenic mice overexpressing mutant amyloid precursor protein (APP) alone with or without mutant presenilin 1 (PS1), have shown that brain amyloid plaque development and structure grossly recapitulate classical findings in humans. Transgenic APP/PS1 mice expressing human apolioprotein E isoforms also develop amyloid plaque deposition. However no ultrastructural data has been reported for these animals. Here we show results from detailed EM analysis of amyloid plaques in APP/PS1 mice expressing human isoforms of ApoE and compare these findings with EM data in other transgenic models and in human AD. Our results show that similar to other transgenic animals, APP/PS1 mice expressing human ApoE isoforms share all major cellular and subcellular degenerative features and highlight the identity of the cellular elements involved in Aβ deposition and neuronal degeneration. PMID:22949930

  1. Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease

    PubMed Central

    Church, Stephanie J.; Begley, Paul; Kureishy, Nina; McHarg, Selina; Bishop, Paul N.; Bechtold, David A.; Unwin, Richard D.; Cooper, Garth J.S.

    2015-01-01

    Ob/ob mice provide an animal model for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) in patients with obesity and type-2 diabetes. Low liver copper has been linked to hepatic lipid build-up (steatosis) in animals with systemic copper deficiency caused by low-copper diets. However, hepatic copper status in patients with NAFLD or NASH is uncertain, and a validated animal model useful for the study of hepatic copper regulation in common forms of metabolic liver disease is lacking. Here, we report parallel measurements of essential metal levels in whole-liver tissue and defatted-dried liver tissue from ob/ob and non-obese control mice. Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model. By marked contrast, metal measurements in defatted-dried liver samples reveal that most essential metals were actually normal and indicate specific lowering of copper in ob/ob mice, consistent with hepatic copper deficiency. Thus ob/ob mice can provide a model useful for the study of copper regulation in NAFLD and NASH, provided levels are measured in defatted-dried liver tissue. PMID:25797622

  2. Peromyscus mice as a model for studying natural variation.

    PubMed

    Bedford, Nicole L; Hoekstra, Hopi E

    2015-01-01

    The deer mouse (genus Peromyscus) is the most abundant mammal in North America, and it occupies almost every type of terrestrial habitat. It is not surprising therefore that the natural history of Peromyscus is among the best studied of any small mammal. For decades, the deer mouse has contributed to our understanding of population genetics, disease ecology, longevity, endocrinology and behavior. Over a century's worth of detailed descriptive studies of Peromyscus in the wild, coupled with emerging genetic and genomic techniques, have now positioned these mice as model organisms for the study of natural variation and adaptation. Recent work, combining field observations and laboratory experiments, has lead to exciting advances in a number of fields-from evolution and genetics, to physiology and neurobiology. PMID:26083802

  3. Peromyscus mice as a model for studying natural variation

    PubMed Central

    Bedford, Nicole L; Hoekstra, Hopi E

    2015-01-01

    The deer mouse (genus Peromyscus) is the most abundant mammal in North America, and it occupies almost every type of terrestrial habitat. It is not surprising therefore that the natural history of Peromyscus is among the best studied of any small mammal. For decades, the deer mouse has contributed to our understanding of population genetics, disease ecology, longevity, endocrinology and behavior. Over a century's worth of detailed descriptive studies of Peromyscus in the wild, coupled with emerging genetic and genomic techniques, have now positioned these mice as model organisms for the study of natural variation and adaptation. Recent work, combining field observations and laboratory experiments, has lead to exciting advances in a number of fields—from evolution and genetics, to physiology and neurobiology. DOI: http://dx.doi.org/10.7554/eLife.06813.001 PMID:26083802

  4. Study on the Establishment of Heilongjiang Provinces Animal Husbandry Basic Data Platform Based on Data Warehouse

    NASA Astrophysics Data System (ADS)

    Zheng, Ping; Su, Zhongbin; Zhang, Jicheng

    The paper establishes animal husbandry information service platform, and the public data platform of animal husbandry is based on data warehouse platform. It aims at the absence of effective use of data resources issues in the process of animal husbandry information. Then it studies on the key technology for the animal husbandry. It will be of the theoretical basis for information integration, storing, sharing and analysis decision-making.

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

    PubMed

    Simon, Lacey C; Sabliov, Cristina M

    2014-05-01

    A review of poly(lactic-co-glycolic) acid (PLGA) nanoparticle (NP) biodistribution was conducted with the intent of identifying particle behavior for drug delivery applications. Databases such as Science Direct and Web of Science were used to locate papers on biodistribution of intravenous (i.v.) and orally delivered PLGA NPs in mice and rats. The papers included in the review were limited to those that report biodistribution data in terms of % dose particles/g tissue in the liver, kidney, spleen, lung, heart and brain. Noted trends involved particle behavior based on individual organ, particle size, animal model, type of indicator (entrapped versus covalently linked) and method of delivery (oral or i.v.). The liver showed the highest uptake of particles in mice, and the lung showed the highest uptake in rats. Minimal amounts of particles were detected in both the heart and brain of rats and mice. In rats, the concentration of particles approached 0% dose/g or decreased significantly over 24 h after administration of a single dose of particles. Higher concentrations of smaller particles were evident in the liver, kidney and spleen. Orally delivered drugs showed little to no uptake within the 24 h analysis when compared with i.v. delivered NPs. Differences in particle concentrations between rats and mice were also observed as expected when expressed as % dose/g organ. Particles with covalently linked indicators showed lower concentrations in tissues than particles with physically entrapped indicators. Further research on oral delivery of PLGA NPs as well as distribution beyond 24 h is needed to fully understand particle behavior in vivo for successful application of NPs in drug delivery. PMID:24303927

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

    EPA Science Inventory

    Animal models for studying miscarriage: Illustration with study of drinking water disinfection by-products
    Authors & affiliations:
    Narotsky1, M.G. and S. Bielmeier Laffan2.
    1Reproductive Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Tri...

  7. In Vivo Toxicity Studies of Europium Hydroxide Nanorods in Mice

    PubMed Central

    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

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

  8. In vivo toxicity studies of europium hydroxide nanorods in mice

    SciTech Connect

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

    2009-10-01

    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.

  9. Making an animal model for Korean mummy studies.

    PubMed

    Oh, Chang Seok; Shin, Dong Hoon

    2014-01-01

    The recent findings of a series of thorough investigations into Korean mummies notwithstanding, many questions on the exact mechanism of the mummification process remain. For the purposes of a more comprehensive understanding of this mechanism, we employed an animal model involving Sprague-Dawley rats and miniature lime-soil-mixture barrier (LSMB)-surrounded Joseon tombs constructed in our lab. The results showed that long-duration burial in these LSMB tombs successfully induced animal mummification. Indeed, our gross and microscopic examinations confirmed that the rats were perfectly mummified in the manner of actual Korean mummies dating to the Joseon period. In light of the fact that the extent of mummification was not remarkable in other miniature tombs without LSMB, it seemed that the LSMB is somehow closely correlated with mummification in Korea. In the future, use of the present animal models and miniature tombs no doubt will experimentally verify the many possible factors operative in the specific mechanism of mummification in Korea. PMID:25774982

  10. Collective behavior in animal groups: theoretical models and empirical studies

    PubMed Central

    Giardina, Irene

    2008-01-01

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

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

    SciTech Connect

    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

    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.

  12. Modality comparison for small animal radiotherapy: A simulation study

    SciTech Connect

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

    2014-01-15

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

  13. Modality comparison for small animal radiotherapy: A simulation study

    SciTech Connect

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

    2014-01-15

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

  14. Modality comparison for small animal radiotherapy: A simulation study

    PubMed Central

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

    2014-01-01

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

  15. Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.

    PubMed

    Serafín, Anna; Molín, Jessica; Márquez, Merce; Blasco, Ester; Vidal, Enric; Foradada, Laia; Añor, Sonia; Rabanal, Rosa M; Fondevila, Dolors; Bosch, Fàtima; Pumarola, Martí

    2010-05-01

    Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy. PMID:19918773

  16. Use of Transgenic and Mutant Animal Models in the Study of Heterocyclic Amine-induced Mutagenesis and Carcinogenesis

    PubMed Central

    Dashwood, Roderick H.

    2008-01-01

    Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptΔ transgenics, XPA−/−, XPC−/−, Msh2+/−, Msh2−/− and p53+/− knock-outs, Apc mutant mice (ApcΔ716, Apc1638N, Apcmin), and A33ΔNβ-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac. PMID:12542973

  17. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but with a much diminished virulence potential. PMID:26446423

  18. Insights from the Study of Animals Lacking Functional Estrogen Receptor

    NASA Astrophysics Data System (ADS)

    Korach, Kenneth S.

    1994-12-01

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

  19. Animal Models Used to Study Superantigen-Mediated Diseases.

    PubMed

    Brosnahan, Amanda J

    2016-01-01

    Superantigens secreted by Staphylococcus aureus and Streptococcus pyogenes interact with the T-cell receptor and major histocompatibility class II molecules on antigen-presenting cells to elicit a massive cytokine release and activation of T cells in higher numbers than that seen with ordinary antigens. Because of this unique ability, superantigens have been implicated as etiological agents for many different types of diseases, including toxic shock syndrome, infective endocarditis, pneumonia, and inflammatory skin diseases. This review covers the main animal models that have been developed in order to identify the roles of superantigens in human disease. PMID:26676033

  20. Second hand smoke and COPD: lessons from animal studies

    PubMed Central

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

    2013-01-01

    Exposure to second hand smoke is a major cause of chronic obstructive pulmonary disease (COPD) in the non-smoker. In this review we explore the use of animal smoke exposure models and their insight into disease pathogenesis. The methods of smoke exposure, including exposure delivery systems, are described. Key findings from the acute and chronic smoke exposure models are outlined, including descriptions of the inflammation processes, proteases involved, oxidative stress, and apoptosis. Finally, alternatives to rodent models of lung disease are presented. PMID:23450717

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

    PubMed Central

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

    2010-01-01

    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

  2. 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...

  3. CYTOGENETIC STUDIES OF ETHYL ACRYLATE USING C57BL/6 MICE

    EPA Science Inventory

    The clastogenicity of ethyl acrylate (EA) was examined in vivo by injecting i.p. 5 male C57BL/6 mice per dose group with either 125, 250, 500, 1000 mg/kg EA dissolved in saline. wenty-four hours after injection, the animals were anesthetized, the spleens aseptically removed, and ...

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

    ERIC Educational Resources Information Center

    Worsham, Lynn

    2013-01-01

    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…

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

    ERIC Educational Resources Information Center

    Worsham, Lynn

    2013-01-01

    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

  6. Effect of low-level laser therapy on irradiated parotid glands—study in mice

    NASA Astrophysics Data System (ADS)

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028 cm2, 3.57 W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71 J/cm2) or 4 J (40 s, 135 J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  7. A morphologic study of Fluorogold labeled tensor tympani motoneurons in mice.

    PubMed

    Mukerji, Sudeep; Brown, M Christian; Lee, Daniel J

    2009-06-30

    The tensor tympani is one of two middle ear muscles that regulates the transmission of sound through the middle ear. Contraction of the tensor tympani in response to both auditory and non-auditory stimulation is mediated by the tensor tympani motoneurons (TTMNs). There are interesting differences among species in the acoustic thresholds for contraction of the middle ear muscles, which may be a reflection of underlying anatomical differences such as the number of TTMNs. However anatomical data for mice are lacking, even though the mouse is becoming the most common animal model for auditory and neuroscience research. We investigated the number and morphology of TTMNs in mice using Fluorogold, a retrograde neuronal tracer. After injections of Fluorogold into the tensor tympani muscle, a column of labeled TTMNs was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: "octopus-like", "fusiform" and "stellate", suggesting underlying differences in function. All three subtypes formed sparsely branched and radiating dendrites, some longer than 600 microm. Dendrites were longest and most numerous in the dorso-medial direction. In 18 cases, the mean number of mouse TTMNs was 51; the largest numbers were 70, 74 and 90 (n=3 injections). The mean size of mouse TTMNs was 13.0 microm (minor axis) and 23.5 microm (major axis). Compared with studies of TTMNs in larger species (cats and rats), mouse TTMNs are both fewer in number and smaller in size. PMID:19397898

  8. Preflight studies on tolerance of pocket mice to oxygen and heat. II - Effects on lungs

    NASA Technical Reports Server (NTRS)

    Harrison, G. A.; Corbett, R. L.; Klein, G.

    1975-01-01

    An electron microscope examination was carried out on the lungs of 11 pocket mice (Perognathus longimembris) that breathed oxygen at 10 psi or 12 psi partial pressure over a period of 7 d, at the end of which time they were decompressed to sea-level O2 pressure, either suddenly or in 30, 60, or 90 min. Vesiculation was noted in the endothelium of the alveolar-capillary wall in most of the animals and, occasionally, blebbing. Some mitochrondria were swollen in a few of the animals. Alveolar exudate was, in general, sparse. Compared with the lungs of other rodents, the lungs of pocket mice appeared relatively resistant to the toxic effects of oxygen. This conclusion needs, however, to be tempered by the fact that 5% N2 was used in the tests reported here. Nonetheless, the results suggest that the oxygen pressures anticipated on the flight of Apollo XVII should be well tolerated by the pocket mice.

  9. Micronucleus studies in the peripheral blood and bone marrow of mice treated with jet fuels, JP-8 and Jet-A.

    PubMed

    Vijayalaxmi; Kligerman, Andrew D; Prihoda, Thomas J; Ullrich, Stephen E

    2006-09-19

    The potential adverse effects of dermal and inhalation exposure of jet fuels are important for health hazard evaluation in humans. The genotoxic potential of jet fuels, JP-8 and Jet-A, was investigated in an animal model. Mice were treated dermally with either a single or multiple applications of these jet fuels. Peripheral blood and bone marrow smears were prepared to examine the incidence of micronuclei (MN) in polychromatic erythrocytes (PCEs). In all experiments, using several different exposure regimens, no statistically significant increase in the incidence of MN was observed in the bone marrow and/or peripheral blood of mice treated with JP-8 or Jet-A when compared with those of untreated control animals. The data in mice treated with a single dose of JP-8 or Jet-A did not confirm the small but statistically significant increase in micronuclei reported in our previous study. PMID:16815737

  10. A cognitive behaviorist approach to the study of animal behavior.

    PubMed

    Zentall, Thomas R

    2002-10-01

    Traditional psychological approaches to animal learning and behavior have involved either the atheoretical behaviorist approach proposed by B. F. Skinner (1938), in which input-output relations are described in response to environmental manipulations, or the theoretical behaviorist approach offered by C. L Hull (1943), in which associations mediated by several hypothetical constructs and intervening variables are formed between stimuli and responses. Recently, the application of a cognitive behaviorist approach to animal learning and behavior has been found to have considerable value as a research tool. This perspective has grown out of E. C. Tolman's cognitive approach to learning in which behavior is mediated by mechanisms that are not directly observable but can be inferred from the results of critical experiments. In the present article, the author presents several examples of the successful application of the cognitive behaviorist approach. In each case, the experiments have been designed to distinguish between more traditional mechanisms and those mediated by hypothesized internal representations. These examples were selected because the evidence suggests that some form of active cognitive organization is needed to account for the behavioral results. PMID:12494989

  11. Influence of genetic composition of test-animal populations on chronic toxicity studies used for risk estimation.

    PubMed

    Littlefield, N A; Wolff, G L; Nelson, C J

    1985-01-01

    A lifespan exposure of mice to benzidine dihydrochloride was conducted for 33 m using both sexes of two populations of mice with the same gene pool. One population was the genetically homogeneous F1 hybrid produced by crossing BALB/cStCrlC3Hf/Nctr males with C57BL/6jfC3Hf/Nctr females. The second population consisted of genetically heterogenous monohybrid cross (MC) offspring produced by mating the F1 hybrids inter se. Data comparisons were made to determine if gene distribution among members of a population affects the response to a toxic insult. Endpoints tested consisted of mortality, liver tumor incidence and time of tumor onset, mortality from reticulum-cell sarcoma, and body weights. In most instances it was noted that among animals not dosed (controls), the F1 population had lower background incidence of lesions and lived longer than the MC population. However, among the dosed animals, the F1 mice were generally more susceptible to the toxic agent and developed higher incidences of the chemically induced lesions than did the MC population. The F1 hybrid population gave a more conservative estimate of risk than did the MC population. The calculation of the liver tumor risk for these two populations showed that lifespan exposure to benzidine would be predicted to result in a larger number (higher risk) when using the F1 data. A 4.5-fold difference in the toxic response was observed between the F1 females and the MC males. This emphasizes the importance of gene distribution in risk estimation studies. PMID:4032486

  12. Influence of genetic composition of test-animal populations on chronic toxicity studies used for risk estimation

    SciTech Connect

    Littlefield, N.A.; Wolff, G.L.; Nelson, C.J.

    1985-01-01

    A lifespan exposure of mice to benzidine dihydrochloride was conducted for 33 m using both sexes of two populations of mice with the same gene pool. One population was the genetically homogeneous F/sub 1/ hybrid produced by crossing BALB/cStCrlC3Hf/Nctr males with C57BL/6JfC3Hf/Nctr females. The second population consisted of genetically heterogenous monohybrid cross (MC) offspring produced by mating the F/sub 1/ hybrids inter se. Data comparisons were made to determine if gene distribution among members of a population affects the response to a toxic insult. Endpoints tested consisted of mortality, liver tumor incidence and time of tumor onset, mortality from reticulum-cell sarcoma, and body weights. In most instances it was noted that among animals not dosed (controls), the F/sub 1/ population has lower background incidence of lesions and lived longer than the MC population. However, among the dosed animals, the F/sub 1/ mice were generally more susceptible to the toxic agent and developed higher incidences of the chemically induced lesions than did the MC population. The F/sub 1/ hybrid population gave a more conservative estimate of risk than did the MC population. The calculation of the liver tumor risk for these two populations showed that lifespan, exposure to benzidine would be predicted to result in a larger number (higher risk) when using the F/sub 1/ data. A 4.5-fold difference in the toxic response was observed between the F/sub 1/ females and the MC males. This emphasizes the importance of gene distribution in risk estimation studies.

  13. Plants or Animals-Which do Junior High School Students Prefer to Study?

    ERIC Educational Resources Information Center

    Wandersee, James H.

    1986-01-01

    Determined if junior high school students prefer to study plants or animals and if their preferences are related to variables of grade level and/or sex. Findings show that, overall, students prefer animal study over plant study. Other findings (such as girls having a greater interest in biological topics than boys) are discussed. (JN)

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

    PubMed Central

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

    2014-01-01

    Objective In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute to arterial blood pressure regulation by producing membrane hyperpolarization and smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary circulation is not fully established. Using mice with genetically encoded deficit of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension. Approach and Result Male wild type and KCa3.1−/−/KCa2.3T/T(+DOX) mice were exposed to chronic hypoxia for four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The KCa3.1−/−/KCa2.3T/T(+DOX) mice developed structural alterations in the heart with increased right ventricular wall thickness as well as in pulmonary vessels with increased lumen size in partially- and fully-muscularized vessels and decreased wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated the gene expression of the KCa2.3 channel by twofold in wild type mice and increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was reduced by 2.5-fold in chronic hypoxic mice of either genotype. Conclusion Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia-induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and increased NS309-induced relaxation in wild-type mice point to a novel mechanism to counteract pulmonary hypertension and to a potential therapeutic utility of KCa2.3/KCa3.1 activators for the treatment of pulmonary hypertension. PMID:24858807

  15. Preflight studies on tolerance of pocket mice to oxygen and heat. IV - Observations on the brain

    NASA Technical Reports Server (NTRS)

    Bailey, O. T.; Ordy, J. M.; Haymaker, W.

    1975-01-01

    Experiments designed to ascertain the effects of oxygen at 8, 10, and 12 psi partial pressure on the brains of pocket mice (Perognathus longimembris) were carried out at room temperature (24 C, 75 F) and at 32 C (90 F). The animals exposed to 8-12 psi at 32 C had been in earlier KO2 oxygen tests. Five animals exposed either to 10 or 12 psi (517 mm or 620 mm Hg) O2 partial pressure at 32 C died during the course of the tests, possibly as a consequence of injury sustained by the earlier O2 partial pressure testing. Autopsy was not carried out. In the other 36 exposed animals, no pathological changes were observed in the brain. It is thus highly probable that oxygen pressures at the hyperbaric levels to which the pocket mice would be exposed during the Apollo XVII mission would not result in any lesions in the brain.

  16. FoxO3a-mediated autophagy is down-regulated in the laforin deficient mice, an animal model for Lafora progressive myoclonus epilepsy.

    PubMed

    Jain, Navodita; Mishra, Rohit; Ganesh, Subramaniam

    2016-05-27

    Lafora disease (LD) is an autosomal recessive disorder characterized by epileptic seizures, neurodegeneration and accumulation of polyglucosan bodies (Lafora bodies), arising due to defects in either the laforin protein phosphatase or the malin ubiquitin ligase. Among the multiple cellular pathways affected in LD, the specific cause of the autophagy blockade remains unknown. The autophagy impairment however is known to precede the formation of Lafora bodies in the LD mice models. We show here the involvement of a transcription factor, FoxO3a, to be a possible cause for the autophagic defect in cellular and animal models of LD. We find that the expression levels of FoxO3a and its targets Map1LC3b and Atg12 to be at lower levels in laforin-deficient cells and mice. We also find FoxO3a to be regulated indirectly by laforin through the activity of serum/glucocorticoid induced kinase, SGK1. Our results suggest that FoxO3a exerts a negative control over mTOR, and its loss could result in autophagic defects in LD associated with laforin deficiency. PMID:27107699

  17. Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies

    PubMed Central

    Zhang, Mutian; Huang, Minming; Le, Carl; Zanzonico, Pat B; Claus, Filip; Kolbert, Katherine S; Martin, Kyle; Ling, C Clifton; Koutcher, Jason A; Humm, John L

    2009-01-01

    Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, gold standard multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2?0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of ?0.2 mm. In serial animal imaging studies, the positioning reproducibility within ?0.8 mm could be obtained. PMID:18827321

  18. Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies.

    PubMed

    Zhang, Mutian; Huang, Minming; Le, Carl; Zanzonico, Pat B; Claus, Filip; Kolbert, Katherine S; Martin, Kyle; Ling, C Clifton; Koutcher, Jason A; Humm, John L

    2008-10-21

    Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, 'gold standard' multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2-0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of approximately 0.2 mm. In serial animal imaging studies, the positioning reproducibility within approximately 0.8 mm could be obtained. PMID:18827321

  19. Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies

    NASA Astrophysics Data System (ADS)

    Zhang, Mutian; Huang, Minming; Le, Carl; Zanzonico, Pat B.; Claus, Filip; Kolbert, Katherine S.; Martin, Kyle; Ling, C. Clifton; Koutcher, Jason A.; Humm, John L.

    2008-10-01

    Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, 'gold standard' multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2-0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of ~0.2 mm. In serial animal imaging studies, the positioning reproducibility within ~0.8 mm could be obtained.

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

    PubMed

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

    2009-03-01

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

  1. Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study.

    PubMed

    Rafati, Ali; Hoseini, Leila; Babai, Ali; Noorafshan, Ali; Haghbin, Hossein; Karbalay-Doust, Saied

    2015-12-01

    Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P < 0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P < 0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P < 0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P < 0.03). PMID:26770914

  2. Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

    PubMed Central

    Rafati, Ali; Hoseini, Leila; Babai, Ali; Noorafshan, Ali; Haghbin, Hossein; Karbalay-Doust, Saied

    2015-01-01

    Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P < 0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P < 0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P < 0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P < 0.03). PMID:26770914

  3. Dentin as a suitable bone substitute comparable to ß-TCP--an experimental study in mice.

    PubMed

    Bormann, Kai-Hendrik; Suarez-Cunqueiro, Maria Mercedes; Sinikovic, Branko; Kampmann, Andreas; von See, Constantin; Tavassol, Frank; Binger, Thomas; Winkler, Meike; Gellrich, Nils-Claudius; Rücker, Martin

    2012-09-01

    Microvascular supply is of fundamental importance to the survival and integration of grafting. Since the autogenous bone is still the gold standard for osseous augmentation, the aim of this study was to analyze the initial osseous, angiogenic and inflammatory response and subsequent osseointegration after implantation of dentin and beta-tricalcium phosphate (ß-TCP) scaffolds into the calvaria chamber of balb/c mice comparing with bone. The vascularisation of perforated implants of dentin (n=8), ß-TCP (n=8) and isogenic calvarial bone (n=8) displaying pores similar in size and structure was analyzed in vivo using intravital fluorescence microscopy. In additional animals (n=24) the osseointegration of dentin, ß-TCP and bone implants was assessed by fluorochrome sequential labelling of growing bone for up to 12 weeks. Animals without implants served as controls. Intravital fluorescence microscopy revealed that implantation of bone substitutes caused an only mild inflammatory response. Comparable to isogenic bone both dentin and ß-TCP scaffolds were found nearly completely vascularized by day 22 and osseointegrated within 12 weeks. In conclusion, dentin and ß-TCP scaffolds are similar to isogenic bone in terms of inflammatory and neovascularization response, highlighting their potential utility in regeneration of bone defects. PMID:22709891

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

    SciTech Connect

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

    2003-08-26

    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)

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

    NASA Astrophysics Data System (ADS)

    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

    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).

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

    SciTech Connect

    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

    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.

  7. Impact of Gestational Bisphenol A on Oxidative Stress and Free Fatty Acids: Human Association and Interspecies Animal Testing Studies

    PubMed Central

    Veiga-Lopez, Almudena; Pennathur, Subramaniam; Kannan, Kurunthachalam; Patisaul, Heather B.; Dolinoy, Dana C.; Zeng, Lixia

    2015-01-01

    Bisphenol A (BPA) is a high production volume chemical and an endocrine disruptor. Developmental exposures to BPA have been linked to adult metabolic pathologies, but the pathways through which these disruptions occur remain unknown. This is a comprehensive interspecies association vs causal study to evaluate risks posed by prenatal BPA exposure and to facilitate discovery of biomarkers of relevance to BPA toxicity. Samples from human pregnancies during the first trimester and at term, as well as fetal and/or adult samples from prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact of BPA on free fatty acid and oxidative stress dynamics. Mothers exposed to higher BPA during early to midpregnancy and their matching term cord samples displayed increased 3-nitrotyrosine (NY), a marker of nitrosative stress. Maternal samples had increased palmitic acid, which was positively correlated with NY. Sheep fetuses and adult sheep and rats prenatally exposed to a human-relevant exposure dose of BPA showed increased systemic nitrosative stress. The strongest effect of BPA on circulating free fatty acids was observed in adult mice in the absence of increased oxidative stress. This is the first multispecies study that combines human association and animal causal studies assessing the risk posed by prenatal BPA exposure to metabolic health. This study provides evidence of the induction of nitrosative stress by prenatal BPA in both the mother and fetus at time of birth and is thus supportive of the use of maternal NY as a biomarker for offspring health. PMID:25603046

  8. Acute toxicity study of the interaction between titanium dioxide nanoparticles and lead acetate in mice.

    PubMed

    Zhang, Rong; Niu, Yujie; Li, Yawei; Zhao, Chunfang; Song, Bo; Li, Yao; Zhou, Yikai

    2010-07-01

    Titanium dioxide (TiO(2)) is one kind of widely used nanoparticle, which was used as a solid-phase extraction to preconcentrated and measured of lead (Pb) in river water and seawater. However the interaction of nanoparticle TiO(2) and Pb was unknown. The aim of this study is to investigate the potential acute toxicity of the interaction between nanoparticle TiO(2) (50 and 120nm) and lead acetate (PbAC) in adult mice. The animals were randomly divided into six groups: a control group and five treatment groups (TiO(2)-50, TiO(2)-120, PbAC, TiO(2)-50+PbAC and TiO(2)-120+PbAC groups). Suspensions of TiO(2) (5g/kg body weight), PbAC (500mg/kg body weigh) and TiO(2) (5g/kg body weight)+PbAC (500mg/kg body weigh) were administrated to mice via oral gavage, respectively. Seven days later, the animals were sacrificed after being anesthetized by ether. There were no significant changes of the body weight coefficients of liver, kidney and brain. However, the results of liver function and nephrotoxicity examination revealed that there were serious damages to liver and kidney between the group treated with the mix suspension and the one with TiO(2). After the mix suspension treatment, ROS levels were significantly increased in liver but not in kidney, cortex and hippocampus. There were no increase of MDA levels in these tissues, and no activity reductions of SOD and GSH-Px in liver and kidney but in the cortex and hippocampus. Therefore, though our results have not suggested that TiO(2) particle and PbAC have a synergistic acute toxicity in mice after oral administration, PbAC may increase the acute toxicity of TiO(2) nanoparticle in some degree. The potential toxic mechanism maybe related with oxidative damages. PMID:21787629

  9. Prevention of osteopaenia by phyto-oestrogens: animal studies.

    PubMed

    Coxam, Véronique

    2003-06-01

    Osteoporosis has become a major public health problem. Because the biggest culprit in the process of bone loss is oestrogen deficiency, hormone replacement therapy remains the mainstay for prevention, but prophylaxis by this means is limited. Phyto-oestrogens deserve special mention because emerging data support the suggestion that these weakly oestrogenic compounds, present in plants, may prevent bone loss associated with the menopause and thus represent a potential alternative therapy for a range of hormone-dependent conditions, including postmenopausal symptoms. A substantial body of work in animal models in the past few years has provided convincing data for significant improvements in bone mass and other endpoints following feeding with soya. Thus, phyto-oestrogens appear to have potential promise for maintaining or modestly improving bone mass of human subjects when consumed at optimal dosages. However, we must appreciate the limits of the information reached before extrapolating to man and we need to gather more data before health professionals can actively advocate the increased consumption of soya. Indeed, it will be important further to characterise the physiological effects of phyto-oestrogens and their margins of safety. PMID:12725657

  10. Generation of Li combustion aerosols for animal inhalation studies.

    PubMed

    Allen, M D; Greenspan, B J; Briant, J K; Hoover, M D

    1986-07-01

    A system was developed for generating Li aerosols to determine the potential health hazards of postulated accidents associated with the use of Li as a fusion reactor blanket or coolant. The aerosol was generated by sweeping Ar through a stainless steel chamber filled with Li metal that was heated inductively to temperatures up to 1300 degrees C. Argon carried the Li vapor into a burning chamber where it was mixed with air. The reaction of Li vapor with air formed an intense white flame that produced typical branched-chain condensation aerosol particles. This system generated well-controlled concentrations up to 2500 mg/m3 for periods of 4 h. The mass median aeordynamic diameter of the aerosol was approximately 0.66 micron with a geometric standard deviation of 1.5. Aerosols could be generated that were greater than 96% Li2O and LiOH, LiOH.H2O, or Li2CO3 by controlling the CO2 and H2O concentrations in the supply air. The system is currently being used to investigate the acute toxicity of Li combustion aerosols in laboratory animals. PMID:3455403

  11. Animals in the Classroom: A Guide for Teachers. Elementary Science Study.

    ERIC Educational Resources Information Center

    Gillmor, Mary S.; And Others

    This guide is designed to encourage people to keep animals of all kinds in the classroom and to use them in teaching language arts, mathematics, and social studies, as well as science and nature study. The booklet is divided into four sections. The first section contains an account of a year with desert animals in an ungraded classroom of six- to…

  12. SOURCES OF VARIATION IN BASELINE GENE EXPRESSION LEVELS FROM TOXICOGENOMIC STUDY CONTROL ANIMALS ACROSS MULTIPLE LABORATORIES

    EPA Science Inventory

    Variations in study design are typical for toxicogenomic studies, but their impact on gene expression in control animals has not been well characterized. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Scienc...

  13. NTP Toxicology and Carcinogenesis Studies of Polyvinyl Alcohol (CAS No.9002-89-5) in Female B6C3F1 Mice (Intravaginal Studies).

    PubMed

    1998-05-01

    Polyvinyl alcohol is produced primarily for use in textile sizing, adhesives, polymerization aids, and paper coatings. It is also used in surgical drapes, towels, and gauze sponges; protective gloves; cosmetic formulations; topical ophthalmic preparations; plastic sponge implants for reconstructive surgery; and intravaginal contraceptive foam and film. In addition, polyvinyl alcohol is used with magnesium sulfate to dilate the cervix of women prior to induction of labor. It is estimated that hundreds of thousands of women in the United States use an intravaginal product containing polyvinyl alcohol each year. The Food and Drug Administration nominated low-viscosity polyvinyl alcohol for a 2-year study because of concern about the lack of information about the long-term toxic and carcinogenic effects by the intravaginal route. Female B6C3F1 mice received polyvinyl alcohol (approximately 99% pure) in deionized water by intravaginal administration for 30 days or 2 years. 30-DAY STUDY IN MICE: Three groups of 50 female B6C3F1 mice were used in this intravaginal study. The vehicle control group received only 20 &mgr;L of a deionized water vehicle. The other two groups each received 20 &mgr;L of 25% polyvinyl alcohol in deionized water. Animals in one dose group were returned to their cages after dosing; animals in the other dose group were restrained in a vertical nose-down position in restraint bags for several minutes after dosing. Animals were dosed daily for 30 consecutive days. All mice survived to the end of the study. The final mean body weights and body weight gains of dosed mice were similar to those of the vehicle control group. Abnormalities noted in the vaginal area after dosing included vaginal plugs, secretions, and swelling. These vaginal changes were minimal to mild and occurred in vehicle controls as well as in dosed mice. Restraint of mice after dosing appeared to eliminate vaginal secretions but increased both the incidence of vaginal irritation and the severity of vaginal opening swelling. At necropsy, mildly enlarged uterine horns were observed in 10 vehicle control mice, three 25% mice, and seven 25% (restrained) mice. No chemical-related lesions were observed. 2-YEAR STUDY IN MICE: Three groups of 100 female B6C3F1 mice were used in this intravaginal study: an untreated control group, a vehicle control group receiving 20 &mgr;L deionized water vehicle only, and a dosed group receiving 20 &mgr;L 25%% polyvinyl alcohol in deionized water. Animals were dosed 5 days per week, excluding holidays, for 104 to 105 weeks. Survival, Body Weights, and Clinical Findings: Survival of dosed mice was similar to that of the two control groups. The final mean body weight of vehicle control mice was less than that of the untreated control group. The mean body weights of the dosed mice were less than those of the untreated controls from week 17 until the end of the study. The only clinical finding was vaginal irritation, observed in six mice in the vehicle control group and 11 mice in the dosed group. Pathology Findings: No neoplasms or nonneoplastic lesions related to chemical treatment were observed. The incidences of reproductive tract nonneoplastic lesions in the dosed group did not differ significantly from those in the vehicle control group; similarly, the incidences of reproductive tract nonneoplastic lesions in the vehicle control group did not differ significantly from those in the untreated control group. CONCLUSIONS: Under the conditions of this 2-year study, there was no evidence of carcinogenic activity of polyvinyl alcohol (molecular weight approximately 24,000) in female B6C3F1 mice administered 20 &mgr;L of a 25%% solution intravaginally. There were no neoplasms or nonneoplastic lesions considered related to treatment with polyvinyl alcohol. Synonyms: Ethenol homopolymer, PVA Trade names: Akwa Tears, Alcotex, Alvyl, Aracet, Cipoviol, Covol, Elvanol, Ethenol, Gelvatol, Gohsenol, Ivalon, Kuralon, Kurare, Lemol, Liquifilm, Mowiol, Polydesis, Polysizer, Polyvinol, Polyviol, Poval, Resistoflex, Rhodoviol, Sno, Poval, Resistoflex, Rhodoviol, Sno Tears, Solvar, Sumitex, Vibatex, Vinacol, Vinalak, Vinarol, Vinarole, Vinavilol, Vinol, Vinylon PMID:12571676

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

    PubMed

    Galef, Bennett G

    2015-03-01

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

  15. Studies of an expanded trinucleotide repeat in transgenic mice

    SciTech Connect

    Bingham, P.; Wang, S.; Merry, D.

    1994-09-01

    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.

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

    PubMed Central

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

    2014-01-01

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

  17. The usefulness of systematic reviews of animal experiments for the design of preclinical and clinical studies.

    PubMed

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

    2014-01-01

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

  18. [Studies On The Inducing Possibility Of Human Visceral Larva Migrans Associated With Eating Habit Of Raw Liver Of Domestic Animals

    PubMed

    Lee, Keun Tae; Min, Hong Ki; Chung, Pyung Rim; Chang, Jae Kyung

    1976-06-01

    To observe the possibility of human visceral larva migrans due to eating of raw liver of domestic animals, especially of cattle, and also to serve as a good reference for adequate sanitary measures, the investigation survey was carried out from May 1975 to May 1976. From the subjects of a l,048 inhabitants (male 558, female 490) in five localities including two Provinces and three different cities, food habit was studied by questionnaire mannual. Larvae isolated from liver tissues of cattle, and pig were identified. Experimental observation on the chicken and mice infected with Toxocara canis was undertaken to draw a assumption of possibility inducing human visceral larva migrans. The results obtained from the present study are summarized. 1. A part of Korean people has the habit to eat the livers of cattle, fowl, pig and dog raw. Eating rate of raw beef liver was 37.8% out of l,048 inhabitants, and its rate was higher markedly in male(57.7%) than in female (15. 1%), and the highest rate among the group of 31-40 years old. Eating rate of raw liver of fowl was 5.9%, pig 5.3%, and dog 2.5%. 2. Larva recovery rate from beef liver was 11.8% out of 195 samples and 72.0% of total detected 1arvae were identified as Toxocara(=Neoascaris) vitulorum. From pig liver, larvae of nematoda were found in 6.4% out of 109 samples but no larva was detected from 120 fowl livers. 3. Larvae detected from one-half of tissues and organs of infected chicken with about 2,000 Toxocara canis eggs were 8-245 in number, and 85-100% of recovered larvae were from their 1iver tissues. 4. Toxocara canis larvae, 45, 31, 42 and 23 in number at 3rd, 14th, 25th and 55th day in one-half of the tissues and organs after infection respectively, were demonstrated from the mice infected with 500 larvae collected from infected chicken liver. Most of the larvae were recovered from the carcass of the mouse. It was approved the larvae isolated from chicken possess infectivity to the mice. 5. Typical eosinophilic granulomatous change was not observed in the liver tissue of the infected chicken at 20th day after infection. As it summarized above, the liver of various domestic animals is the favorite tissue for migration of nematodes larvae. Therefore, the possibility of human visceral larva migrans may be induced due to eating of raw liver of domestic animals. PMID:12913451

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

    SciTech Connect

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

    1988-08-01

    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.

  20. Role of Human Na,K-ATPase alpha 4 in Sperm Function, Derived from Studies in Transgenic Mice

    PubMed Central

    McDermott, Jeffrey; Sánchez, Gladis; Nangia, Ajay K.; Blanco, Gustavo

    2014-01-01

    SUMMARY Most of our knowledge on the biological role of the testis-specific Na,K-ATPase alpha 4 isoform derives from studies performed in non-human species. Here, we studied the function of human Na,K-ATPase alpha 4 after its expression in transgenic mice. Using a bacterial artificial chromosome (BAC) construct, containing the human ATP1A4 gene locus, we obtained expression of the human α4 transgene specifically in mouse sperm, enriched in the sperm flagellum. The expressed, human alpha 4 was active, and compared to wild-type sperm, those from transgenic mice displayed higher Na,K-ATPase alpha 4 activity and greater binding of fluorescently labeled ouabain, which is typical of the alpha 4 isoform. The expression and activity of endogenous alpha 4 and the other Na,K-ATPase alpha isoform present in sperm, alpha 1, remained unchanged. Male mice expressing the human ATP1A4 transgene exhibited similar testis size and morphology, normal sperm number and shape, and no changes in overall fertility compared to wild-type mice. Sperm carrying the human transgene exhibited enhanced total motility and an increase in multiple parameters of sperm movement, including higher sperm hyperactive motility. In contrast, no statistically significant changes in sperm membrane potential, protein tyrosine phosphorylation, or spontaneous acrosome reaction were found between wild-type and transgenic mice. Altogether, these results provide new genetic evidence for an important role of human Na,K-ATPase alpha 4 in sperm motility and hyperactivation, and establishes a new animal model for future studies of this isoform. PMID:25640246

  1. Passive cutaneous anaphylaxis and vasoactive amine challenge in nude (nu/nu) mice. A comparison with nu/+, axenic and young normal animals.

    PubMed

    Lynch, N R; Prin, J; Salomon, J C

    1977-01-01

    Recent suggestions of a thymic origin or thymo-dependent differentiation of tissue mast cells prompted an investigation in the athymic nude (nu/nu) mouse. The outbred nu/nu examined were found to possess mast cells in at least comparable numbers to the phenotypically normal nu/+. These nu/nu were superior to nu/+ as recipient for mast cell-dependent, long latent period (IgE-type), passive cutaneous anaphylactic (PCA) reactions. A variety of studies performed, including competition with nu/+ serum, thymic restoration, quantitation of nu/+ homocytotropic antibody responses, comparison with axenic or young mice and time-course studies of skin sensitization suggested that the higher PCA titres in nu/nu skin were not entirely due to a lack of competitive inhibition of mast-cell sensitization. The nu/+ used in these studies were in fact poor IgE recipients, but were somewhat more sensitive than nu/nu to hypovolaemic shock induced by histamine and serotonin mixtures. Pretreatment with Bordetella pertussis greatly enhanced the sensitivity of nu/+, axenic, holoxenic and young normal mice to the vasoactive effects of histamine and serotonin, but was somewhat less effective in nu/nu and old mice. PMID:844890

  2. Transgenic mice: beyond the knockout

    PubMed Central

    2011-01-01

    Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interactions using multiple fluorescent proteins in the same mouse, and the cell cycle in real time and in the whole animal, and they can be used to perform deep tissue imaging in the whole animal, follow cell lineage during development and disease, and isolate large quantities of a pure cell type directly from organs. These novel transgenic mice and their applications provide the means for studying of molecular and biochemical events in the whole animal that was previously limited to cell cultures. In conclusion, transgenic mice are not just for generating knockouts. PMID:21068085

  3. Refinements in the care and use of animals in toxicology studies-regulation, validation, and progress.

    PubMed

    Turner, Patricia V; Smiler, Kathleen L; Hargaden, Maureen; Koch, Michael A

    2003-11-01

    During the past decade, important advances have been made in the humane care and use of laboratory animals used in toxicology studies, and there is strong international interest by the pharmaceutical sector in continuing with this progress. Because of the potential influence on human health, safety studies are highly regulated, and implementing refinements in laboratory animal care and use may require an initial validation study to demonstrate a lack of effect on study outcome. This paper provides an overview of issues surrounding implementation of animal care refinements in toxicology laboratory settings, including regulatory constraints, conducting validation studies, current progress in refinements, and areas for future consideration. PMID:14615954

  4. Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals

    PubMed Central

    Niu, Ho-Shan; Ku, Po-Ming; Niu, Chiang-Shan; Cheng, Juei-Tang; Lee, Kung-Shing

    2015-01-01

    Background The development of new drugs for the treatment of diabetes mellitus (DM) is critically important. Insulin resistance (IR) is one of the main problems associated with type-2 DM (T2DM) seen in clinics. GW0742, a selective peroxisome proliferator-activated receptor (PPAR)-δ agonist, has been shown to ameliorate metabolic abnormalities including IR in skeletal muscle in mice fed high-fructose corn syrup. However, the influence of GW0742 on systemic insulin sensitivity has still not been elucidated. Therefore, it is important to investigate the effect of GW0742 on systemic IR in diabetic rats for the development of new drugs. Methods The present study used a T2DM animal model to compare the effect of GW0742 on IR using homeostasis model assessment-IR (HOMA-IR) and hyperinsulinemic euglycemic clamping. Additionally, the insulinotropic action of GW0742 was investigated in type-1 DM (T1DM) rats. Changes in the protein expression of glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and in liver, respectively, were also identified by Western blots. Results GW0742 attenuated the increased HOMA-IR in diabetic rats fed a fructose-rich diet. This action was blocked by GSK0660 at the dose sufficient to inhibit PPAR-δ. Improvement of IR by GW0742 was also characterized in diabetic rats using hyperinsulinemic euglycemic clamping. Additionally, an increase of insulin sensitivity due to GW0742 was observed in these diabetic rats. Moreover, GW0742 reduced the hyperglycemia in T1DM rats lacking insulin. Western blotting analysis indicated that GW0742 reversed the decrease in GLUT4 and markedly reduced the increased PEPCK in liver. Conclusion The data showed that GW0742 has the ability to improve glucose homeostasis in diabetic rats through activation of PPAR-δ. Therefore, PPAR-δ is a good target for the development of antidiabetic drugs in the future. PMID:26508837

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

    PubMed

    Carlstead, Kathy

    2009-11-01

    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

  6. Study on the Antinociceptive Effects of Herba Epimedium in Mice

    PubMed Central

    Sun, Jiang-hong; Ruan, Xin-jie; Wang, Li-na; Liang, Shuang; Li, Xin-ping

    2015-01-01

    The present study was conducted to investigate the antinociceptive action of relationship between Herba Epimedium (HE) and 5-HT1A receptor, between Herba Epimedium (HE) and 5-HT2A receptor. We used the hot-plate method and the writhing assay in mice by the intracerebroventricular (i.c.v.) injection and observed the analgesic effect of HE. Furthermore, through the i.c.v. injection, 5-HT1A receptor partial agonist Buspirone, antagonist Propranolol, the adrenaline β1-receptor selective blocking agent Metoprolol, and 5-HT2A receptor agonist hydrochloride DOI and antagonist Ketanserin were used, and, 5 min later, HE was used to investigate the impacts of drugs on the analgesic effect in the same way. Results showed that HE had fast and significant antinociception in nervous system, and the effects can persist for a long time. Buspirone and Hydrochloride DOI can remarkably increase the antinociception of HE in nervous system. Ketanserin leads to a significant decrease in its antinociception in nervous system; Metoprolol also has antinociceptive action in nervous system, but it can inhibit the antinociceptive effect of Herba Epimediumin peripheral region. These results suggest that HE has significant antinociception effect and its mechanism is related with 5-HT1A receptor, 5-HT2A receptor, and adrenaline β1-receptor. PMID:26170874

  7. Modeling the Study of DNA Damage Responses in Mice

    PubMed Central

    Specks, Julia; Nieto-Soler, Maria; Lopez-Contreras, Andres J; Fernandez-Capetillo, Oscar

    2016-01-01

    Summary Damaged DNA has a profound impact on mammalian health and overall survival. In addition to being the source of mutations that initiate cancer, the accumulation of toxic amounts of DNA damage can cause severe developmental diseases and accelerate ageing. Therefore, understanding how cells respond to DNA damage has become one of the most intense areas of biomedical research in the recent years. However, whereas most mechanistic studies derive from in vitro or in cellulo work, the impact of a given mutation on a living organism is largely unpredictable. For instance, why BRCA1 mutations preferentially lead to breast cancer whereas mutations compromising mismatch repair drive colon cancer is still not understood. In this context, evaluating the specific physiological impact of mutations that compromise genome integrity has become crucial for a better dimensioning of our knowledge. We here describe the various technologies that can be used for modeling mutations in mice, and provide a review of the genes and pathways that have been modeled so far in the context of DNA damage responses. PMID:25636482

  8. Study on the Mechanical Instability of MICE Coupling Magnets

    SciTech Connect

    Wang, Li; Pan, Heng; Gou, Xing Long; Wu, Hong; Zheng, Shi Xian; Green, Michael A

    2011-05-04

    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.

  9. Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

    PubMed

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies. PMID:26528293

  10. Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

    PubMed Central

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

  11. [Radiation exposure of cultured tissue cells and animals (mice) within 10-kilometers zone of accident at Chernobyl nuclear plant. Effect on radiosensitivity to future radiation].

    PubMed

    Pelevina, I I; Afanasév, G G; Gotlib, V Ia; Alferovich, A A; Antoshchina, M M; Riabchenko, N I; Saenko, A S; Riabtsev, I A; Riabov, I N

    1993-01-01

    The effect of chronic low-level radiation exposure on radiosensitivity to posterior acute irradiation at high doses has been studied. Cells and mice were exposed within the ten-kilometer zone of Chernobyl disaster during various spaces of time (1-12 days), then over one or more days were additionally irradiated by doses of 1-4 Gy. It was shown that no adaptive response was developed under chronic exposure of cells and mice within the zone of disaster. On the contrary increased sensitivity to posterior irradiation was revealed. The number of cytogenetic damages of cultured tissue cells and marrow cells (chromosome aberrations and micronuclei) increases, the spectrum of aberrations being shifted to chromosome type, cells with multiaberration appearing. The decay of chromatine increases indicating an interphase death; the number of leucocytes in peripheral blood decreases. PMID:8401871

  12. 3D visualization and quantification of bone and teeth mineralization for the study of osteo/dentinogenesis in mice models

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    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.

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

    PubMed

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

    2014-04-01

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

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

    SciTech Connect

    Germolec, D.R.; Yang, R.S.; Ackermann, M.F.; Rosenthal, G.J.; Boorman, G.A.; Blair, P.; Luster, M.I. )

    1989-10-01

    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.

  15. A Comprehensive Study of Soft Palate Development in Mice

    PubMed Central

    Grimaldi, Alexandre; Parada, Carolina; Chai, Yang

    2015-01-01

    Cleft palate is one of the most common congenital birth defects. Tremendous efforts have been made over the last decades towards understanding hard palate development. However, little is known about soft palate morphogenesis and myogenesis. Finding an appropriate surgical repair to restore physiological functions of the soft palate in patients with cleft palate is a major challenge for surgeons, and complete restoration is not always achievable. Here, we first analyzed the morphology, orientation and attachments of the four muscles of the murine soft palate and found that they are very similar to their counterparts in humans, validating the use of mus musculus as a model for future studies. Our data suggests that muscle differentiation extends from the lateral region to the midline following palatal fusion. We also detected an epithelial seam in the fusing soft palatal shelves, consistent with the process of fusion of the posterior palatal shelves, followed by degradation of the epithelial remnants. Innervation and vascularization are present mainly in the oral side of the soft palate, complementing the differentiated muscles. Cell lineage tracing using Wnt1-Cre;Zsgreenfl/fl mice indicated that all the tendons and mesenchyme embedding the soft palate muscles are neural crest-derived. We propose that the posterior attachment of the soft palate to the pharyngeal wall is an interface between the neural crest- and mesoderm-derived mesenchyme in the craniofacial region, and thus can serve as a potential model for the study of boundaries during development. Taken together, our study provides a comprehensive view of the development and morphology of the murine soft palate and serves as a reference for further molecular analyses. PMID:26671681

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

    ERIC Educational Resources Information Center

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

    2011-01-01

    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…

  17. Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain

    ERIC Educational Resources Information Center

    Enticott, Gareth

    2012-01-01

    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…

  18. Regulating Animal Health, Gender and Quality Control: A Study of Veterinary Surgeons in Great Britain

    ERIC Educational Resources Information Center

    Enticott, Gareth

    2012-01-01

    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

  19. Carcinogenic comparative study on rasH2 mice produced by two breeding facilities.

    PubMed

    Machida, Kazuhiko; Urano, Koji; Yoshimura, Masumi; Tsutsumi, Hideki; Nomura, Tatsuji; Usui, Toshimi

    2008-10-01

    CByB6F1-Tg(HRAS)2Jic mice (brand name: rasH2 mouse) are produced by two breeding facilities, CLEA Japan, Inc. (Fuji, Shizuoka, Japan) and Taconic (Germantown, NY, USA), and supplied world wide. To confirm carcinogenic conformity of both mice, a 26-week carcinogenicity test was performed on a total of 120 mice obtained from both facilities under the same protocol and same timing in our facility. All mice were divided into a vehicle (citrate buffer at pH 4.5, 10 ml/kg, single intraperitoneal injection) group and a MNU (N-methyl-N-nitrosourea, 75 mg/kg, single intraperitoneal injection) group. Fifteen mice of each sex were assigned to each group. The survival rate of the vehicle group was maintained at 100% for mice from both facilities at completion of the test. In the MNU group, MNU-induced tumor death occurred from 9 to 12 weeks after administration, and the final survival rate for both facilities was 6.7%. In the pathological examination, only benign tumors of lungs, spleen, forestomach and skin were observed in a few mice in the vehicle group of both facilities. In the MNU group, the incidence of forestomach papilloma/squamous cell carcinoma in mice from both facilities was 100%. The incidences of malignant lymphoma in CLEA Japan mice and Taconic mice were 86.7% and 93.3%, respectively, and no significant difference was observed (Fisher's exact probability test). Although lung adenoma and skin papilloma/keratoacanthoma, which are major MNU induced tumors in this strain, were observed in several mice from both facilities, no significant differences were found. Consequently, carcinogenic conformity of rasH2 mice derived from two breeding facilities was confirmed by the present study. PMID:18827450

  20. Refining Housing, Husbandry and Care for Animals Used in Studies Involving Biotelemetry

    PubMed Central

    Hawkins, Penny

    2014-01-01

    Simple Summary Biotelemetry, the remote detection and measurement of an animal function or activity, is widely used in animal research. Biotelemetry devices transmit physiological or behavioural data and may be surgically implanted into animals, or externally attached. This can help to reduce animal numbers and improve welfare, e.g., if animals can be group housed and move freely instead of being tethered to a recording device. However, biotelemetry can also cause pain and distress to animals due to surgery, attachment, single housing and long term laboratory housing. This article explains how welfare and science can be improved by avoiding or minimising these harms. Abstract Biotelemetry can contribute towards reducing animal numbers and suffering in disciplines including physiology, pharmacology and behavioural research. However, the technique can also cause harm to animals, making biotelemetry a ‘refinement that needs refining’. Current welfare issues relating to the housing and husbandry of animals used in biotelemetry studies are single vs. group housing, provision of environmental enrichment, long term laboratory housing and use of telemetered data to help assess welfare. Animals may be singly housed because more than one device transmits on the same wavelength; due to concerns regarding damage to surgical sites; because they are wearing exteriorised jackets; or if monitoring systems can only record from individually housed animals. Much of this can be overcome by thoughtful experimental design and surgery refinements. Similarly, if biotelemetry studies preclude certain enrichment items, husbandry refinement protocols can be adapted to permit some environmental stimulation. Nevertheless, long-term laboratory housing raises welfare concerns and maximum durations should be defined. Telemetered data can be used to help assess welfare, helping to determine endpoints and refine future studies. The above measures will help to improve data quality as well as welfare, because experimental confounds due to physiological and psychological stress will be minimised. PMID:26480045

  1. DIESEL PARTICLE GENERATION, CHARACTERIZATION, AND DIRECT ANIMAL EXPOSURE STUDIES

    EPA Science Inventory

    Inhalation of diesel exhaust is associated with the development of asthma as well as other adverse health effects. Studies have also demonstrated that diesel exhaust induces pulmonary changes that worsen asthmatic responses to respiratory allergens. This paper describes the des...

  2. 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 ...

  3. The impact of environmental enrichment on the outcome variability and scientific validity of laboratory animal studies.

    PubMed

    Bayne, K; Wrbel, H

    2014-04-01

    It has been widely accepted for some time that species-appropriate environmental enrichment is important for the welfare of research animals, but its impact on research data initially received little attention. This has now changed, as the use of enrichment as one element of routine husbandry has expanded. In addition to its use in the care of larger research animals, such as nonhuman primates, it is now being used to improve the environments of small research animals, such as rodents, which are used in significantly greater numbers and in a wide variety of studies. Concern has been expressed that enrichment negatively affects both experimental validity and reproducibility. However, when a concise definition of enrichment is used, with a sound understanding of the biology and behaviour of the animal as well as the research constraints, it becomes clear that the welfare of research animals can be enhanced through environmental enrichment without compromising their purpose. Indeed, it is shown that the converse is true: the provision of suitable enrichment enhances the well-being of the animal, thereby refining the animal model and improving the research data. Thus, the argument is made that both the validity and reproducibility of the research are enhanced when proper consideration is given to the research animal's living environment and the animal's opportunities to express species-typical behaviours. PMID:25000800

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

    PubMed

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

    2015-06-01

    For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals. PMID:25786332

  5. 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

    Lenartowicz, Małgorzata; Grzmil, Paweł; Shoukier, Moneef; Starzyński, Rafał; Marciniak, Marcin; Lipiński, Paweł

    2012-02-01

    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

  6. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies.

    PubMed

    Larsen, Thomas M; Toubro, Soren; Astrup, Arne

    2003-12-01

    Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health. PMID:12923219

  7. Predictive value of the efficacy of glaucoma medications in animal models: preclinical to regulatory studies.

    PubMed

    Stewart, William C; Magrath, George N; Demos, Christina M; Nelson, Lindsay A; Stewart, Jeanette A

    2011-10-01

    To gain regulatory approval for a new medicine, a pharmaceutical company must take the new product through a series of clinical trials (Phases I-III). Animal models are important in the new drug-development process because they allow for the testing of the efficacy and safety of potential new medicines in a cost-efficient manner that avoids the risk of serious adverse events to humans. Unfortunately, there is no perfect animal treatment model for glaucoma. Animal studies hopefully predict the results of clinical studies, but with estimating efficacy, the limited size and duration of these studies, as well as the animal model selection, might restrict the ability to accurately predict future results. There is little information which compares various available animal models and how well these preclinical studies predict the efficacy of a new product in clinical trials. The purpose of this review article is to analyse animal model studies evaluating potential glaucoma products and determine parameters associated with commercial availability. We discuss how animal models provide some success in predicting commercial launch of a new glaucoma medicine, especially the hypertensive and monkey models, but highlight that caution must be used in interpreting individual models or studies. PMID:21169272

  8. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    SciTech Connect

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

    1988-11-01

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 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 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. 46 refs., 6 figs., 27 tabs.

  9. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    SciTech Connect

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

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 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 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. 31 refs., 6 figs., 19 tabs.

  10. Teratological studies of prenatal exposure of mice to a 20 kHz sawtooth magnetic field.

    PubMed

    Kim, Sung-Ho; Song, Ji-Eun; Kim, Se-ra; Oh, Heon; Gimm, Youn-Myoung; Yoo, Done-Sik; Pack, Jeong-Ki; Lee, Yun-Sil

    2004-02-01

    In order to evaluate the importance of gestational age in possible effects due to exposure to a 20 kHz sawtooth magnetic field, pregnant ICR mice at gestational 2.5-15.5 days post-coitus, which is the most sensitive stage for the induction of major congenital malformations, were exposed in a carrousel irradiator. The mice were exposed to a 20 kHz intermediate frequency (IF) sawtooth magnetic field had a 6.5 microT peak intensity for 8 h/day. The animals were sacrificed on the 18th day of gestation; and the fetuses were examined for mortality, growth retardation, changes in head size, and other morphological abnormalities. From the above conditions, it is concluded that the exposure to a 20 kHz sawtooth magnetic field with 6.5 microT peak intensity does not inflict any adverse effect on fetuses of pregnant mice. PMID:14735561

  11. Immunotoxicity of zearalenone in Balb/c mice in a high subchronic dosing study counteracted by Raphanus sativus extract.

    PubMed

    Salah-Abbès, Jalila Ben; Abbès, Samir; Abdel-Wahhab, Ma; Oueslati, Ridha

    2010-12-01

    Radish (Raphanus sativus) is a cruciferous plant, rich on flavonoids, isothiocyanates, and phenolic acids. They show anti-inflammatory and immunomodulatory activity both in vitro and in vivo. Isothiocyanates and flavonoids have been reported previously to prevent low-sub-chronic dose of zearalenone (ZEN) causing immunotoxicity. The present study focuses on the amelioration of fusarotoxicosis in Balb/c mice by feeding two concentrations of radish extract. The extract at 15 and 30 mg/kg bw, was evaluated to reduce the deleterious effects in immunological parameters of high subchronic doses of 40 and 80 mg of ZEN/kg bw on modulation of lipopolysaccharide (LPS). ZEN consuming mice showed a "dose-related" decrease in weight gain and in the immune relative weights organs. Moreover, Atrophy and lymphoid depletion were seen in the histopathology of spleen. Ingestion of ZEN at either level had a significant effect on total red blood cell numbers and on their relative number of lymphocytes. Likewise, ZEN alters the production of regulatory cytokines and antibody of LPS stimulated mice. By contrast, the additions of radish extract with a low or high dose of ZEN moderately decreased the affected mice and/or the severity of lesions, and all tested parameters were normal or at least near normal levels. In addition, the radish extract alone did not produce any significant changes in all tested parameters compared with the controls. In conclusion, radish extract was effective for the protection of high dose ZEN-immunotoxication in mice and it could contribute to a solution of the ZEN immunotoxicity in humans and in farm animals. PMID:20205508

  12. Microbiological method for assaying lincomycin in animal feed: collaborative study.

    PubMed

    Neff, A W; Thomas, R W

    1978-09-01

    A microbiological assay for determining lincomycin in swine feed, supplement, and a vitamin-mineral premix was studied collaboratively in 16 laboratories. The design of the study involved a complete feed, feed supplement, and a vitamin-mineral premix covering a range of fortification from 20 to 80 g/ton and 80 to 2600 g/ton. Two methods of sample preparation were used depending on the concentration of lincomycin in the sample. Statistical evaluation of the results from the 2 methods indicated that 10 and 11 collaborators, respectively, had mean recoveries which were not significantly different from one another. Ten laboratories obtained a mean recovery of 112.2% (range 102.3--123.5%) for the lower level, and 11 laboratories obtained a mean recovery of 104.4% (range 100.0--107.7%) for the higher level. The method has been adopted as official first action. PMID:363677

  13. Plants or animals - which do junior high school students prefer to study?

    NASA Astrophysics Data System (ADS)

    Wandersee, James H.

    This research addressed the following questions: (1) Which science topic do junior high school students prefer to study - plants or animals? (2) Is their preference related to the variables of grade level and sex of student? Public school students from grades 7, 8, and 9 in Avoca, New York participated in the study. Findings show that 9th grade students have a greater interest in biological science topics than do students in the other grades studied. Girls are more interested in biological science topics than boys are. Girls also showed a significant preference for animals over plants. As a group, junior high school students revealed that they prefer animal study over plant study. About half of the student responses categorized as biological science did not express a clear-cut preference for either plants or animals. A caution about generalizability is expressed. Interviews of students suggest that the following characteristics of animals are important determinants of preferences: Animals move, eat, have eyes for sight, communicate by sound, exhibit behaviors that are fun to watch, have short and observable live cycles, interact with humans, can learn, have mates, give birth, and raise their young. It was obvious that most students think of mammals when they hear the term animal.

  14. Studies of pancreatic carcinogenesis in different animal models

    SciTech Connect

    Scarpelli, D.G.; Rao, M.S.; Reddy, J.K.

    1984-06-01

    Pancreatic carcinomas can be induced in rats, guinea pigs, and hamsters by a variety of carcinogens. The types of neoplasms which arise vary with the species of rodent. In the rat, they consist exclusively of acinar cells, in the other species the lesions are adenocarcinomas resembling those derived from pancreatic ductules and ducts, those in hamster more so than in guinea pigs. Careful sequential studies in the guinea pig and hamster suggest that acinar cells together with ductular and duct cells are involved in the genesis of duct adenocarcinomas. In each rodent model, the acinar cell appears to be quite sensitive to continued exposure to carcinogen. In each instance, acini undergo modulation, and in the guinea pig and hamster, permanent metaplastic transformation to ductlike structures. Such cells assume an enhanced capacity for cell proliferation which persists following cessation of carcinogen treatment. Other studies suggest that adult pancreatic acinar cells possess a surprising degree of plasticity. Their involvement in the pathogenesis of neoplasms resembling pancreatic ducts is not unlike other carcinogenic sequences where extensive cell modulation and metaplasia precede and are an integral part of the neoplastic transformation. 55 references, 9 figures, 4 tables.

  15. Animal models of atherosclerosis

    PubMed Central

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

    2014-01-01

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans’ stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

  16. Animal models of atherosclerosis.

    PubMed

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

    2014-05-16

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

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

    PubMed

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

    2004-01-01

    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

  18. Studies of nutritional safety of some heavy metals in mice.

    PubMed

    Hutcheson, D P; Gray, D H; Venugopal, B; Luckey, T D

    1975-06-01

    Heavy metals have been proposed as nutrient markers to allow the accurate determination of the time of passage, nutrient intake, or apparent utilization of multiple nutrients. In order to evaluate possible toxic effects of scandium, chromium, lanthanum, samarium, europium, dysprosium, terbium, thulium, and ytterbium oxides, and barium sulfate upon growth, general development, reproduction, and lactation, mice were fed different levels of these compounds for three generations. The amount of elements fed were 0,110, 100, and 1000 times the use amount. The use amounts were (in ppm2.) : Sc, 0.12; Cr, 0.02; La.0.40;; Sm. 0.80; Eu, 0.036:TB, 1.20; Dy, 1.20; Tm. 0.08; Tb, 0.12; and Ba, 0.008. The use amount was one-fifth of the concentration required for activation analysis. Mortality and morbidity were negligible. No consistent growth rate changes were observed; however, different groups showed different growth rates during different generations. The number of mice born showed no significant differences amoung treatment groups. Survival, growth rate, hematology, morphological development, maturation, reproduction, and lactational performance were comparable in mice fed the different levels of 10 heavy metal oxides to those mice fed the basal diet. PMID:1141999

  19. PERINATAL STUDY OF TOLUENE IN CD-1 MICE

    EPA Science Inventory

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

  20. A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.

    PubMed

    Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene; Lauras, Nathan; Margolskee, Robert F; Delay, Eugene R

    2012-06-01

    Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances. PMID:21987728

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

    PubMed Central

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

    1997-01-01

    Using interleukin (IL)-6-deficient (IL-6(0/0) mice or wild-type mice, we investigated the controversial role of IL-6 in joint inflammation and cartilage pathology during zymosan-induced arthritis (ZIA). Monoarticular arthritis was elicited by injection of zymosan into the right knee joint cavity. Production of IL-1, tumor necrosis factor (TNF), IL-6, and nitric oxide by the inflamed knee was assessed in washouts of joint capsule specimens. Plasma corticosterone was measured using a radioimmunoassay. Proteoglycan synthesis was assessed using [35S]sulfate incorporation into patellas ex vivo. Joint swelling was quantified by joint uptake of circulating 99mTechnetium pertechnetate. Histology was taken to evaluate cellular infiltration and cartilage damage. Zymosan caused a rapid increase in articular IL-1, IL-6, TNF, and NO levels. Except for IL-6, the released amounts and time course of these mediators were comparable in the IL-6-deficient mice and the wild-type mice. Elevated plasma corticosterone levels were measured during the first day of arthritis in both strains. At day 2 of ZIA, joint inflammation (joint swelling and cell exudate) in IL-6-deficient mice was comparable with that in the wild-type mice. The marked suppression of chondrocyte proteoglycan synthesis and proteoglycan degradation were on the average higher in the IL-6-deficient mice. Together this resulted in a more pronounced proteoglycan depletion in the IL-6-deficient mice as compared with the wild-type mice during the first week of arthritis. Injection of recombinant IL-6 into the joint cavity corrected the IL-6 deficiency and significantly reduced cartilage destruction. Inflammation was more chronic in the wild-type mice, and these mice also showed a higher prevalence for osteophyte formation. In ZIA, IL-6 plays a dual role in connective tissue pathology, reducing proteoglycan loss in the acute phase and enhancing osteophyte formation in the chronic phase. The latter could be related to the more severe joint inflammation as seen in the normal (IL-6-producing) animals during the chronic phase of arthritis. Images Figure 2 Figure 2 PMID:9212744

  2. The effect of temperature of fluorescence: an animal study

    NASA Astrophysics Data System (ADS)

    Walsh, Alex; Masters, Bart; Jansen, Duco; Welch, A. J.; Mahadevan-Jansen, Anita

    2010-02-01

    The effect of temperature on the fluorescence of enucleated porcine eyes and rat skin was studied. The fluorescence peak intensity was found to decrease as the tissue temperature increased. A dual-excitation, fiber-based system was used to collect fluorescence and diffuse-reflectance spectra from the samples. A thermal camera was used to determine the temperature of the tissue at the time of fluorescence measurement. The samples were mounted in a saline bath and measurements were made as the tissue temperature was increased from -20°C to 70°C. Results indicate that temperature affects several fluorescence spectra characteristics. The peak height decreased as temperature increased. At temperatures above 60°C, the peak position shifted to lower wavelengths. Heating and cooling experiments of the rat skin demonstrate the recovery of the loss in fluorescence. The diffuse reflectance spectra indicated a change in optical properties past 60°C, but prior to the denaturation temperature for collagen at 57°C, no change in optical properties was observed. Results suggest that the decrease in fluorescence is both a property of fluorescence and a result of altering optical properties.

  3. Skin and bone integrated prosthetic pylon: A pilot animal study

    PubMed Central

    Pitkin, Mark; Raykhtsaum, Grigory; Galibin, Oleg V.; Protasov, Mikhail V.; Chihovskaya, Julie V.; Belyaeva, Irina G.

    2016-01-01

    Direct skeletal attachment of limb prostheses is a viable alternative to traditional techniques that are based on a socket-residuum interface. Direct skeletal attachment may be a better or even the only method for patients with a very short residuum and high soft-tissue volume. The problem of integrating the prosthetic pylon with residual skin during direct skeletal attachment of a limb prosthesis has not been solved, and the use of a completely porous prosthetic pylon has not been the subject of focused, systematic research. In this in vivo study, we investigated cell (osteocyte, fibroblast, and keratinocyte) adhesion and penetration into the pores of a titanium pylon implanted in Wistar rats. The porous titanium pylon was implanted in the bone of the thigh residua of four rats. Electronic scanning and morphological analysis demonstrated integration of the pylon with the surrounding skin. These findings support the possibility of developing a natural barrier against the infection associated with direct skeletal attachment of limb prostheses. PMID:17123195

  4. Computer assisted biokinetic studies of radiopharmaceuticals in animals and humans

    SciTech Connect

    Strand, S.E.; Persson, B.R.R.; Bergqvist, L.; Joensson, P.E.; Hafstroem, L.

    1981-06-01

    A quantitative kinetic scintillation camera technique has been developed for investigation of the lymph drainage and the uptake in lymph nodes of /sup 99m/TcSb/sub 2/S/sub 3/ colloid injected subcutaneously. A model has been designed for calculating absorbed doses to injection site, lymph nodes, liver gonads and whole body based on these measurements. Sequential images were taken every 30 seconds during the first 1 to 2 hours after the injection. Static images were taken after 4 to 6 hours. The day after, lymph node dissection was performed and each specimen was measured for radioactivity and examined by light microscopy. A total of 157 lymph nodes in 9 patients were thus individually examined. The kinetics of the colloid uptake in individual nodes could be expressed by a simple two-compartment model. The outflow of colloid from the injection site was monoexponential. The volume of the injected colloid at the injection site was quantitatively studied and shown to increase with time. The average absorbed doses were calculated either with the MIRD-formalism or with a computer program designed at our institute for calculations of absorbed doses. From these calculations absorbed doses were estimated as; whole-body: 0.2 to 5.2 ..mu..Gy/MBq (0.7 to 19 mrad/mCi), gonads: 0.2 to 20 ..mu..Gy/MBq (0.7 to 70 mrad/mCi), liver: 1.4 to 3.4 ..mu..Gy/MBq (5 to 12 mrad/mCi) and lymph nodes: up to 1000 ..mu..Gy/MBq (3,700 mrad/mCi). The most probable absorbed dose to the injection site was shown to be about 15,000 ..mu..Gy/MBq (60,000 mrad/mCi).

  5. Tree shrew as a new animal model for the study of lung cancer

    PubMed Central

    YE, LIANHUA; HE, MENG; HUANG, YUNCHAO; ZHAO, GUANGQIANG; LEI, YUJIE; ZHOU, YONGCHUN; CHEN, XIAOBO

    2016-01-01

    Animal models play a key role in identifying treatments for various types of cancer, including lung cancer. The aim of the present study was to develop a new animal model for lung cancer induction using tree shrews from the Yunnan region in China. Tree shrews are suitable for a full simulation of human disease because their structure, function and metabolism are adequately close to human. This animal may offer a new experimental animal model to be used in the study of lung cancer. In the present study, 80 healthy tree shrews were distributed in experimental and control groups. Animals in the experimental group received different concentrations of iodized oil suspension of 3-methylcholanthrene (3-MC) and diethylnitrosamine (DEN) while animals in the control groups received saline or lipiodol solvent via endotracheal instillation. In the 3rd, 5th, 7th, 9th and 11th weeks the body weights of the animals were measured and chest X-ray examinations were conducted. Pathological studies on the lung tissues were also performed and the pathological changes occurring in bronchial epithelium in all the groups were examined. Animals in the experimental group gradually lost their body weight. For tree shrews in the blank control and solvent control groups the survival rates were 100 and 80%, respectively while the survival rate for the experimental group was 0%. Results from the chest X-ray conducted on animals in the blank control and solvent control groups revealed no obvious abnormalities while in the experimental group high-density shadow spots within the perfusion sites were observed. Pathological studies performed on these high-density areas confirmed changes in the bronchial epithelium. In the experimental groups we also detected bronchial epithelial atypical hyperplasia, and apparent changes in carcinoma in situ. In conclusion, lung cancer was successfully induced in tree shrews by a one-time endotracheal introduction of iodized oil suspension of 3-MC and DEN. PMID:26998127

  6. Obstructive Sleep Apnea, Oxidative Stress and Cardiovascular Disease: Lessons from Animal Studies

    PubMed Central

    Heitmann, Joerg; Seeger, Werner; Weissmann, Norbert; Schulz, Richard

    2013-01-01

    Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) diseases such as arterial hypertension, heart failure, and stroke. Based on human research, sympathetic activation, inflammation, and oxidative stress are thought to play major roles in the pathophysiology of OSA-related CV diseases. Animal models of OSA have shown that endothelial dysfunction, vascular remodelling, and systemic and pulmonary arterial hypertension as well as heart failure can develop in response to chronic intermittent hypoxia (CIH). The available animal data are clearly in favour of oxidative stress playing a key role in the development of all of these CV manifestations of OSA. Presumably, the oxidative stress is due to an activation of NADPH oxidase and other free oxygen radicals producing enzymes within the CV system as evidenced by data from knockout mice and pharmacological interventions. It is hoped that animal models of OSA-related CV disease will continue to contribute to a deeper understanding of their underlying pathophysiology and will foster the way for the development of cardioprotective treatment options other than conventional CPAP therapy. PMID:23533685

  7. Toxicology studies of a chemical mixture of 25 groundwater contaminants. III. Male reproduction study in B6C3F1 mice

    SciTech Connect

    Chapin, R.E.; Phelps, J.L.; Schwetz, B.A.; Yang, R.S. )

    1989-10-01

    A mixture of chemicals has been developed that models contaminated groundwater around hazardous waste sites. We investigated the effects of this mixture on spermatogenesis in B6C3F1 mice. The animals consumed three different concentrations of this mixture for 90 days, after which time they were euthanatized. Although there was a concentration-related decrease in the amount of fluid consumed at the higher two concentrations, there were no differences in body weight among the groups. Similarly, there was no effect of mixture consumption upon the histology of liver, kidney, testis, epididymis, or seminal vesicles or upon the absolute organ weights of these organs. Kidney weight relative to body weight was increased in the high dose group. Epididymal sperm number and testicular spermatid count were not affected by treatment. These studies show that, at exposure levels that decrease fluid intake and increase adjusted kidney weight, there were no effects of this mixture on gametogenesis in male mice.

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

    PubMed

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

    2015-04-01

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

  9. Rinderpest: a case study of animal health emergency management.

    PubMed

    Mukhopadhyay, A K; Taylor, W P; Roeder, P L

    1999-04-01

    The history of rinderpest and control of the disease in Africa and Asia is reviewed briefly. The present distribution of rinderpest virus in relation to its phylogenetic lineages is presented. Rinderpest-free countries bordering rinderpest-infected countries are considered to be under permanent threat of a transboundary rinderpest incursion and therefore face continuous and serious emergency situations. The nature of these emergencies in relation to the remaining foci of the three lineages is described. It is argued that the Global Rinderpest Eradication Programme (GREP) eradication strategies now need to focus on the use of epidemiological studies to define foci of infection and guide targeted, pulsed vaccination campaigns rather than broad, routine vaccination. The emergency posed by the re-emergence of African lineage 2 virus in East Africa and the challenge of mild rinderpest is explored in some detail as a phenomenon which may be more widespread than has been assumed. Points at which the future of GREP is threatened are illustrated and means of removing some of the dangers are suggested. The lessons which need to be learnt from the experience of the Indian National Project on Rinderpest Eradication and the Pan-African Rinderpest Campaign are discussed, including the value of strengthening surveillance systems in accordance with the Office International des Epizooties Pathway and how to cope with the problem associated with cryptic foci of rinderpest persistence--perhaps the greatest challenge facing GREP. The value of vaccine buffer zones is considered in detail and the authors conclude that unless those zones are of considerable depth and are well maintained, they are unlikely to prevent dissemination of the virus. The role of emergency preparedness planning in preventing the spread of rinderpest is discussed, with the understanding that effective surveillance, as a component of emergency preparedness planning, is safer than vaccination as a means of ensuring that the disease does not re-enter or penetrate a population. The swift initiation of a programme for the eradication of rinderpest from Pakistan is seen as the key issue in dealing with the Asian lineage rinderpest emergency. Development and implementation of strategies with the benefit of experience gained in Africa and India could provide a rapid resolution of the emergency. PMID:10190212

  10. Animal models of diabetes mellitus.

    PubMed

    Rees, D A; Alcolado, J C

    2005-04-01

    Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock-in, generalized knock-out and tissue-specific knockout mice. PMID:15787657

  11. Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice

    PubMed Central

    Mohamed, Hanan R. H.

    2016-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimer's disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer's disease incidence. PMID:27034902

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

    PubMed Central

    2012-01-01

    Background Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice’s hematocrit was about 50% lower than that of controls (p < 0.05) and their performance level was about 25% lower (p < 0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio > 1.4) and 115 were strongly down-regulated (normalized ratio < 0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail. PMID:22748015

  13. Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study.

    PubMed Central

    Dragunsky, Eugenia; Nomura, Tatsuji; Karpinski, Kazimir; Furesz, John; Wood, David J.; Pervikov, Yuri; Abe, Shinobu; Kurata, Takeshi; Vanloocke, Olivier; Karganova, Galina; Taffs, Rolf; Heath, Alan; Ivshina, Anna; Levenbook, Inessa

    2003-01-01

    OBJECTIVE: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). METHODS: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. FINDINGS: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. CONCLUSIONS: Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. PMID:12764491

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

    PubMed

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

    2013-04-01

    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

  15. Studies on the immune response of congenitally athymic (nude) mice.

    PubMed

    Jutila, J W; Reed, N D; Isaak, D D

    1975-01-01

    The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena. PMID:238688

  16. Further studies of post-partum ovulation timing in mice.

    PubMed

    Bingel, A S

    1982-07-01

    The times at which post-partum ovulation occurred relative to the times of parturition, were similar for CD-1 mice exposed either to 18L:6D of 10L:14D and comparable to the times reported previously for mice of the same strain kept under 14L:10D. When parturition took place close to 'lights off', ovulation tended to occur 13--14 h after littering (i.e. during the last part of the same dark period and the early part of the next light period). Conversely, when parturition took place closer to 'lights on', ovulation tended to be delayed by the equivalent number of hours so that it occurred during the last part of the next dark period and early part of the subsequent light period. This confirmation and extension of earlier work suggests that mice of this strain would be useful for investigating hormonal events associated with the timing of post-partum ovulation in the mouse. PMID:7201517

  17. Health Benefits of Animal Research: The Mouse in Biomedical Research.

    ERIC Educational Resources Information Center

    Jonas, Albert M.

    1984-01-01

    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,…

  18. Health Benefits of Animal Research: The Mouse in Biomedical Research.

    ERIC Educational Resources Information Center

    Jonas, Albert M.

    1984-01-01

    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,

  19. Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome.

    PubMed

    Stettner, Georg M; Viscomi, Carlo; Zeviani, Massimo; Wilichowski, Ekkehard; Dutschmann, Mathias

    2011-05-01

    Surf1 gene mutations were detected as a main cause for Leigh syndrome (LS), also known as infantile subacute necrotizing encephalomyelopathy. This syndrome which is commonly associated with systemic cytochrome c oxidase (COX) deficiency manifests in early childhood and has an invariable poor prognosis. Progressive disturbances of the respiratory function, for which both the metabolic condition and necrotizing brainstem lesions contribute, belong to the major symptoms of LS. A constitutive knockout (KO) mouse for Surf1 enables invasive investigations of distinct aspects of LS. In the present study the respiratory function was analyzed applying an arterially perfused brainstem preparation. Compared to wild type (WT) preparations Surf1 KO preparations had a higher baseline respiratory frequency and abnormal responses to hypoxia and hypercapnia that involved both respiratory frequency and motor nerve discharge pattern. These data suggest that COX deficiency impairs peripheral and/or central chemoreceptor function. PMID:21167962

  20. Eating Frequency, Food Intake, and Weight: A Systematic Review of Human and Animal Experimental Studies

    PubMed Central

    Raynor, Hollie A.; Goff, Matthew R.; Poole, Seletha A.; Chen, Guoxun

    2015-01-01

    Eating frequently during the day, or “grazing,” has been proposed to assist with managing food intake and weight. This systematic review assessed the effect of greater eating frequency (EF) on intake and anthropometrics in human and animal experimental studies. Studies were identified through the PubMed electronic database. To be included, studies needed to be conducted in controlled settings or use methods that carefully monitored food intake, and measure food intake or anthropometrics. Studies using human or animal models of disease states (i.e., conditions influencing glucose or lipid metabolism), aside from being overweight or obese, were not included. The 25 reviewed studies (15 human and 10 animal studies) contained varying study designs, EF manipulations (1–24 eating occasions per day), lengths of experimentation (230 min to 28 weeks), and sample sizes (3–56 participants/animals per condition). Studies were organized into four categories for reporting results: (1) human studies conducted in laboratory/metabolic ward settings; (2) human studies conducted in field settings; (3) animal studies with experimental periods <1 month; and (4) animal studies with experimental periods >1 month. Out of the 13 studies reporting on consumption, 8 (61.5%) found no significant effect of EF. Seventeen studies reported on anthropometrics, with 11 studies (64.7%) finding no significant effect of EF. Future, adequately powered, studies should examine if other factors (i.e., disease states, physical activity, energy balance and weight status, long-term increased EF) influence the relationship between increased EF and intake and/or anthropometrics. PMID:26734613

  1. Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis.

    PubMed

    Bush, Ronald A; Wei, Lisa L; Sieving, Paul A

    2015-08-01

    Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

  2. Ethics and animal welfare evaluations in South East Asian zoos: a case study of Thailand.

    PubMed

    Agoramoorthy, Govindasamy; Harrison, Bernard

    2002-01-01

    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 welfare evaluations are conducted in South East Asian zoos. The study identified several major and minor welfare problems and provided constructive suggestions to zoo authorities, which in turn significantly improved the standards of animal welfare. Thus, the data presented in this article could serve as a model for other zoos to follow animal welfare evaluations locally, regionally, and globally. PMID:12738585

  3. Approaches to the study of traditional behaviors of free-living animals.

    PubMed

    Galef, Bennett G

    2004-02-01

    I review literature on four different approaches to the study of traditions in animals: observation of free-living animals, laboratory experiment, armchair analysis, and field experiment. Because, by definition, a tradition entails social learning of some kind, it is difficult, perhaps impossible, to establish that a behavior is in fact traditional without knowledge of how it develops. Observations of free-living animals often provide strong circumstantial evidence of a tradition. However, even in the view of several researchers who have studied possibly traditional behaviors in natural populations, observation alone has not proven sufficient to show that social learning contributes to development of behaviors of interest. The relevance of laboratory experiments to the understanding of the development of behaviors in free-living animals is always open to challenge. Armchair analyses of field data can produce interesting hypotheses but cannot test them. Field experiments to determine how behaviors of interest develop in population members provide a promising way forward. PMID:15161140

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

    PubMed Central

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

    2014-01-01

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

  5. Toxicology and carcinogenesis studies of diethylphthalate (Cas No. 84-66-2) in F344/n rats and B6C3F1 mice (dermal studies) with dermal initiation/promotion study of diethylphthalate and dimethylphthalate (Cas No. 131-11-3) in male Swiss (CD-1 (trade name)) mice. Technical report

    SciTech Connect

    1995-05-01

    Toxicology and carcinogenicity studies were conducted by dermal administration of diethylphthalate to groups of 60 F344/N rats of each sex at doses of 0, 100, or 300 microL and to groups of 60 B6C3F1 mice of each sex at doses of 0, 7.5, 15, or 30 microL. Neat chemical was applied to rats for 5 days per week for 103 weeks and up to 10 animals per group were evaluated after 15 months. Mice received doses in 100 microL of acetone for 5 days per weeks for 103 weeks with a 1 week recovery period, and up to 10 animals per group were evaluated after 15 months. Under the conditions of these 2-year dermal studies, there was not evidence of carcinogenic activity of diethylphthalate in male or female F344/N rats receiving 100 or 300 microL. There was equivocal evidence of carcinogenic activity of diethylphthalate in male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms, primarily adenomas. In the initiation/promotion model, there was no evidence of initiating or promoting activity of diethylphthalate or dimethylphthalate in male Swiss (CD-1) mice.

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

    SciTech Connect

    HABER, S.B.

    1987-06-26

    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.

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

    SciTech Connect

    Wagner, Hans-Joachim; Stinner, Benno; Barth, Peter; Klose, Klaus-Jochen

    2000-07-15

    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.

  8. Retaining vets in farm animal practice: a cross-sectional study.

    PubMed

    Adam, K; Baillie, S; Rushton, J

    2015-06-20

    Concerns have been raised about a potential shortage of farm animal vets in the UK. There is no apparent lack of new graduates willing to work with farm animals, but practices report difficulties in recruiting and retaining experienced farm animal vets. Retention of vets in farm animal practice has been identified as a key issue for the sustainability of veterinary businesses and livestock health. A cross-sectional study design was used to identify factors associated with vets remaining in farm animal practice. Data were collected via an online questionnaire covering employment, education, personal background and future plans. The target population was vets with experience of farm animal work in the UK. 380 responses were included in the analysis. Working in a practice where accommodation was provided and an increasing number of years since graduation were associated with significantly lower odds of remaining in farm animal practice, while working in a practice where staff appraisals were carried out; coming from a family with a commercial farm; spending more time on farm work and being on call with an experienced vet in the first job after graduation increased the odds of remaining in farm work. Gender was not significantly associated with retention. PMID:26002092

  9. An animal model of congestive (dilated) cardiomyopathy: dilatation and hypertrophy of the heart in the chronic stage in DBA/2 mice with myocarditis caused by encephalomyocarditis virus.

    PubMed

    Matsumori, A; Kawai, C

    1982-08-01

    To investigate whether lesions that develop in the chronic stage of viral myocarditis are similar to those seen in congestive (dilated) cardiomyopathy, we studied myocarditis in inbred strains of DBA/2 mice infected with encephalomyocarditis (EMC) virus. Myocardial necrosis with calcification appeared on day 4. Thereafter, myocardial necrosis became more extensive and mononuclear cell infiltration was evident and was most marked on day 14. On day 90, cellular infiltration had decreased and myocardial fibrosis was prominent. At this stage, the heart weight was significantly greater in the infected mice than in the controls (0.190 +/- 0.028 g vs 0.122 +/- 0.013 g, mean +/- SD) (p less than 0.001) and the cavity dimensions of the left ventricle were larger (1.67 +/- 0.29 mm vs 1.11 +/- 0.20 mm) (p less than 0.001). The diameters of myocardial fibers of the right ventricle, the interventricular septum and the left ventricle were significantly larger than those of the controls (right ventricle, 16.6 +/- 1.8 vs 13.4 +/- 1.5 micrometer; interventricular septum, 17.8 +/- 1.5 vs 13.8 +/- 1.5 micrometer; left ventricle, 19.4 +/- 1.7 vs 14.8 +/- 1.1 micrometer) (p less than 0.001). This study demonstrates that in viral myocarditis in the chronic stage, lesions develop that resemble those seen in congestive cardiomyopathy. PMID:6212162

  10. Using Bayesian analysis in repeated preclinical in vivo studies for a more effective use of animals.

    PubMed

    Walley, Rosalind; Sherington, John; Rastrick, Joe; Detrait, Eric; Hanon, Etienne; Watt, Gillian

    2016-05-01

    Whilst innovative Bayesian approaches are increasingly used in clinical studies, in the preclinical area Bayesian methods appear to be rarely used in the reporting of pharmacology data. This is particularly surprising in the context of regularly repeated in vivo studies where there is a considerable amount of data from historical control groups, which has potential value. This paper describes our experience with introducing Bayesian analysis for such studies using a Bayesian meta-analytic predictive approach. This leads naturally either to an informative prior for a control group as part of a full Bayesian analysis of the next study or using a predictive distribution to replace a control group entirely. We use quality control charts to illustrate study-to-study variation to the scientists and describe informative priors in terms of their approximate effective numbers of animals. We describe two case studies of animal models: the lipopolysaccharide-induced cytokine release model used in inflammation and the novel object recognition model used to screen cognitive enhancers, both of which show the advantage of a Bayesian approach over the standard frequentist analysis. We conclude that using Bayesian methods in stable repeated in vivo studies can result in a more effective use of animals, either by reducing the total number of animals used or by increasing the precision of key treatment differences. This will lead to clearer results and supports the "3Rs initiative" to Refine, Reduce and Replace animals in research. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27028721

  11. Predictive Criteria to Study the Pathogenesis of Malaria-Associated ALI/ARDS in Mice

    PubMed Central

    Ortolan, Luana S.; Sercundes, Michelle K.; Debone, Daniela; Hagen, Stefano C. F.; D' Império Lima, Maria Regina; Alvarez, José M.; Marinho, Claudio R. F.; Epiphanio, Sabrina

    2014-01-01

    Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS) often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described; we still lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP) were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability, and serum vascular endothelial growth factor (VEGF) levels according to either the day of death or the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration) and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease. PMID:25276057

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. 26-Week dermal oncogenicity study evaluating pure trans-capsaicin in Tg.AC hemizygous mice (FBV/N).

    PubMed

    Chanda, Sanjay; Erexson, Gregory; Frost, Denzil; Babbar, Sunita; Burlew, Jo-Anne; Bley, Keith

    2007-01-01

    The objective of this study was to assess the oncogenic potential of trans-capsaicin when administered weekly via topical application to the dorsal skin of Tg.AC mice for 26 weeks. Male and female Tg.AC mice (25 mice/sex/group) received dose formulations containing trans-capsaicin dissolved in diethylene glycol monoethyl ether (DGME). The positive control was tetradecanoylphorbol-13-acetate (TPA) dissolved in DGME. Appropriate controls, including a topical lidocaine local anesthetic pretreatment (4%w/w), were maintained. All groups were dosed once weekly, except for the TPA group, which was dosed twice per week. Analysis of the macroscopic observations after the final sacrifice revealed no noteworthy treatment-related findings, with the exception of dermal masses that were randomly dispersed throughout all treatment groups for both males and females. The frequency of dermal masses in the capsaicin-treated groups (at a dose level of up to 102 mg/kg and an application rate of 25.6 mg/cm2/kg/week) was not elevated in comparison to either concurrent vehicle or untreated controls. In contrast, a notable increase in the frequency of dermal masses was observed in the TPA-treated mice compared to both the concurrent vehicle and untreated controls. Dermal application of capsaicin resulted in no increased incidence of preneoplastic or neoplastic skin lesions. In contrast, over half the male and female mice exposed to TPA had multiple skin papillomas; the majority of the TPA-treated animals either died early or was humanely euthanized due to tumor load. Spontaneously occurring neoplasms were not appreciably increased in capsaicin-treated animals. Capsaicin-related non-neoplastic microscopic findings were seen sporadically in both genders and included acanthosis, hyperkeratosis/parakeratosis (primarily females), epidermal crusts, subepidermal fibrosis, epidermal ulcerations/erosions, and chronic-active inflammation. There was no evidence of a dose response in either the incidence or severity of these findings. The lidocaine- (at a dose level of 162 mg/kg and at an application rate of 40.5 mg/cm2/kg/week) and DGME-treated (at a dose level of 4.0 g/kg and at an application rate of 1 g/cm2/kg/week) control groups also did not display any evidence of increase in dermal masses. Based on these results, trans-capsaicin, lidocaine, and DGME should be considered nononcogenic in the Tg.AC mouse dermal model. PMID:17454252

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

    PubMed

    Andrini, Laura B; García, Marcela N; Inda, Ana María; Errecalde, Ana Lía

    2013-11-01

    Partial hepatectomy (PH) alters serum concentrations of substances involved in cellular proliferation, leading to the compensatory liver hyperplasia. Furthermore, angiogenesis is mainly stimulated by vascular endothelial growth factor (VEGF) and is a fundamental requirement either in liver regeneration or in tumours growth. This study looks at the expression of VEGF, DNA synthesis (DNAs) and mitotic activity (MA) in hepatectomised (H) and hepatectomised-tumour bearing (HTB) mice throughout a 24 h period. Adult male mice were sacrificed every 4 h from 26 to 50 h post-hepatectomy. H mice show a circadian rhythm in VEGF expression with a maximum value of 2.6 ± 0.1 at 08/46 h of day/hours posthepatectomy (HD/HPH); in DNAs, the maximum value was 3.4 ± 0.3 at 16/30 (HD/HPH) and in MA it was 2.3 ± 0.01 at 12/50 (HD/HPH). In HTB animals the peak of VEGF expression appears at 16/30 (HD/HPH) with a maximum value of 3.7 ± 0.1, the peak of DNAs was at 00/38 (HD/HPH) with a value of 4.6 ± 0.3 and the maximum value of MA of 08/46 (HD/HPH) with a value of 3.01 ± 0.3. We can conclude that the presence of the tumour induces modifications in the intensity and the temporal distribution of the circadian curves of VEGF expression, DNAs and MA of hepatectomised animals. PMID:23881839

  16. Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research

    PubMed Central

    Mignini, Luciano E; Khan, Khalid S

    2006-01-01

    Background Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. Methods We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996–2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. Results Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. Conclusion There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research. PMID:16533396

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

    PubMed

    Depauw, S; Bosch, G; Hesta, M; Whitehouse-Tedd, K; Hendriks, W H; Kaandorp, J; Janssens, G P J

    2012-08-01

    The natural diet of felids contains highly digestible animal tissues but also fractions resistant to small intestinal digestion, which enter the large intestine where they may be fermented by the resident microbial population. Little information exists on the microbial degradability of animal tissues in the large intestine of felids consuming a natural diet. This study aimed to rank animal substrates in their microbial degradability by means of an in vitro study using captive cheetahs fed a strict carnivorous diet as fecal donors. Fresh cheetah fecal samples were collected, pooled, and incubated with various raw animal substrates (chicken cartilage, collagen, glucosamine-chondroitin, glucosamine, rabbit bone, rabbit hair, and rabbit skin; 4 replicates per substrate) for cumulative gas production measurement in a batch culture technique. Negative (cellulose) and positive (casein and fructo-oligosaccharides; FOS) controls were incorporated in the study. Additionally, after 72 h of incubation, short-chain fatty acids (SCFA), including branched-chain fatty acids (BCFA), and ammonia concentrations were determined for each substrate. Glucosamine and glucosamine-chondroitin yielded the greatest organic matter cumulative gas volume (OMCV) among animal substrates (P < 0.05), whereas total SCFA production was greatest for collagen (P < 0.05). Collagen induced an acetate production comparable with FOS and a markedly high acetate-to-propionate ratio (8.41:1) compared with all other substrates (1.67:1 to 2.97:1). Chicken cartilage was rapidly fermentable, indicated by a greater maximal rate of gas production (R(max)) compared with all other substrates (P < 0.05). In general, animal substrates showed an earlier occurrence for maximal gas production rate compared with FOS. Rabbit hair, skin, and bone were poorly fermentable substrates, indicated by the least amount of OMCV and total SCFA among animal substrates (P < 0.05). The greatest amount of ammonia production among animal substrates was measured after incubation of collagen and rabbit bone (P < 0.05). This study provides the first insight into the potential of animal tissues to influence large intestinal fermentation in a strict carnivore, and indicates that animal tissues have potentially similar functions as soluble or insoluble plant fibers in vitro. Further research is warranted to assess the impact of fermentation of each type of animal tissue on gastro-intestinal function and health in the cheetah and other felid species. PMID:22287677

  18. Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

    SciTech Connect

    Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

    1989-02-01

    Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.

  19. Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies.

    PubMed

    Niwa, Ohtsura

    2003-10-13

    Many studies confirmed that radiation induces genomic instability in whole-body systems. However, the results of the studies are not always consistent with each other. Attempts are made in the present review to resolve the discrepancies. Many of the studies in human and experimental animals utilize the length change mutation of minisatellite sequences as a marker of genomic instability. Minisatellite sequences frequently change their length, and the data obtained by conventional Southern blotting give rather qualitative information, which is sometimes difficult to scrutinize quantitatively. This is the problem inevitably associated with the study of minisatellite mutations and the source of some conflicts among studies in humans and mice. Radiation induction of genomic instability has also been assessed in whole-body experimental systems, using other markers such as the mouse pink-eyed unstable allele and the specific pigmentation loci of medaka fish (Oryzias latipes). Even though there are some contradictions, all these studies have demonstrated that genomic instability is induced in the germ cells of irradiated parents, especially of males, and in offspring born to them. Among these, transmission of genomic instability to the second generation of irradiated parents is limited to the mouse minisatellite system, and awaits further clarification in other experimental systems. PMID:14557813

  20. An ultrastructural study of neuromuscular spindles in normal mice: with reference to mice and man infected with Mycobacterium leprae.

    PubMed Central

    Edwards, R P

    1975-01-01

    Mycobacterium leprae have been found within muscle spindles in mice, using electron microscopy, and in man, using light microscopy. Their mode of entry clearly is important. It may be via capsular cells, capillaries or nerves. For this reason muscle spindles from normal mice were studied by electron microscopy with special reference to the capsule and the relationship of it with capillaries and nerves, as well as details of the intrafusal fibres and capsular space. A fenestrated capillary was found between the capsular cell layers and outside the capsule in one spindle and in another spindle both a fenestrated and a continuous type of a capillary were found between the capsular cells; this may be of interest for pharmacological studies. However, the muscle spindles of the mouse were in the main similar to muscle spindles studied by other workers in man and other mammals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Figs. 8-11 PMID:126981

  1. Experimental animal model to study iron overload and iron chelation and review of other such models.

    PubMed

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2015-10-01

    The disorders of iron overload due to primary or secondary cause are one of the important human diseases leading to high mortality if untreated. To understand this, an animal model has been extensively studied. The source of iron administered to the mode of iron administration that can mimic the iron overload in humans has been studied. A safe and orally active iron chelator is still needed as many of the existing compounds have different types of complications and toxicity associated. Hence having a simple animal model which can be availed quickly and can be used to study various compounds for its iron chelating activity would likely to have immense utility for pharmacological studies. In this review we have shown how, using a simple procedure, a large number of small iron overloaded animals can be produced easily for various studies. PMID:26227843

  2. Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

    PubMed

    Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan

    2014-07-01

    Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats. PMID:24713262

  3. Critical Analysis of Assessment Studies of the Animal Ethics Review Process †

    PubMed Central

    Varga, Orsolya

    2013-01-01

    Simple Summary In many countries, the approval of animal research projects depends on the decisions of the ethics committees which review the projects. Since the efficiency of the protection of experimental animals greatly depends on the performance of the ethics committees, its regular assessment is crucial. This paper reviews the results of studies assessing the performance of the ethics committees, and emphasizes the importance of outcome assessment in the evaluation of the performance of ethics committees. Abstract In many countries the approval of animal research projects depends on the decisions of Animal Ethics Committees (AEC’s), which review the projects. An animal ethics review is performed as part of the authorization process and therefore performed routinely, but comprehensive information about how well the review system works is not available. This paper reviews studies that assess the performance of animal ethics committees by using Donabedian’s structure-process-outcome model. The paper points out that it is well recognised that AECs differ in structure, in their decision-making methods, in the time they take to review proposals and that they also make inconsistent decisions. On the other hand, we know little about the quality of outcomes, and to what extent decisions have been incorporated into daily scientific activity, and we know almost nothing about how well AECs work from the animal protection point of view. In order to emphasise this viewpoint in the assessment of AECs, the paper provides an example of measures for outcome assessment. The animal suffering is considered as a potential measure for outcome assessment of the ethics review. Although this approach has limitations, outcome assessment would significantly increase our understanding of the performance of AECs. PMID:26479540

  4. Toxicity studies with 5-hydroxymethylfurfural and its metabolite 5-sulphooxymethylfurfural in wild-type mice and transgenic mice expressing human sulphotransferases 1A1 and 1A2.

    PubMed

    Bauer-Marinovic, Morana; Taugner, Felicitas; Florian, Simone; Glatt, Hansruedi

    2012-05-01

    5-Sulphooxymethylfurfural (SMF), an electrophilic metabolite of the abundant Maillard product 5-hydroxymethylfurfural (HMF), was intraperitoneally administered to FVB/N mice. At a dosage of 250 mg/kg, most animals died after 5-11 days due to massive damage to proximal tubules. At lower dosages, administered repeatedly, tubules also were the major target of toxicity, with regeneration and atypical hyperplasia occurring at later periods. Additionally, hepatotoxic effects and serositis of peritoneal tissues were observed. SMF is a minor metabolite of HMF in conventional mice, but HMF is an excellent substrate for a major sulphotransferase (hSULT1A1) in humans. Parental FVB/N mice and FVB/N-hSULT1A1/2 mice, carrying multiple copies of the hSULT1A1/2 gene cluster, were exposed to HMF in drinking water (0, 134 and 536 mg/kg body mass/day) for 12 weeks. Nephrotoxic effects and enhanced proliferation of hepatocytes were only detected at the high dosage. They were mild and, surprisingly, unaffected by hSULT1A1/2 expression. Thus, SMF was a potent nephrotoxicant when administered as a bolus, but did not reach levels sufficient to produce serious toxicity when generated from HMF administered continuously via drinking water. This was even the case in transgenic mice expressing clearly higher HMF sulphation activity in liver and kidney than humans. PMID:22349055

  5. Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis

    PubMed Central

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

    2013-01-01

    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. PMID:22142960

  6. Pathogenesis of experimental rabies in mice: an immunohistochemical study.

    PubMed

    Jackson, A C; Reimer, D L

    1989-01-01

    The spread of rabies virus in the central nervous system of mice was examined after hindlimb footpad and intracerebral inoculation of the CVS strain of fixed rabies virus. All mice developed paralytic rabies. After intracerebral inoculation there was early simultaneous infection of neurons in the cerebral cortex and pyramidal neurons of the hippocampus, and later there was spread to the cerebellum. After high-dose intracerebral inoculation there was early infection in ependymal cells lining the lateral ventricles and neurons adjacent to the central canal of the spinal cord, suggesting that rabies virus entry into the CNS occurs, at least in part, by a cerebrospinal fluid pathway. The sequence of involvement was different after hindlimb footpad inoculation. Infection became established in the cerebellum on day 5, in the cerebral cortex on day 6, and in the hippocampus on day 8. CA3 was initially affected, CA1 became infected 2 days later, and there was much less involvement of the dentate gyrus. Hippocampal infection occurred late relative to the rest of the brain after peripheral inoculation, but not after intracerebral inoculation. The hippocampus is not a good location for the detection of early brain infection after peripheral inoculation, although it may be involved when a natural rabies vector has the ability to transmit infection. These findings also raise questions about the mechanisms for the limbic dysfunction observed in clinical rabies. PMID:2750485

  7. Animal Diseases and Your Health

    MedlinePlus

    ... well. Though they may be cute and cuddly, wild animals may carry germs, viruses, and parasites. Deer and ... mice carry ticks that cause Lyme disease. Some wild animals may carry rabies. Enjoy wildlife from a distance. ...

  8. EXPERIMENTAL ANIMAL MAINTENANCE

    DOEpatents

    Finkel, M.P.

    1962-01-22

    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)

  9. Potential for using a hermetically-sealed, positive-pressured isocage system for studies involving germ-free mice outside a flexible-film isolator.

    PubMed

    Paik, Jisun; Pershutkina, Olesya; Meeker, Stacey; Yi, Jaehun J; Dowling, Susan; Hsu, Charlie; Hajjar, Adeline M; Maggio-Price, Lillian; Beck, David A C

    2015-07-01

    Germ-free mice are used to examine questions about the role of the gut microbiota in development of diseases. Generally these animals are maintained in semi-rigid or flexible-film isolators to ensure their continued sterility or, if colonized with specific microbiota, to ensure that no new species are introduced. Here, we describe the use of a caging system in which individual cages are hermetically sealed and have their own filtered positive airflow. This isopositive caging system requires less space and reduces animal housing costs. By using strict sterile techniques, we kept mice germ-free in this caging system for 12 weeks. We also used this caging system and approach to conduct studies evaluating a) the stability of the microbiome in germ-free mice receiving a fecal transplant and b) the stability of dietary-induced microbiota changes in fecal-transplanted mice. As has been shown in fecal transfer studies in isolators, we found that the transferred microbiota stabilizes as early as 2 weeks post transfer although recipient microbiota did not completely recapitulate those of the donors. Interestingly, we also noted some sex effects in these studies indicating that the sex of recipients or donors may play a role in colonization of microbiota. However, a larger study will be needed to determine what role, if any, sex plays in colonization of microbiota. Based on our studies, an isopositive caging system may be utilized to test multiple donor samples for their effects on phenotypes of mice in both normal and disease states even with limited available space for housing. PMID:26177210

  10. NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1986-04-01

    Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic profiles were performed at 3-month intervals. These studies were designed and conducted because of large production volume and potential human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining potential carcinogenicity in laboratory animals. In the 2-year studies, mean body weights of the 200 mg/kg male rats (-23%) and the 100 mg/kg mice (-14% to -19%) were lower than those of the vehicle controls, and survival of dosed groups decreased with increasing dose (rats--male: vehicle control, 32/50; low dose, 29/50; mid dose, 25/50; high dose, 16/50; female: 46/50; 38/50; 34/50; 25/50; mice--male: 28/50; 23/50; 18/50; 7/50; female: 30/50; 26/50; 24/50; 18/50). At week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Significantly increased (P<0.05) incidences of neoplasms were observed at multiple sites for male and female rats and for male and female mice. Primary neoplasms observed in rats and mice are summarized in Table 1 (see page 12 of the Technical Report). Hematologic data from vehicle control and dosed rats and mice were obtained at 3-month intervals from 0 to 24 months. Reliably identifiable hematologic effects were limited to lymphocytopenia and associated leukocytopenia in benzene-dosed rats and mice. These effects were seen from 3 to 18 months in dosed male rats and in dosed male mice; a similar but less pronounced response was observed in dosed female rats during this same time period. The effect in female mice was limited to 12-18 months. The technical quality of certain of these data was questionable; thus, more detailed analyses (e.g., investig questionable; thus, more detailed analyses (e.g., investigation of the association between hematologic and pathologic changes) are deemed inappropriate for these data. Benzene increased the frequency of micronucleated normchromatic peripheral erythrocytes in male and female mice (rats were not examined); males were more sensitive than females. The hematopoietic system of rats and mice of each sex was affected by benzene in the 2-year studies. The incidences of malignant lymphomas in all dosed groups of mice were greater than those in the vehicle controls (male: 4/49; 9/48; 9/50; 15/49; female: 15/49; 24/45; 24/50; 20/49). Lymphoid depletion of the splenic follicles (rats) and thymus (male rats) was observed at increased incidences. Bone marrow hematopoietic hyperplasia was observed at increased incidences in dosed mice of each sex (male: 0/49; 11/48; 10/50; 25/49; female: 3/49; 14/45; 8/50; 13/49). The incidences of Zymbal gland carcinomas in mid and high dose male rats and in dosed female rats were greater than those in the vehicle controls (male: 2/32; 6/46; 10/42; 17/42; female: 0/45; 5/40; 5/44; 14/46). The incidences of Zymbal gland carcinomas in mid and high dose male mice and in high dose female mice were greater than those in the vehicle controls (male: 0/43; 1/34; 4/40; 21/39; female: 0/43; 0/32; 1/37; 3/31). In mid and high dose male mice and in high dose female mice, the incidences of epithelial hyperplasia of the Zymbal gland were also increased (male: 0/43; 3/34; 12/40; 10/39; female: 1/43; 1/32; 2/37; 6/31). Hyperplasia of the adrenal capsule was observed at increased incidences in dosed mice of each sex (male: 2/47; 32/48; 14/49; 4/46; female: 5/49; 19/44; 34/50; 30/48). The incidence of pheochromocytomas in mid dose male mice was greater than that in the vehicle controls (male: 1/47; 1/48; 7/49; 1/46), whereas the incidences in dosed female mice were lower than that in the vehicle controls (female: 6/49; 1/44; 1/50; 1/48). Hyperplasia of the zona fasciculata of the adrenal cortex was observed at increased incidences in low dose rats of each sex (male: 0/50; 13/49; 0/48; 2/49; female: 0/50; 17/50; 0/47; 0/49). Benzene was associated with increased incidences of neoplasms of the skin and oral cavity of rats. The incidences of squamous cell papillomas and squamous cell carcinomas of the skin in high dose male rats were greater than those in the vehicle controls (squamous cell papilloma: 0/50; 2/50; 1/50; 5/50; squamous cell carcinoma: 0/50; 5/50; 3/50; 8/50). Increased incidences of uncommon squamous cell papillomas or squamous cell carcinomas (combined) of the oral cavity were observed in dosed male and female rats (male: 1/50; 9/50; 16/50; 19/50; female: 1/50; 5/50; 12/50; 9/50). Incidences of squamous cell papillomas or carcinomas (combined) (male: 2/45; 2/42; 3/44; 5/38; female: 1/42; 3/40; 6/45; 5/42), hyperkeratosis, and epithelial hyperplasia of the forestomach were increased in some dosed groups of male and female mice; incidences of hyperkeratosis and acanthosis were increased in high dose male rats. Compound-related effects in the lung, harderian gland, preputial gland, ovary, mammary gland, and liver were seen in mice but not in rats. Administration of benzene was associated with increased incidences of alveolar epithelial hyperplasia in mid and high dose mice (male: 2/49; 3/48; 7/50; 10/49; female: 1/49; 1/42; 9/50; 6/49). Increased incidences of alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined) were observed in high dose male mice (carcinomas: 5/49; 11/48; 12/50; 14/49; adenomas or carcinomas: 10/49; 16/48; 19/50; 21/49). Alveolar/bronchiolar adenomas were seen at increased incidences in high dose female mice (4/49; 2/42; 5/50; 9/49), as were alveolar/bronchiolar carcinomas (0/49; 3/42; 6/50; 6/49) and alveolar/bronchiolar adenomas or carcinomas combined (4/49; 5/42; 10/50; 13/49) in mid and high dose female mice. The incidences of focal or diffuse hyperplasia of the harderian gland were increased in dosed mice of each sex (male: 0/49; 5/46; 11/49; 7/48; female: 6/48; 10/44; 11/50; 10/47). The incidences of harderian gland adenomas (0/49; 9/46; 13/49; 11/48) in dosed male mice were greater than that in the vehicle controls. A marginal increase in the incidence of adenomas or carcinomas (combined) of the harderian gland was seen in high dose female mice (5/48; 6/44; 10/50; 10/47). The administration of benzene to male mice was associated with increased incidences of hyperplasia (1/21; 18/28; 9/29; 1/35) and squamous cell carcinomas (0/21; 3/28; 18/29; 28/35) of the preputial gland. Increased incidences of mammary gland carcinomas were found in mid dose and high dose female mice (0/49; 2/45; 5/50; 10/49) and carcinosarcomas in high dose female mice (0/49; 0/45; 1/50; 4/49). Increased incidences of various uncommon neoplastic and nonneoplastic lesions of the ovary (papillary cystadenoma, luteoma, granulosa cell tumor, tubular adenoma, benign mixed tumor, epithelial hyperplasia, and senile atrophy) were associated with the administration of benzene to female mice. In mid and high dose female mice, the incidences of granulosa cell tumors (1/47; 1/44; 6/49; 7/48) and benign mixed tumors (0/47; 1/44; 12/49; 7/48) were greater than those in the vehicle controls. Increased incidences of hepatocellular adenomas were observed in low dose female mice (1/49; 8/44; 5/50; 4/49) and hepatocellular adenomas or carcinomas (combined) in low dose and mid dose female mice (4/49; 12/44; 13/50; 7/49). An audit of the experimental data was conducted for these 2-year carcinogenesis studies on benzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice, and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F1 mice. Synonyms: benzol, cyclohexatriene, pyrobenzol PMID:12748714

  11. Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases

    PubMed Central

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

    2013-01-01

    Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10−9). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature. PMID:23874156

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

    NASA Astrophysics Data System (ADS)

    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

    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.

  13. On the Use of a Simple Physical System Analogy to Study Robustness Features in Animal Sciences

    PubMed Central

    Sadoul, Bastien; Martin, Olivier; Prunet, Patrick; Friggens, Nicolas C.

    2015-01-01

    Environmental perturbations can affect the health, welfare, and fitness of animals. Being able to characterize and phenotype adaptive capacity is therefore of growing scientific concern in animal ecology and in animal production sciences. Terms borrowed from physics are commonly used to describe adaptive responses of animals facing an environmental perturbation, but no quantitative characterization of these responses has been made. Modeling the dynamic responses to an acute challenge was used in this study to facilitate the characterization of adaptive capacity and therefore robustness. A simple model based on a spring and damper was developed to simulate the dynamic responses of animals facing an acute challenge. The parameters characterizing the spring and the damper can be interpreted in terms of stiffness and resistance to the change of the system. The model was tested on physiological and behavioral responses of rainbow trout facing an acute confinement challenge. The model has proven to properly fit the different responses measured in this study and to quantitatively describe the different temporal patterns for each statistical individual in the study. It provides therefore a new way to explicitly describe, analyze and compare responses of individuals facing an acute perturbation. This study suggests that such physical models may be usefully applied to characterize robustness in many other biological systems. PMID:26322508

  14. Critical Analysis of Assessment Studies of the Animal Ethics Review Process.

    PubMed

    Varga, Orsolya

    2013-01-01

    In many countries the approval of animal research projects depends on the decisions of Animal Ethics Committees (AEC's), which review the projects. An animal ethics review is performed as part of the authorization process and therefore performed routinely, but comprehensive information about how well the review system works is not available. This paper reviews studies that assess the performance of animal ethics committees by using Donabedian's structure-process-outcome model. The paper points out that it is well recognised that AECs differ in structure, in their decision-making methods, in the time they take to review proposals and that they also make inconsistent decisions. On the other hand, we know little about the quality of outcomes, and to what extent decisions have been incorporated into daily scientific activity, and we know almost nothing about how well AECs work from the animal protection point of view. In order to emphasise this viewpoint in the assessment of AECs, the paper provides an example of measures for outcome assessment. The animal suffering is considered as a potential measure for outcome assessment of the ethics review. Although this approach has limitations, outcome assessment would significantly increase our understanding of the performance of AECs. PMID:26479540

  15. Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.

    PubMed

    Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl

    2008-11-01

    Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. PMID:19025323

  16. Animal cytomegaloviruses.

    PubMed Central

    Staczek, J

    1990-01-01

    Cytomegaloviruses are agents that infect a variety of animals. Human cytomegalovirus is associated with infections that may be inapparent or may result in severe body malformation. More recently, human cytomegalovirus infections have been recognized as causing severe complications in immunosuppressed individuals. In other animals, cytomegaloviruses are often associated with infections having relatively mild sequelae. Many of these sequelae parallel symptoms associated with human cytomegalovirus infections. Recent advances in biotechnology have permitted the study of many of the animal cytomegaloviruses in vitro. Consequently, animal cytomegaloviruses can be used as model systems for studying the pathogenesis, immunobiology, and molecular biology of cytomegalovirus-host and cytomegalovirus-cell interactions. PMID:2170830

  17. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

    PubMed

    Spengler, Jessica R; Bergeron, Éric; Rollin, Pierre E

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology. PMID:26741652

  18. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

    PubMed Central

    Spengler, Jessica R.; Bergeron, Éric; Rollin, Pierre E.

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology. PMID:26741652

  19. Determination of ulixertinib in mice plasma by LC-MS/MS and its application to a pharmacokinetic study in mice.

    PubMed

    Kumar, Rajinish; Suresh, P S; Rudresh, G; Zainuddin, Mohd; Dewang, Purushottam; Kethiri, Ragahava Reddy; Rajagopal, Sriram; Mullangi, Ramesh

    2016-06-01

    A sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of ulixertinib in mice plasma using phenacetin as an internal standard (I.S.) as per regulatory guidelines. Sample preparation was accomplished through a protein precipitation procedure with acetonitrile:methanol mixture. Chromatographic separation was performed on Atlantis dC18 column using a binary gradient using mobile phase A (0.2% formic acid in water) and B (acetonitrile) at a flow rate of 0.60mL/min. Elution of ulixertinib and I.S. occurred at ∼1.07 and 1.20min, respectively. The total chromatographic run time was 2.5min. A linear response function was established in the concentration range of 1.58-2054ng/mL. The intra- and inter-day accuracy and precisions were in the range of 2.11-11.8 and 5.80-11.4%, respectively. This novel method has been applied to a pharmacokinetic study in mice. PMID:27017572

  20. An experimental study of the "faster-is-slower" effect using mice under panic

    NASA Astrophysics Data System (ADS)

    Lin, Peng; Ma, Jian; Liu, Tianyang; Ran, Tong; Si, Youliang; Li, Tao

    2016-06-01

    A number of crowd accidents in last decades have attracted the interests of scientists in the study of self-organized behavior of crowd under extreme conditions. The faster-is-slower effect is one of the most referenced behaviors in pedestrian dynamics. However, this behavior has not been experimentally verified yet. A series of experiments with mice under panic were conducted in a bi-dimensional space. The mice were trained to be familiar with the way of escape. A varying number of joss sticks were used to produce different levels of stimulus to drive the mice to escape. The evacuation process was video-recorded for further analysis. The experiment found that the escape times significantly increased with the levels of stimulus due to the stronger competition of selfish mice in panic condition. The faster-is-slower effect was experimentally verified. The probability distributions of time intervals showed a power law and the burst sizes exhibited an exponential behavior.

  1. Carcinogenicity study of cochineal in B6C3F1 mice.

    PubMed

    Mori, H; Iwata, H; Tanaka, T; Morishita, Y; Mori, Y; Kojima, T; Okumura, A

    1991-09-01

    The carcinogenicity of cochineal, a red colouring used in food and other products, was studied in a 2-yr bioassay in B6C3F1 mice. Groups of 50-55 mice of each sex were given 0, 3 or 6% cochineal in the diet for 2 yr. Mice of all groups developed tumours including hepatocellular adenomas or carcinomas, pulmonary adenomas or adenocarcinomas and lymphomas or lymphatic leukaemias, and the incidences of these tumours were not significantly different in treated and control groups. The results indicate that cochineal lacks carcinogenicity in mice and are consistent with those of in vitro short-term assays of cochineal and of carminic acid, an active principle of cochineal. PMID:1937288

  2. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Approval based on evidence of effectiveness from studies in animals. 601.91 Section 601.91 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible §...

  3. 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...

  4. Post-Operative Benefits of Animal-Assisted Therapy in Pediatric Surgery: A Randomised Study

    PubMed Central

    Calcaterra, Valeria; Veggiotti, Pierangelo; Palestrini, Clara; De Giorgis, Valentina; Raschetti, Roberto; Tumminelli, Massimiliano; Mencherini, Simonetta; Papotti, Francesca; Klersy, Catherine; Albertini, Riccardo; Ostuni, Selene; Pelizzo, Gloria

    2015-01-01

    Background Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period. Patients and Methods Forty children (3–17 years) were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underwent a 20 min session with an animal-assisted therapy dog, after surgery) or the standard-group (n = 20, standard postoperative care). The study variables were determined in each patient, independently of the assigned group, by a researcher unblinded to the patient’s group. The outcomes of the study were to define the neurological, cardiovascular and endocrinological impact of animal-assisted therapy in response to stress and pain. Electroencephalogram activity, heart rate, blood pressure, oxygen saturation, cerebral prefrontal oxygenation, salivary cortisol levels and the faces pain scale were considered as outcome measures. Results After entrance of the dog faster electroencephalogram diffuse beta-activity (> 14 Hz) was reported in all children of the animal-assisted therapy group; in the standard-group no beta-activity was recorded (100% vs 0%, p<0.001). During observation, some differences in the time profile between groups were observed for heart rate (test for interaction p = 0.018), oxygen saturation (test for interaction p = 0.06) and cerebral oxygenation (test for interaction p = 0.09). Systolic and diastolic blood pressure were influenced by animal-assisted therapy, though a higher variability in diastolic pressure was observed. Salivary cortisol levels did not show different behaviours over time between groups (p=0.70). Lower pain perception was noted in the animal-assisted group in comparison with the standard-group (p = 0.01). Conclusion Animal-assisted therapy facilitated rapid recovery in vigilance and activity after anaesthesia, modified pain perception and induced emotional prefrontal responses. An adaptative cardiovascular response was also present. Trial Registration ClinicalTrials.gov NCT02284100 PMID:26039494

  5. Refining Housing, Husbandry and Care for Animals Used in Studies Involving Biotelemetry.

    PubMed

    Hawkins, Penny

    2014-01-01

    Biotelemetry can contribute towards reducing animal numbers and suffering in disciplines including physiology, pharmacology and behavioural research. However, the technique can also cause harm to animals, making biotelemetry a 'refinement that needs refining'. Current welfare issues relating to the housing and husbandry of animals used in biotelemetry studies are single vs. group housing, provision of environmental enrichment, long term laboratory housing and use of telemetered data to help assess welfare. Animals may be singly housed because more than one device transmits on the same wavelength; due to concerns regarding damage to surgical sites; because they are wearing exteriorised jackets; or if monitoring systems can only record from individually housed animals. Much of this can be overcome by thoughtful experimental design and surgery refinements. Similarly, if biotelemetry studies preclude certain enrichment items, husbandry refinement protocols can be adapted to permit some environmental stimulation. Nevertheless, long-term laboratory housing raises welfare concerns and maximum durations should be defined. Telemetered data can be used to help assess welfare, helping to determine endpoints and refine future studies. The above measures will help to improve data quality as well as welfare, because experimental confounds due to physiological and psychological stress will be minimised. PMID:26480045

  6. Practical method for radioactivity distribution analysis in small-animal PET cancer studies.

    PubMed

    Slavine, Nikolai V; Antich, Peter P

    2008-12-01

    We present a practical method for radioactivity distribution analysis in small-animal tumors and organs using positron emission tomography imaging with a calibrated source of known activity and size in the field of view. We reconstruct the imaged mouse together with a source under the same conditions, using an iterative method, Maximum likelihood expectation-maximization with system modeling, capable of delivering high-resolution images. Corrections for the ratios of geometrical efficiencies, radioisotope decay in time and photon attenuation are included in the algorithm. We demonstrate reconstruction results for the amount of radioactivity within the scanned mouse in a sample study of osteolytic and osteoblastic bone metastasis from prostate cancer xenografts. Data acquisition was performed on the small-animal PET system, which was tested with different radioactive sources, phantoms and animals to achieve high sensitivity and spatial resolution. Our method uses high-resolution images to determine the volume of organ or tumor and the amount of their radioactivity has the possibility of saving time, effort and the necessity to sacrifice animals. This method has utility for prognosis and quantitative analysis in small-animal cancer studies, and will enhance the assessment of characteristics of tumor growth, identifying metastases, and potentially determining the effectiveness of cancer treatment. The possible application for this technique could be useful for the organ radioactivity dosimetry studies. PMID:18667322

  7. Comparative study of American cutaneous leishmaniasis and diffuse cutaneous leishmaniasis in two strains of inbred mice.

    PubMed Central

    Pérez, H; Arredondo, B; González, M

    1978-01-01

    Two Leishmania strains, AZV (isolated from a typical case of American cutaneous leishmaniasis) and AMP (from a case of diffuse cutaneous leishmaniasis), were studied in C57BL/6 and BALB/c mice. After infection with 10(4) amastigotes of either strain, C57BL/6 mice developed self-resolving lesions lasting 20 to 23 weeks and showed both delayed hypersensitivity response to leishmanial antigen and specific agglutinating antibodies. On the other hand, BALB/c mice infected with 10(4) AZV or AMP amastigotes developed chronic, large, ulcerated lesions and showed impaired cellular and humoral responses to the parasite. When BALB/c and C57BL/6 mice received 10(2) AMP amastigotes, patterns of infection were similar to those observed after inoculation of 10(4) amastigotes. In vitro studies revealed that spleen cells from AZV- or AMP-infected C57BL/6 mice showed an increased DNA-synthetic response to leishmanial antigen, concanavalin A, and phytohemagglutinin. Spleen cells from AZV- or AMP-infected BALB/c mice showed an increased response to concanavalin A and diminished responses to leishmanial antigen, phytohemagglutinin, and lipopolysaccharide. PMID:730354

  8. Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice.

    PubMed

    Mutlu, Oguz; Gumuslu, Esen; Kokturk, Sibel; Ulak, Guner; Akar, Furuzan; Erden, Faruk; Kaya, Havva; Tanyeri, Pelin

    2016-02-01

    Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration. PMID:26791996

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

    PubMed Central

    Kalmar, Isabelle; Vanrompay, Daisy

    2013-01-01

    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

  10. Animal studies of neonatal hypothermic neuroprotection have translated well in to practice.

    PubMed

    Gunn, Alistair J; Thoresen, Marianne

    2015-12-01

    The discovery that mild, induced hypothermia can improve neurological recovery after global moderate to severe hypoxia-ischemia has been a dramatic validation of the strong foundation of preclinical studies that informed current protocols. The major challenge is to find ways to further improve outcomes. As discussed in this review, the findings from large clinical trials of extended cooling are highly concordant with recent animal studies. These findings support the use of precise, carefully selected animal models to refine our strategies to protect babies with moderate to severe encephalopathy before instigating further large trials. PMID:25930163

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Xue, Chunyan; Rosen, Richard; Jordan, Adrienne; Hu, Dan-Ning

    2015-01-01

    Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons) against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases. PMID:26617995

  14. Overview of Vertebrate Animal Models of Fungal Infection

    PubMed Central

    Hohl, Tobias M.

    2014-01-01

    Fungi represent emerging infectious threats to human populations worldwide. Mice and other laboratory animals have proved invaluable in modeling clinical syndromes associated with superficial and life-threatening invasive mycoses. This review outlines salient features of common vertebrate animal model systems to study fungal pathogenesis, host antifungal immune responses, and antifungal compounds. PMID:24709390

  15. The elevated T-maze task as an animal model to simultaneously investigate the effects of drugs on long-term memory and anxiety in mice.

    PubMed

    Asth, Laila; Lobão-Soares, Bruno; André, Eunice; Soares, Vanessa de Paula; Gavioli, Elaine Cristina

    2012-04-10

    The elevated T-maze (ETM) is an apparatus derived from the elevated plus-maze test, which is used to evaluate anxiety. Because anxiety is a biasing factor in models of memory, this study proposed the ETM as a task for the simultaneous assessment of memory and anxiety in mice. The ETM consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. The anxiolytic diazepam (DZP; 1 or 2mg/kg) and the amnestic biperiden (BPR; 0.5, 1 or 3mg/kg) were injected at three distinct times: pre-training, post-training, and pre-test. Pre-training administration of BPR 1 and DZP 2 increased the number of trials needed to reach the avoidance criterion, suggesting a passive avoidance learning impairment. However, BPR induced hyperlocomotion, which could bias the interpretation of any BPR-induced effects during the training session. Pre-training injection of BPR did not affect the spontaneous increase in the latency to enter an open arm between trials, while DZP reduced latencies in the first three trials suggesting anxiolysis. In the test session, pre-training injection of BPR 1 and DZP 2 reduced latencies to enter an open arm, indicating memory impairment. Post-training and pre-test injection of DZP or BPR did not affect memory. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs. PMID:22394406

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

    PubMed Central

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

    2013-01-01

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

  17. Col6a1 Null Mice as a Model to Study Skin Phenotypes in Patients with Collagen VI Related Myopathies: Expression of Classical and Novel Collagen VI Variants during Wound Healing

    PubMed Central

    Lettmann, Sandra; Bloch, Wilhelm; Maaß, Tobias; Niehoff, Anja; Schulz, Jan-Niklas; Eckes, Beate; Eming, Sabine A.; Bonaldo, Paolo; Paulsson, Mats; Wagener, Raimund

    2014-01-01

    Patients suffering from collagen VI related myopathies caused by mutations in COL6A1, COL6A2 and COL6A3 often also display skin abnormalities, like formation of keloids or “cigarette paper” scars, dry skin, striae rubrae and keratosis pilaris (follicular keratosis). Here we evaluated if Col6a1 null mice, an established animal model for the muscle changes in collagen VI related myopathies, are also suitable for the study of mechanisms leading to the skin pathology. We performed a comprehensive study of the expression of all six collagen VI chains in unwounded and challenged skin of wild type and Col6a1 null mice. Expression of collagen VI chains is regulated in both skin wounds and bleomycin-induced fibrosis and the collagen VI α3 chain is proteolytically processed in both wild type and Col6a1 null mice. Interestingly, we detected a decreased tensile strength of the skin and an altered collagen fibril and basement membrane architecture in Col6a1 null mice, the latter being features that are also found in collagen VI myopathy patients. Although Col6a1 null mice do not display an overt wound healing defect, these mice are a relevant animal model to study the skin pathology in collagen VI related disease. PMID:25158062

  18. Seroprevalence studies on animal chlamydiosis amongst ruminants in five states of India

    PubMed Central

    Chahota, R.; Gupta, S.; Bhardwaj, B.; Malik, P.; Verma, S.; Sharma, and M.

    2015-01-01

    Background and Aim: Animal chlamydiosis, caused by different chlamydial species, is characterized by clinical or subclinical disease manifestations in cattle, buffalo, ovine, caprine and wild animal species. Animal chlamydiosis often remains underdiagnosed or undiagnosed, and its status in many parts of India is still unknown. Hence, the present study was conducted to determine the seroprevalence of animal chlamydiosis amongst ruminant livestock species of five states of India. Materials and Methods: Totally, 2127 randomly selected serum samples collected from ruminant livestock species viz. cattle (n=430), buffaloes (n=429), sheep (906) and goats (n=362), were tested by agar gel precipitation test for chlamydiosis between 2002 and 2011. Precipitating antigen was prepared from locally isolated strain of Chlamydia psittaci after treatment with sodium deoxycholate. Results: The chlamydial seroprevalence detected amongst ruminants in five states of India was: Himachal Pradesh: Cattle-10.90%, sheep-10.60% and goats- 22.46%; Punjab: Cattle-1.45%; Andhra Pradesh: Cattle-2.80%, buffaloes-0.93%, sheep-8.90% and goats-9.46%; Maharashtra: goats-8.33%; Jammu and Kashmir: sheep-12.50%. The mean seroprevalence values of each animal species are: Cattle-4.65%, buffaloes-0.93%, sheep-9.82% and goats-19.33%. Conclusion: The results indicate the endemic nature of animal chlamydiosis across five states in India. Hence, it requires further extensive studies in other parts of India also using chlamydial species-specific diagnostics to ascertain overall countrywide prevalence of the disease. The zoonotic nature of the chlamydiae of ruminant origin further adds significance to such prevalence studies.

  19. Genomic Methylation Inhibits Expression of Hepatitis B Virus Envelope Protein in Transgenic Mice: A Non-Infectious Mouse Model to Study Silencing of HBV Surface Antigen Genes

    PubMed Central

    Graumann, Franziska; Churin, Yuri; Tschuschner, Annette; Reifenberg, Kurt; Glebe, Dieter; Roderfeld, Martin; Roeb, Elke

    2015-01-01

    Objective The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methylation of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface protein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice. Methods Liver and serum of HBs transgenic mice aged 5–33 weeks were analyzed by Western blot, immunohistochemistry, serum analysis, PCR, and qRT-PCR. Results From the third month of age hepatic loss of HBs was observed in 20% of transgenic mice. The size of HBs-free area and the relative number of animals with these effects increased with age and struck about 55% of animals aged 33 weeks. Loss of HBs-expression was strongly correlated with amelioration of serum parameters ALT and AST. In addition lower HBs-expression went on with decreased ER-stress. The loss of surface protein expression started on transcriptional level and appeared to be regulated epigenetically by DNA methylation. The amount of the HBs-expression correlated negatively with methylation of HBV DNA in the mouse genome. Conclusions Our data suggest that methylation of specific CpG sites controls gene expression even in HBs-transgenic mice with truncated HBV genome. More important, the loss of HBs expression and intracellular aggregation ameliorated cell stress and liver integrity. Thus, targeted modulation of HBs expression may offer new therapeutic approaches. Furthermore, HBs-transgenic mice depict a non-infectious mouse model to study one possible mechanism of HBs gene silencing by hypermethylation. PMID:26717563

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

    PubMed

    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

    2010-11-01

    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(ΔM51). 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

  1. NTP Toxicology and Carcinogenesis Studies of Tetranitromethane (CAS No. 509-14-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    PubMed

    1990-03-01

    Tetranitromethane is a volatile contaminant formed during the manufacture of TNT and has been used as a rocket fuel and biochemical reagent. Toxicology and carcinogenesis studies were conducted in F344/N rats and B6C3F1 mice of each sex by whole body exposure to tetranitromethane vapor (greater than 99% pure), 6 hours per day, 5 days per week for 14 days, 13 weeks, or 2 years. Additional groups of male mice were exposed to tetranitromethane for evaluation at 1 year. Genetic toxicology studies were performed in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day Studies: Exposure concentrations ranged from 2 to 25 ppm for rats and from 2 to 50 ppm for mice. All rats exposed to 25 ppm and all mice exposed at the top concentration of 50 ppm died by day 2; reduced survival was seen in mice exposed to 25 ppm and in rats exposed to 10 ppm. Pulmonary edema in rats and inflammation of the lung in mice were seen in those animals in the 25- and 50-ppm exposure groups examined microscopically. Thirteen-Week Studies: Exposure concentrations ranged from 0.2 to 10 ppm for rats and mice. No exposure-related deaths occurred in rats. The final mean body weight of rats exposed to 10 ppm was 16% lower than that of controls for males and 6% lower for females. Exposure-related histologic effects included squamous metaplasia of the respiratory epithelium of the nasal mucosa and chronic inflammation of the lung. No deaths of mice could be clearly related to exposure to tetranitromethane. The final mean body weights of mice exposed to 5 or 10 ppm were 5% or 12% lower than that of controls for males and 9% or 12% lower for females. Exposure-related histologic effects in mice included inflammation and squamous metaplasia of the respiratory epithelium of the nasal mucosa and hyperplasia of the bronchiolar epithelium. Based on the incidences and severity of lesions in the respiratory at the higher concentrations used in the 13-week studies, exposure concentrations chosen for the 2-year studies were 0, 2, and 5 ppm for groups of 50 rats of each sex and 0, 0.5, and 2 ppm for groups of 50 mice of each sex. Additional groups of 6 or 10 male mice were exposed at concentrations of 0, 0.5, or 2 ppm for 1 year. Body Weights and Survival in the Two-Year Studies: Mean body weights of male and female rats exposed to 5 ppm were approximately 5%-15% lower than those of controls after week 70. Survival of rats at 104 weeks was as follows: male: control, 18/50; 2 ppm, 17/50; 5 ppm, 4/50; female: 25/50; 34/50; 15/50; survival of rats at the top concentration was reduced due to neoplasia. Mean body weights of exposed mice were variable and ranged as much as 10% below those of controls during the second year of the studies. Survival of exposed male mice at 104 weeks was significantly lower than that of controls due to neoplasia (control, 37/50; 0.5 ppm, 26/50; 2 ppm, 15/50). Survival of female mice was not significantly affected by exposure to tetranitromethane (31/50; 28/50; 24/50). Neoplastic and Nonneoplastic Effects in the Two-Year Studies: Effects of exposure to tetranitromethane were limited to the respiratory tract. Hyperplasia of the alveolar and bronchiolar epithelium was observed at increased incidences in exposed rats. The incidence of alveolar/bronchiolar adenomas and carcinomas were markedly increased in exposed male and female rats, with carcinomas (many of which metastasized to other sites) occurring in nearly all rats exposed to the top concentration of 5 ppm (adenomas or carcinomas-- male: control, 1/50; 2 ppm, 33/50; 5 ppm, 46/50; female: 0/50; 22/50; 50/50). Many of the rats exposed to 5 ppm also had squamous cell carcinomas of the lung (male: 0/50; 1/50; 19/50; female: 0/50; 1/50; 12/50). Hyperplasia of the respiratory epithelium and chronic inflammation of the nasal mucosa were observed at increased incidences in exposed male and female rats. Squamous metaplasia of the respiratory epithelium was increased in exposed male rats. No neoplasms of the nasal passage were seen. In exposed mice, hyperplasia of the alveolar and br were seen. In exposed mice, hyperplasia of the alveolar and bronchiolar epithelium was observed at increased incidences. Alveolar/bronchiolar neoplasms, primarily carcinomas (many of which metastasized to other sites), were increased in exposed male and female mice (male: control, 12/50; 0.5 ppm, 27/50; 2 ppm, 47/50; female: 4/49; 24/50; 49/50). Chronic inflammation of the nasal mucosa and hyperplasia and squamous metaplasia of the respiratory epithelium of the nasal cavity occurred at increased incidences in female mice exposed to 2 ppm. No primary neoplasms of the nasal passage were observed in mice. Oncogene Analysis: DNA from 14/19 rat and 4/4 mouse lung neoplasms caused morphologic transformation after transfection into cultured NIH/3T3 fibroblasts. The transforming gene from both rat and mouse lung neoplasms was determined by Southern blot analysis to be an activated K-ras oncogene. Further studies showed a GC-->AT transition in the second base of the 12th codon of the K-ras oncogene. Genetic Toxicology: Tetranitromethane was mutagenic in S. typhimurium strains TA98, TA100, and TA1535 with and without exogenous metabolic activation (S9); no mutagenic activity was observed in TA1537 with or without S9. Chromosomal aberrations were observed in CHO cells treated in vitro with tetranitromethane in the presence of S9. Sister chromatid exchanges were induced in CHO cells in the absence of S9. Conclusions: Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic activity of tetranitromethane for male and female F344/N rats and male and female B6C3F1 mice, based on increased incidences of alveolar/bronchiolar neoplasms in both species and squamous cell carcinomas of the lung in rats. Chronic inflammation of the nasal mucosa was related to exposure in rats and female mice, and hyperplasia and squamous metaplasia of the respiratory epithelium were increased in exposed male rats. Synonym: TNM PMID:12637973

  2. The auditory cortex and tinnitus – a review of animal and human studies.

    PubMed

    Eggermont, Jos J

    2015-03-01

    Tinnitus is the sound heard in the absence of physical sound sources external or internal to the body. Tinnitus never occurs in isolation; it typically develops after hearing loss, and not infrequently for losses at the higher frequencies not tested in clinical audiology. Furthermore, tinnitus is often accompanied by hyperacusis, i.e. increased loudness sensitivity, which may reflect the central gain change in the auditory system that occurs after hearing loss. I will first review the electrophysiological findings in the thalamus and cortex pertaining to animal research into tinnitus. This will comprise the changes in tonotopic maps, spontaneous firing rates and changes in pairwise neural cross-correlation induced by tinnitus-inducing agents that are commonly used in animal experiments. These are systemic application of sodium salicylate, and noise exposure at levels ranging from those that do not cause a hearing loss, to those that only cause a temporary threshold shift, to those that cause a permanent hearing loss. Following this, I will review neuroimaging and electrophysiological findings in the auditory cortex in humans with tinnitus. The neural substrates of tinnitus derived from animal data do not apply universally, as neither hearing loss nor hyperacusis appear to be necessary conditions for tinnitus to occur in humans. Finally, I will relate the findings in humans to the predictions from animal models of tinnitus. These comparisons indicate that neural correlates of tinnitus can be studied successfully both at the level of animal models and in humans. PMID:25728183

  3. [Small animal image-guided radiotherapy: A new era for preclinical studies].

    PubMed

    Delpon, G; Frelin-Labalme, A-M; Heinrich, S; Beaudouin, V; Noblet, C; Begue, M; Le Deroff, C; Pouzoulet, F; Chiavassa, S

    2016-02-01

    Preclinical external beam radiotherapy irradiations used to be delivered with a static broad beam. To promote the transfer from animal to man, the preclinical treatment techniques dedicated to the animal have been optimized to be similar to those delivered to patients in clinical practice. In this context, preclinical irradiators have been developed. Due to the small sizes of the animals, and the irradiation beams, the scaling to the small animal dimensions involves specific problems. Reducing the size and energy of the irradiation beams require very high technical performance, especially for the mechanical stability of the irradiator and the spatial resolution of the imaging system. In addition, the determination of the reference absorbed dose rate must be conducted with a specific methodology and suitable detectors. To date, three systems are used for preclinical studies in France. The aim of this article is to present these new irradiators dedicated to small animals from a physicist point of view, including the commissioning and the quality control. PMID:26856635

  4. Diagnosing and monitoring of invasive aspergillosis during antifungal therapy by polymerase chain reaction: an experimental study in mice.

    PubMed

    Lass-Flörl, Cornelia; Speth, Cornelia; Mayr, Astrid; Würzner, Reinhard; Dierich, Manfred P; Ulmer, Hanno; Dietrich, Hermann

    2003-12-01

    This study evaluated the value of polymerase chain reaction (PCR) for diagnosing and monitoring of invasive aspergillosis during amphotericin B therapy. PCR, microscopy and culture of tissues samples (n = 126) and blood samples (n = 78) of experimentally infected mice (n = 42) were performed. The PCR results of treated were compared to those of untreated animals; Aspergillus fumigatus and A. terreus were used in this study. In the amphotericin B treated group the sensitivities of PCR, microscopic examination and culture of the various tissues were 69, 58, and 53%, respectively; the specificities of all examinations were 100%. In the untreated group the sensitivities of PCR, microscopic examination, and culture were 72, 64, and 57%, respectively; the specificities of all examinations were 100%. The 78 blood samples taken from mice under therapy were tested by PCR over a period of 8 days following Aspergillus infection. The test sensitivity was 77%, the specificity 46%, the positive predictive value 59%, and the negative predictive value 67%. In the untreated group the sensitivity was 92%, the specificity 46%, the positive predictive value 63%, and the negative predictive value 86%. The results suggest that this PCR method has possible clinical value for improving the diagnosis of invasive Aspergillus infection. Monitoring of blood under antifungal therapy is not recommended. PMID:14711477

  5. Immunological studies on mice exposed subacutely to methyl isocyanate

    SciTech Connect

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

    1987-06-01

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

  6. Histological evaluation of pure NOTES - related complications in a survival animal study.

    PubMed

    Pătraşcu, St; Surlin, V; Râmboiu, S; Georgescu, E

    2011-01-01

    Considered as an extension of both laparoscopic surgery and interventional endoscopy, natural orifice transluminal endoscopic surgery (NOTES) is emerging as a new alternative of minimal invasive surgery. Literature on the gastrointestinal complications of this novel technique is sparse. The goal of this study was the histopathologic evaluation of postoperative complications in a NOTES experimental animal group. Ten female pigs (Sus scrofus domesticus) underwent transgastric endoscopic oophorectomy and tubectomy followed by gastric closure using OTSC clips. Fourteen days after surgery, the animals were sacrificed. Based on the gross examination during necropsy focused excisional biopsies were performed. Gross and microscopic evidence of gastric ulcer distal to the puncture site and perigastric lymph node abscess were found on one animal. Histological evaluation plays a determinant role in the correct evaluation of postoperative complications of pure NOTES procedures. PMID:21892532

  7. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota.

    PubMed

    Smith, Karen; McCoy, Kathy D; Macpherson, Andrew J

    2007-04-01

    Vertebrates are essentially born germ-free but normally acquire a complex intestinal microbiota soon after birth. Most of these organisms are non-pathogenic to immunocompetent hosts; in fact, many are beneficial, supplying vitamins for host nutrition and filling the available microbiological niche to limit access and consequent pathology when pathogens are encountered. Thus, mammalian health depends on mutualism between host and flora. This is evident in inflammatory conditions such as inflammatory bowel disease, where aberrant responses to microbiota can result in host pathology. Studies with axenic (germ-free) or deliberately colonised animals have revealed that commensal organisms are required for the development of a fully functional immune system and affect many physiological processes within the host. Here, we describe the technical requirements for raising and maintaining axenic and gnotobiotic animals, and highlight the extreme diversity of changes within and beyond the immune system that occur when a germ-free animal is colonized with commensal bacteria. PMID:17118672

  8. The Relationship between Domestic Violence and Animal Abuse: An Australian Study

    ERIC Educational Resources Information Center

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

    2008-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    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

    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 fo