Science.gov

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. [Heavy water (D20) inhibits growth of human xenotransplanted oropharyngeal cancers. An animal experiment study in nude mice].

    PubMed

    Altermatt, H J; Gebbers, J O; Arnold, W; Laissue, J A

    1987-04-01

    The large mass ratio of D to H, 2 to 1, gives rise to multiple effects in living organisms, when D is administered as heavy water (D2O). Deuterium at high concentration interferes with cell division and depresses the uptake of DNA-precursors in mammalian cells (Katz et al., 1970). However, the effects of D2O on the organism disappear after cessation of deuteration of the body water. Mammals do not survive more than 35% of D2O substitution for normal water in their body fluids for long periods of time. However, mice drinking 30% D2O have a normal life span and normal body weight (Katz et al., 1970; Hodel et al., 1982). Heavy water also exerts antineoplastic effects. We demonstrated that moderate body deuteration combined with a cytostatic drug significantly increases the survival time of mice bearing transplantable murine neoplasms (Laissue et al., 1982). Hitherto, it is not known whether heavy water affects human neoplasms in the same way. Therefore, we have studied human squamous cell carcinomas of the oropharyngeal region which were xenografted in nude mice. A moderate deuteration of body water of the mice (less than or equal to 20 atom %) drinking 30% D2O, inhibited the tumour growth markedly by a factor of 0.4 to 0.5 compared to the growth of the same tumours in control animals drinking tap water. This effect of D2O seems to be directly proportional to the grade of malignancy of the carcinomas. Histologically, no differences were detectable between the original carcinomas and the tumour grafts in animals with and without D2O. PMID:3037213

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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.

  15. Shank mutant mice as an animal model of autism

    PubMed Central

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

    2014-01-01

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

  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. Studies of retroviral infection in humanized mice.

    PubMed

    Marsden, Matthew D; Zack, Jerome A

    2015-05-01

    Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research. PMID:25680625

  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 PGF2?, 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. Arsenite cocarcinogenesis: an animal model derived from genetic toxicology studies.

    PubMed Central

    Rossman, Toby G; Uddin, Ahmed N; Burns, Fredric J; Bosland, Maarten C

    2002-01-01

    Although epidemiologic evidence shows an association between inorganic arsenic in drinking water and increased risk of skin, lung, and bladder cancers, no animal model for arsenic carcinogenesis has been successful. This lack has hindered mechanistic studies of arsenic carcinogenesis. Previously, we and others found that low concentrations (< or =5 microm) of arsenite (the likely environmental carcinogen), which are not mutagenic, can enhance the mutagenicity of other agents, including ultraviolet radiation (UVR) and alkylating agents. This enhancing effect appears to result from inhibition of DNA repair by arsenite, but not via inhibition of DNA repair enzymes. Rather, low concentrations of arsenite disrupt p53 function and upregulate cyclin D1. Failure to find an animal model for arsenic carcinogenesis might be because arsenite is not a carcinogen per se but acts as an enhancing agent (cocarcinogen) with a genotoxic partner. We tested this hypothesis with solar UVR in hairless but immunocompetent Skh1 mice. Mice were given 10 mg/L sodium arsenite in drinking water (or not) and irradiated with 1.7 KJ/m(2) solar UVR 3 times weekly. As expected, no tumors appeared in any organs in control mice or in mice given arsenite alone. After 26 weeks irradiated mice given arsenite had a 2.4-fold increase in skin tumor yield compared with mice given UVR alone. The tumors were mostly squamous cell carcinomas, and those occurring in mice given UVR plus arsenite were much larger and more invasive. These results are consistent with the hypothesis that arsenic acts as a cocarcinogen with a second (genotoxic) agent by inhibiting DNA repair and/or enhancing positive growth signaling. Skin cancers in populations drinking water containing arsenic may be caused by the enhancement by arsenic compounds of carcinogenesis induced by UVR (or other environmental agents). It is possible that lung and bladder cancers associated with arsenic in drinking water may also require a carcinogenic partner. PMID:12426125

  4. 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.

  5. 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.

  6. Video database system for studying animal behavior

    NASA Astrophysics Data System (ADS)

    Jiang, Haitao; Dailey, Jeffery W.

    1996-11-01

    Classification of farm animal behaviors are based upon oral or written descriptions of the activity that an animal is engaged in. The quantification of animal behavior for research requires that an individual recognize and code the behavior of the animal under study. The classification of these behaviors can be subjective and may differ among observers. Illustrated guides to animal behavior do not convey the motion associated with most behaviors. Video based guides offer a subjective method of quantifying behaviors with real time demonstrations of the components that make up a behavior. In this paper, we propose an animal behavior video database system which can automatically extract animal motion information from the input animal activity video clip by a multi-object tracking and reasoning system. The extracted information is then analyzed and described using a set of standard animal behavior terms we are developing. The behavior description is used to automatically annotate the given video clip, and serves as the content-based index. The user of the system is able to use a keywork description of the behavior to retrieve the corresponding video object. The intended applications of the system are animal and veterinary science education, and animal behavior research. The prototype system is built for swine and will be extended to other farm animal species.

  7. 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

  8. 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...

  9. 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.

  10. The effects of group and single housing and automated animal monitoring on urinary corticosterone levels in male C57BL/6 mice.

    PubMed

    Kamakura, Remi; Kovalainen, Miia; Leppluoto, Juhani; Herzig, Karl-Heinz; Mkel, Kari A

    2016-02-01

    Mice are used extensively in physiological research. Automated home-cage systems have been developed to study single-housed animals. Increased stress by different housing conditions might affect greatly the results when investigating metabolic responses. Urinary corticosteroid concentration is considered as a stress marker. The aim of the study was to compare the effects of different housing conditions and an automated home-cage system with indirect calorimetry located in an environmental chamber on corticosterone levels in mice. Male mice were housed in different conditions and in automated home-cage system to evaluate the effects of housing and measuring conditions on urine corticosterone levels. Corticosterone levels in single-housed mice in the laboratory animal center were consistently lower compared with the group-housed mice. Single-housed mice in a separate, small animal unit showed a rise in their corticosterone levels a day after they were separated to their individual cages, which decreased during the following 2days. The corticosterone levels of group-housed mice in the same unit were increased during the first 7days and then decreased. On day 7, the corticosterone concentrations of group-housed mice were significantly higher compared with that of single-housed mice, including the metabolic measurement protocol. In conclusion, single housing caused less stress when compared with group-housed mice. In addition, the urine corticosterone levels were decreased in single-housed mice before the metabolic measurement started. Thus, stress does not affect the results when utilizing the automated system for measuring metabolic parameters like food and water intake and calorimetry. PMID:26869685

  11. 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.

  12. 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.

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

    PubMed Central

    Kobezda, Tams; Ghassemi-Nejad, Sheida; Mikecz, Katalin; Glant, Tibor T.; Szekanecz, Zoltn

    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

  14. 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

  15. 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)-?, interferon (IFN)-?, 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-?, IFN-?, 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-?, IFN-?, and IL-2 play an important role in the process of TCE sensitization. PMID:26111540

  16. 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.

  17. 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

  18. 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

  19. Neutral aminoaciduria in cystathionine ?-synthase-deficient mice; an animal model of homocystinuria.

    PubMed

    Akahoshi, Noriyuki; Kamata, Shotaro; Kubota, Masashi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Yamazaki, Chiho; Yoshida, Yuka; Yamada, Hidenori; Ishizaki, Yasuki; Suematsu, Makoto; Kasahara, Tadashi; Ishii, Isao

    2014-06-15

    The kidney is one of the major loci for the expression of cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CTH). While CBS-deficient (Cbs(-/-)) mice display homocysteinemia/methioninemia and severe growth retardation, and rarely survive beyond the first 4 wk, CTH-deficient (Cth(-/-)) mice show homocysteinemia/cystathioninemia but develop with no apparent abnormality. This study examined renal amino acid reabsorption in those mice. Although both 2-wk-old Cbs(-/-) and Cth(-/-) mice had normal renal architecture, their serum/urinary amino acid profiles largely differed from wild-type mice. The most striking feature was marked accumulation of Met and cystathionine in serum/urine/kidney samples of Cbs(-/-) and Cth(-/-) mice, respectively. Levels of some neutral amino acids (Val, Leu, Ile, and Tyr) that were not elevated in Cbs(-/-) serum were highly elevated in Cbs(-/-) urine, and urinary excretion of other neutral amino acids (except Met) was much higher than expected from their serum levels, demonstrating neutral aminoaciduria in Cbs(-/-) (not Cth(-/-)) mice. Because the bulk of neutral amino acids is absorbed via a B(0)AT1 transporter and Met has the highest substrate affinity for B(0)AT1 than other neutral amino acids, hypermethioninemia may cause hyperexcretion of neutral amino acids. PMID:24761004

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

    PubMed

    Hunfeld, Anika; Segelcke, Daniel; Bcker, Ingo; Mecheri, Badreddine; Hemmer, Kathrin; Dlugosch, Elisabeth; Andriske, Michael; Paris, Frank; Zhu, Xinran; Lbbert, 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

  2. Ammonia disinfection of animal feeds --laboratory study.

    PubMed

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

    2008-02-29

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

  3. 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.

  4. Mice do not habituate to metabolism cage housing--a three week study of male BALB/c mice.

    PubMed

    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

  5. 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

  6. Differential effect of age on the brain fatty acid levels and their correlation with animal cognitive status in mice.

    PubMed

    Yetimler, Berrak; Ulusoy, Gkhan; elik, Turgay; Jakubowska-Do?ru, Ewa

    2012-11-01

    The aim of the present study was to investigate the possible relationship between the levels of various fatty acids (FA) in the brain and learning indices in aged (2223 months old) and young (23 months old) female Swiss Webster (SW) mice. The mice were classified as good or poor learners based on their performance in a spatial learning task: the Morris Water Maze. The levels of several FA including palmitic, stearic, oleic, linoleic, arachidonic (AA), and docosahexaenoic acid (DHA), were measured by gas chromatography in tissue samples from four different brain areas: hippocampus, frontal cortex, striatum and hypothalamus. The results of behavioral tests confirmed a decline in learning skills with age. However, a great individual variation was revealed in learning scores between aged subjects, indicating that biological aging does not always parallel chronological aging. The relative levels of particular fatty acids across the four examined brain structures were very similar. Interestingly, only in the hypothalamus was the DHA omega-3 acid level significantly higher in young mice compared to the old mice. For the remaining brain structures, no significant correlations were found between the DHA level and the animal's age and/or cognitive status. A significant correlation between learning performance and fatty acid levels in the brain was found only for AA in the young mice hippocampus, a structure known to be critical for spatial learning and memory. The AA level was significantly lower in young good learners compared to both young poor and old good learners with young good learners showing significantly better performance than the two other groups. These findings contribute to the current debate on the value of DHA supplementation as an effective protective treatment against senile dementia and the potential role of AA in memory deficits. PMID:22878041

  7. 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.

  8. Mice selected for high versus low stress reactivity: a new animal model for affective disorders.

    PubMed

    Touma, Chadi; Bunck, Mirjam; Glasl, Lisa; Nussbaumer, Markus; Palme, Rupert; Stein, Hendrik; Wolfersttter, Michael; Zeh, Ramona; Zimbelmann, Marina; Holsboer, Florian; Landgraf, Rainer

    2008-07-01

    Affective disorders such as major depression are among the most prevalent and costly diseases of the central nervous system, but the underlying mechanisms are still poorly understood. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions (hyper- or hypo-activity) of the hypothalamic-pituitary-adrenal (HPA) axis, play a prominent role in the development of major depressive disorders. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel parameters underlying increased or decreased stress reactivity. Starting from a population of outbred mice (parental generation: 100 males and 100 females of the CD-1 strain), two breeding lines were established according to the outcome of a 'stress reactivity test' (SRT), consisting of a 15-min restraint period and tail blood samplings immediately before and after exposure to the stressor. Mice showing a very high or a very low secretion of corticosterone in the SRT, i.e. animals expressing a hyper- or a hypo-reactivity of the HPA axis, were selected for the 'high reactivity' (HR) and the 'low reactivity' (LR) breeding line, respectively. Additionally, a third breeding line was established consisting of animals with an 'intermediate reactivity' (IR) in the SRT. Already in the first generation, i.e. animals derived from breeding pairs selected from the parental generation, significant differences in the reactivity of the HPA axis between HR, IR, and LR mice were observed. Moreover, these differences were found across all subsequent generations and could be increased by selective breeding, which indicates a genetic basis of the respective phenotype. Repeated testing of individuals in the SRT furthermore proved that the observed differences in stress responsiveness are present already early in life and can be regarded as a robust genetic predisposition. Tests investigating the animal's emotionality including anxiety-related behavior, exploratory drive, locomotor activity, and depression-like behavior point to phenotypic similarities with behavioral changes observed in depressive patients. In general, HR males and females were 'hyperactive' in some behavioral paradigms, resembling symptoms of restlessness and agitation often seen in melancholic depression. LR mice, on the other hand, showed more passive-aggressive coping styles, corresponding to signs of retardation and retreat observed in atypical depression. Several morphometric and neuroendocrine findings further support this view. For example, monitoring the circadian rhythm of glucocorticoid secretion revealed clearly increased trough levels in HR mice, resulting in a flattened diurnal rhythm, again adding to the neuroendocrine similarities to patients suffering from melancholic depression. Taken together, our results suggest that distinct mechanisms influencing the function and regulation of the HPA axis are involved in the respective behavioral and neurobiological endophenotypes. Thus, the generated HR/IR/LR mouse lines can be a valuable model to elucidate molecular genetic, neuroendocrine, and behavioral parameters associated with altered stress reactivity, thereby improving our understanding of affective disorders, presumably including the symptomatology and pathophysiology of specific subtypes of major depression. PMID:18502051

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. A high resolution PET for animal studies.

    PubMed

    Watanabe, M; Uchida, H; Okada, H; Shimizu, K; Satoh, N; Yoshikawa, E; Ohmura, T; Yamashita, T; Tanaka, E

    1992-01-01

    In the PET system a block detector, which is a position-sensitive photomultiplier (PMT) tube coupled to four arrays of 1.7-mm-wide BGO crystals, is utilized. Fifteen block detectors are positioned to form a 35-cm-diameter ring, with four BGO arrays coupled to each PMT. This provides four detector rings, giving the system a 7-slice imaging capability. The gantry head tilts up to +/-90 degrees , and is capable of moving up and down by 30 cm. These positioning capabilities allow flexibility and great ease of use in subject positioning. A gantry entrance size of 22 cm in diameter allows studies ranging from rats and mice to primates such as Rhesus and squirrel monkeys. The physical performance of the system has been evaluated. PMID:18222900

  16. 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

  17. 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

  18. 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

  19. 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+CD8?+ lymphoid and CD11c+CD11b+ myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog) was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral therapies in an immunodeficiency context. PMID:21738709

  20. 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.

  1. Inaugurating the Study of Animal Metacognition

    PubMed Central

    Smith, J. David

    2014-01-01

    Metacognitionthe ability to monitor and control ones own cognitionis a sophisticated ability that reveals humans reflective mind and consciousness. Researchers have begun to explore whether animals share humans metacognitive capacity. This article reprises the original study that explored metacognition across species. A captive dolphin performed an auditory pitch-discrimination task using High/Low discrimination responses and an Uncertainty response with which he could decline to complete any trials he chose. He selectively declined the difficult trials near his discriminative thresholdjust as humans do. This comparative exploration of metacognition required a trial-intensive titration of perceptual threshold and the training of a distinctive behavioral response. It could not have been conducted in the wild, though the naturalistic observation of dolphin uncertainty behaviors and risk-management strategies would no doubt yield complementary insights. The dolphin study inaugurated a new area of cross-species research. This research area opens a new window on reflective mind in animals, illuminates the phylogenetic emergence of metacognition, and may reveal the antecedents of human consciousness. PMID:24493908

  2. 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

  3. Animation

    ERIC Educational Resources Information Center

    Bregman, Gene

    1977-01-01

    Establishes the case for animation in projects in the art program, organized for upper elementary through the senior high school level. Describes three simple introductory activities to help students understand the basic theory of animation. (Editor/RK)

  4. 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.

  5. 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

  6. 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…

  7. 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

  8. ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

    PubMed Central

    Lora-Cervera, Elsy Nalleli; Andrade-Narvez, Fernando Jos

    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 1102 and high 1106) 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

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

    PubMed

    S, 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

  10. 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

  11. [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

  12. 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.

  13. 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

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

    NASA Astrophysics Data System (ADS)

    Yarden, Hagit; Yarden, Anat

    2011-12-01

    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 when they watch only animations, mainly due to the cognitive load involved. Moreover, students seem to attribute a great deal of authority to the computer and may develop misconceptions by taking animations of abstract concepts too literally. In this study, we attempted to explore teachers' perceptions concerning the use of animations in the classroom while studying biotechnological methods, as well as the teachers' contribution to the enactment of animations in class. Thirty high-school biotechnology teachers participated in a professional development workshop, aimed at investigating how teachers plan for and support learning with animation while studying biotechnological methods in class. From that sample, two teachers agreed to participate in two case studies aimed at characterizing teachers' contribution to the enactment of animations in class while studying biotechnological methods. Our findings reveal marked teacher contribution in the following three aspects: establishing the "hands-on" point of view, helping students deal with the cognitive load that accompanies the use of animation, and implementing constructivist aspects of knowledge construction while studying using animations.

  15. 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

  16. 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.

  17. 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

  18. 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; Kassa, 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 100mg/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 invivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30mg/kg/day. In contrast, administration at 100mg/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

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

    PubMed Central

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

    2013-01-01

    There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 g/m3, 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust. PMID:23940539

  20. Toxicity of chromated copper arsenate: a study in mice.

    PubMed

    Matos, R C; Vieira, C; Morais, S; Pereira, M L; Pedrosa, J

    2010-07-01

    Chromated copper arsenate (CCA) was widespread used as a chemical wood preservative with application in the construction of playground equipment, fences, jetties, and naval. Environmental protection agency (EPA) had limited the use of CCA-treated wood on 2002, due to probable implications on both human and environmental health. Although this fact, several industries pursue the use of this product within their manufactories. In addition, the durability of this wood for 60 years, makes these treated products an hazard to the public health. In the present work, studies were explored exposing mice to CCA, during 14, 24, 48, and 96 h for the assessment of acute toxicity of CCA. Kidney and liver were removed, prepared for histology and for metalloid, and copper content evaluation by high resolution inductively coupled plasma mass spectroscopy. The histological results evidenced apparently normal structures for control animals and group exposed to As2O5. On the contrary, the renal sections of the animals treated with CCA revealed epithelium cells desquamation, hyaline, and granular casts in renal tubules lumen. Furthermore, high levels of arsenic were detected in the kidney of animals treated with CCA over 14 and 48 h, being significantly greater than controls. Although this approach underlines the potential hazard of CCA on some vital organs, further testing may be required to establish the impacts on other functions. PMID:20307876

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

    PubMed Central

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

    2013-01-01

    The current study was undertaken to investigate potential oncogenic functions of NanogP8, a tumor-specific retrogene homolog of Nanog (expressed in pluripotent cells), in transgenic animal models. To this end, human primary prostate tumor-derived NanogP8 was targeted to the cytokeratin 14 (K14) cellular compartment, and two lines of K14-NanogP8 mice were derived. The line 1 animals, expressing high levels of NanogP8, experienced perinatal lethality and developmental abnormalities in multiple organs, including the skin, tongue, eye, and thymus in surviving animals. On postnatal day 5 transgenic skin, for example, there was increased c-Myc expression and Ki-67+ cells accompanied by profound abnormalities in skin development such as thickened interfollicular epidermis and dermis and lack of hypodermis and sebaceous glands. The line 3 mice, expressing low levels of NanogP8, were grossly normal except cataract development by 46 mo of age. Surprisingly, both lines of mice do not develop spontaneous tumors related to transgene expression. Even more unexpectedly, high levels of NanogP8 expression in L1 mice actually inhibited tumor development in a two-stage chemical carcinogenesis model. Mechanistic studies revealed that constitutive NanogP8 overexpression in adult L1 mice reduced CD34+?6+ and Lrig-1+ bulge stem cells, impaired keratinocyte migration, and repressed the expression of many stem cell-associated genes, including Bmp5, Fgfr2, Jmjd1a, and Jun. Our study, for the first time, indicates that transgenically expressed human NanogP8 is biologically functional, but suggests that high levels of NanogP8 may disrupt normal developmental programs and inhibit tumor development by depleting stem cells. PMID:23839044

  2. 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

  3. Effects of Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) larvae on the degranulation of dermal mast cells in mice; an electron microscopic study.

    PubMed

    Kalender, Yusuf; Kalender, Suna; Uzunhisarcikli, Meltem; Ogutcu, Ay?e; Aikgoz, Fatma

    2004-01-01

    The pine caterpillar Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) is found in pine woods. Hairs of the T. pityocampa caterpillar cause a cutaneous reaction in humans and animals. Mast cells are responsible for allergic reactions in mammals. In this study male swiss albino mice were divided into two groups: 5 mice in the control group and 25 mice in the experimental group. The dorsal skin of mice was shaved. The mice in the experimental group and T. pityocampa larvae (fifth instar, approximately n=100) were put in the same cage. Dermal mast cells of mice exposed to T. pityocampa were examined with a transmission electron microscope and compared to the control group 1, 3, 6, 12 and 24 hours after exposure. Dermal mast cell degranulation in mice was observed 12 and 24 hours after exposure. PMID:15521642

  4. 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.

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

    PubMed

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

    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

  6. Transgenic animal models for study of the pathogenesis of Huntingtons disease and therapy

    PubMed Central

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntingtons disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. PMID:25931812

  7. 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

  8. 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

  9. 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

  10. GPS ERROR IN STUDIES ADDRESSING ANIMAL MOVEMENTS AND ACTIVITES

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. 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.

  12. Megalin Knockout Mice as an Animal Model of Low Molecular Weight Proteinuria

    PubMed Central

    Leheste, Jrg-Robert; Rolinski, Boris; Vorum, Henrik; Hilpert, Jan; Nykjaer, Anders; Jacobsen, Christian; Aucouturier, Pierre; Moskaug, Jan ivind; Otto, Albrecht; Christensen, Erik Ils; Willnow, Thomas E.

    1999-01-01

    Megalin is an endocytic receptor expressed on the luminal surface of the renal proximal tubules. The receptor is believed to play an important role in the tubular uptake of macromolecules filtered through the glomerulus. To elucidate the role of megalin in vivo and to identify its endogenous ligands, we analyzed the proximal tubular function in mice genetically deficient for the receptor. We demonstrate that megalin-deficient mice exhibit a tubular resorption deficiency and excrete low molecular weight plasma proteins in the urine (low molecular weight proteinuria). Proteins excreted include small plasma proteins that carry lipophilic compounds including vitamin D-binding protein, retinol-binding protein, ?1-microglobulin and odorant-binding protein. Megalin binds these proteins and mediates their cellular uptake. Urinary loss of carrier proteins in megalin-deficient mice results in concomitant loss of lipophilic vitamins bound to the carriers. Similar to megalin knockout mice, patients with low molecular weight proteinuria as in Fanconi syndrome are also shown to excrete vitamin/carrier complexes. Thus, these results identify a crucial role of the proximal tubule in retrieval of filtered vitamin/carrier complexes and the central role played by megalin in this process. PMID:10514418

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

    PubMed Central

    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 710days. Those cases which fail to heal within 3months 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, 19days), 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

  15. 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.

  16. 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.

  17. Reviewing existing knowledge prior to conducting animal studies.

    PubMed

    Knight, Andrew

    2008-12-01

    Highly polarised viewpoints about animal experimentation have often prevented agreement. However, important common ground between advocates and opponents was demonstrated within a discussion forum hosted at www.research-methodology.org.uk in July-August 2008, by the independent charity, SABRE Research UK. Agreement existed that many animal studies have methodological flaws - such as inappropriate sample sizes, lack of randomised treatments, and unblinded outcome assessments - that may introduce bias and limit statistical validity. There was also agreement that systematic reviews of the human utility of animal models yield the highest quality of evidence, as their reliance on methodical and impartial methods to select significant numbers of animal studies for review, serves to minimise bias. Unfortunately, disagreement remained that animal experimental licence applications should reference systematic reviews of existing studies, before approval. The UK Medical Research Council requires that researchers planning human clinical trials must reference such reviews of related previous work. Existing knowledge is thereby fully and appropriately utilised, and redundant experimentation is avoided. However, objections were raised that a similar requirement would interfere with animal experimental licensing, because, to date, there have been very few systematic reviews of animal studies. In fact, the relative dearth of such reviews is a matter of considerable concern, and may partially explain the very poor human success rates of drugs that appear safe and/or efficacious in animal trials. Nevertheless, the disturbing number of human trials which have proceeded concurrently with, or prior to, animal studies, or have continued despite equivocal evidence of efficacy in animals, clearly demonstrate that many researchers fail to conduct adequate prior reviews of existing evidence. Where neither sufficient primary studies, nor systematic reviews of such studies, exist, for citation within a licence application, researchers should be able to provide evidence of this shortcoming, and, concurrently, demonstrate that the available literature and evidence have been adequately reviewed. This should also enable them to clearly demonstrate the need and scientific appropriateness of their proposed study, the validity of its design, and - importantly - that the benefits are reasonably likely to exceed the animal welfare, bioethical and financial costs. Invasive animal studies should never be permitted solely on the basis of less probable, speculative or intangible human benefits, or the mere satisfaction of scientific curiosity. PMID:19154097

  18. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    PubMed

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, Mara L; Muoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, ? subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-? (PPAR?), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD. PMID:25252936

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Studies on anthrax in food animals and persons occupationally exposed to the zoonoses in Eastern Nigeria.

    PubMed

    Okolo, M I

    1985-12-01

    A total of 221 blood and 174 carcase swab samples obtained from food animals (cattle, sheep, goats, pigs and horses) slaughtered at urban and rural slaughter houses in Nsukka area were studied. 51 blood samples and 180 samples of vesicle fluid were also collected from persons occupationally exposed (butchers/skinners, meat retailers, meat inspectors, veterinarians and tanners) to these animals and their products. All the samples were studied culturally and microscopically. Confirmation of infection was by subcutaneous inoculation of guinea pigs and mice with samples of human and animal blood, carcase swabs and vesicle fluid got from suspected cutaneous lesions on the hands of persons studied in this survey. Of the blood samples obtained from food animals, 5 per cent (3/60) of cattle and 3.3 per cent (1/30) of sheep were positive. The rest of the blood samples from other animals were negative. For the carcase swab samples, 5.7 per cent (5/88) from cattle and 3.1 per cent (1/33) from sheep were positive. The rest of the carcase swabs from goats, pigs and horses were negative. Only the blood samples from butchers/skinners, 20 per cent (2/10), meat retailers, 9.1 per cent (1/11) and tanners, 11.1 per cent (1/9) were positive. Malignant pustule was confirmed in 13.3 per cent (6/45) of butchers/skinners, 10 per cent (3/30) of tanners and 6 per cent (3/50) of meat retailers. The results show that food animals and their products constitute a potential danger to those persons whose occupation necessitates handling animal products or contact with animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3836213

  4. Controlling airborne cues to study small animal navigation.

    PubMed

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

    2012-03-01

    Small animals such as 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 precisely controlling stimuli. We present a system that can be used to deliver gaseous stimuli in defined spatial and temporal patterns to freely moving small animals. We used this apparatus, in combination with machine-vision algorithms, to assess and quantify navigational decision making of Drosophila melanogaster larvae in response to ethyl acetate (a volatile attractant) and carbon dioxide (a gaseous repellant). PMID:22245808

  5. 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

  6. Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

    PubMed Central

    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 incabinet; two such cabinets (16 environments) may be controlled by one computer. PMID:24637442

  7. 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

  8. Defective bone microstructure in hydronephrotic mice: a histomorphometric study in ICR/Mlac-hydro mice.

    PubMed

    Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Ampawong, Sumate; Krishnamra, Nateetip; Kengkoom, Kanchana; Charoenphandhu, Narattaphol

    2014-02-01

    Chronic renal impairment can lead to bone deterioration and abnormal bone morphology, but whether hydronephrosis is associated with bone loss remains unclear. Herein, we aimed to use computer-assisted bone histomorphometric technique to investigate microstructural bone changes in Imprinting Control Region (ICR) mice with a spontaneous mutation that was associated with bilateral nonobstructive hydronephrosis (ICR/Mlac-hydro). The results showed that 8-week-old ICR/Mlac-hydro mice manifested decreases in trabecular bone number and thickness, and an increased trabecular separation, thereby leading to a reduction in trabecular bone volume compared with the wild-type mice. Furthermore, histomorphometric parameters related to both bone resorption and formation, that is, eroded surface, osteoclast surface, and osteoblast surface, were much lower in ICR/Mlac-hydro mice than in the wild type. A decrease in moment of inertia was found in ICR/Mlac-hydro mice, indicating a decrease in bone strength. In conclusion, ICR/Mlac-hydro mice exhibited trabecular bone loss, presumably caused by marked decreases in both osteoblast and osteoclast activities, which together reflected abnormally low bone turnover. Thus, this mouse strain appeared to be a valuable model for studying the hydronephrosis-associated bone disease. PMID:24227694

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. [Effects of valerian root oil, borneol, isoborneol, bornyl acetate and isobornyl acetate on the motility of laboratory animals (mice) after inhalation].

    PubMed

    Buchbauer, G; Jger, W; Jirovetz, L; Meyer, F; Dietrich, H

    1992-08-01

    The aromatherapeutical use of commercial valerian root oil (Chinese origin) and of pure fragrance compounds--borneol, isoborneol, bornyl acetate (main constituent of the proved valerian root oil) and isobornyl acetate--as potentially drugs with sedative effects after inhalation was investigated in an animal experiment (mice). In additional analyses the mice were treated i.p. by caffeine and distinct sedative effects were observed only by inhalation of the cited substances. PMID:1438515

  15. 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

  16. 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

  17. 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

  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. 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

  1. 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.

  2. A preliminary study on antimetastatic activity of Thuja occidentalis L. in mice model.

    PubMed

    Sunila, E S; Kuttan, G

    2006-01-01

    The effect of Thuja occidentalis extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. The extract was administered by three different modalities. A remarkable reduction in tumor-nodule formation was shown by simultaneous (74.4%) and prophylactic (71.5%) mode of administration. The effect was comparatively low in drug administration after tumor development (60.2%). Increased lung collagen hydroxyproline (21.13 microg/mg protein) in the metastasized lungs of control animals compared with normal animals (0.98 microg/mg protein) was significantly reduced in Thuja-treated animals. The elevated level of uronic acid (349.5 microg/100 mg tissue) and hexosamine contents in metastatic control animals was significantly reduced in the animals treated with alcoholic extract of Thuja. Similarly the elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with the extract of Thuja. The lifespan of the Thuja treated animals also was seen to be significantly increased. PMID:16873095

  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, drugdrug interactions, and for short- and long-term investigation of the toxicity of drugs or chemicals with significant human exposure. PMID:20645070

  4. Studies of macrophage function during Trichinella spiralis infection in mice.

    PubMed Central

    Wing, E J; Krahenbuhl, J L; Remington, J S

    1979-01-01

    Studies were made to investigate the quantitative and functional changes which occur in peritoneal macrophage populations obtained from mice infected orally with Trichinella spiralis larvae. C57BL/6 mice infected with T. spiralis larvae became parasitized with adult worms which were rejected from the intestine from 14 to 20 days after infection. Infected mice developed a striking increase in peritoneal exudate cells, composed largely of macrophages, which was maximal at from 16 to 18 days after infection. T. spiralis larvae and eosinophils were not seen in the peritoneal exudates. Macrophages from mice infected more than 11 days earlier inhibited DNA synthesis of syngeneic and allogeneic tumour cells, a property atributed to activated macrophages. In addition, macrophages from T. spiralis-infected mice had the functional ability to kill EL-4 tumour cells as measured by 51Cr release. Unlike activated macrophages, however, macrophages from infected mice did not develop the ability to inhibit multiplication of the intracellular pathogen Toxoplasma gondii. These studies demonstrate that T. spiralis infection in mice induces changes in macrophage function that differ from changes associated with infections by intracellular pathogens. PMID:437839

  5. 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

  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. 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…

  8. 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

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

    PubMed

    Corpet, Denis E; Pierre, Fabrice

    2003-05-01

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

  10. Older people's relationships with companion animals: a pilot study.

    PubMed

    Prosser, Lauren; Townsend, Mardie; Staiger, Petra

    2008-04-01

    When older people enter residential care facilities, disruption to social networks may occur, with detrimental effects on health and wellbeing. This article reports on a study undertaken in an aged care facility in Melbourne, Australia, that explored the potential for a visiting companion animal programme to improve the health and wellbeing of residents and to promote their capacity for building relationships. Results back assertions in the literature that companion animals foster relationships by giving people opportunities to interact with others, but further study is needed to verify the link. PMID:18500131

  11. [Study on Raman Spectra of Some Animal and Plant Oils].

    PubMed

    Wang, Xiang; Dai, Chang-jian

    2015-04-01

    The spectral characteristics of different kinds of oil, either from plant seeds or animal fat, were studied with Raman spectroscopy. The experimental data were processed with the adaptive iteratively reweighted penalized least squares method to realize baseline correction, and provide evident information about their microscopic world. The spectra were analyzed and compared with each other in three parts: the Raman spectra comparison among different samples of plant oils, the analysis of the animal fat and the comparison between plant oils and the animal fat. The differences among the oils were observed in the analysis, including Raman shift and Raman intensity differences. This study not only yields the spectral basis for distinguishing or recognizing the different edible oils, but also confirms that Raman spectroscopy is an effective tool for identifying different oils. PMID:26197577

  12. 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

  13. 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

  14. 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

  15. 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 ?g/kgBW (95% CI: 383535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 ?g/kgBW (95% CI: 362566) and 447 ?g/kgBW (95% CI: 378504 ?g/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 ?g/kgBW (95% CI: 442517). 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

  16. [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

  17. [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

  18. 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

  19. A reproducible nonlethal animal model for studying cyanide poisoning.

    PubMed

    Vick, J; Marino, M T; von Bredow, J D; Kaminskis, A; Brewer, T

    2000-12-01

    Previous studies using bolus intravenous injections of sodium cyanide have been used to model the sudden exposure to high concentrations of cyanide that could occur on the battlefield. This study was designed to develop a model that would simulate the type of exposure to cyanide gas that could happen during actual low-level continuous types of exposure and then compare it with the bolus model. Cardiovascular and respiratory recordings taken from anesthetized dogs have been used previously to characterize the lethal effects of cyanide. The intravenous, bolus injection of 2.5 mg/kg sodium cyanide provides a model in which a greater than lethal concentration is attained. In contrast, our model uses a slow, intravenous infusion of cyanide to titrate each animal to its own inherent end point, which coincides with the amount of cyanide needed to induce death through respiratory arrest. In this model, therapeutic intervention can be used to restore respiration and allow for the complete recovery of the animals. After recovery, the same animal can be given a second infusion of cyanide, followed again by treatment and recovery, providing a reproducible end point. This end point can then be expressed as the total amount of cyanide per body weight (mg/kg) required to kill. In this study, the average dose of sodium cyanide among 12 animals was 1.21 mg/kg, which is approximately half the cyanide used in the bolus model. Thus, titration to respiratory arrest followed by resuscitation provides a repetitive-use animal model that can be used to test the efficacy of various forms of pretreatment and/or therapy without the loss of a single animal. PMID:11149071

  20. 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; Vigan, 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

  1. 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; Vigan, 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, epidermaldermal 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

  2. Fourier transform Raman spectroscopic studies of human and animal skins

    NASA Astrophysics Data System (ADS)

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

    1994-01-01

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

  3. 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

  4. The role of animal models in the study of varicocele

    PubMed Central

    Katz, Matthew J.; Li, Philip S.; Goldstein, Marc

    2014-01-01

    Varicocele is the most common correctible cause of male infertility and is present in 15% to 20% of the male population. Despite its prevalence, the pathophysiology of varicocele remains under investigation. One of the largest obstacles in studying varicocele is that it is almost exclusively found in humans. This has necessitated the creation of an animal model of varicocele. The most commonly used animal model involves the creation of a varicocele in a rodent by partially occluding the left renal vein. This model has provided a significant amount of data on varicocele, and a modification of this model utilizing microsurgery appears even more promising. Animal models have proven critical to investigating the pathophysiology of varicocele.

  5. Experimental animal studies of radon and cigarette smoke

    SciTech Connect

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

    1992-12-31

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

  6. Reinforcing properties of caffeine: studies in humans and laboratory animals.

    PubMed

    Griffiths, R R; Woodson, P P

    1988-02-01

    Three types of experimental studies are reviewed: (1) intravenous and oral caffeine self-administration by laboratory animals, (2) oral caffeine self-administration by humans, and (3) human subjective effects of caffeine relevant to reinforcing effects. These studies show that, under appropriate conditions, caffeine can serve as a reinforcer and can produce elevations in subjective drug liking and/or euphoria. In this regard, caffeine can be distinguished from a wide range of behaviorally active compounds, such as the amphetamine analog fenfluramine and the major tranquilizer chlorpromazine, which do not produce such effects. Caffeine can also be distinguished from classic drugs of abuse such as cocaine, d-amphetamine or pentobarbital which generally maintain high levels of self-administration (or liking) in contrast to caffeine which tends to maintain lower levels of self-administration (or liking) or maintain self-administration under a more narrow range of parametric conditions. Several human studies and one animal experiment suggest that physical dependence substantially potentiates the reinforcing effects of caffeine. Other human and animal studies indicate that there may be substantial differences between individual subjects in the reinforcing effects of caffeine. An important challenge for future human and animal drug self-administration research will be to delineate more precisely the conditions under which caffeine does and does not serve reliably as a reinforcer. PMID:3283780

  7. 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…

  8. [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

  9. 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…

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies.

    PubMed

    Wickremsinhe, Enaksha R; Perkins, Everett J

    2015-03-01

    Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 ?L 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 ?L), 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

  15. 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 L blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animaloften to a single collection per mousethus 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 L), 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

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

    PubMed Central

    Cellot, Giada; Cherubini, Enrico

    2014-01-01

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

  17. Lung Resection Using Transumbilical Incision: An Animal Survival Study

    PubMed Central

    Yin, Shun-Ying; Yen-Chu; Wu, Yi-Cheng; Liu, Chien-Ying; Hsieh, Ming-Ju; Yuan, Hsu-Chia; Ko, Po-Jen

    2015-01-01

    Introduction: Transumbilical single-port surgery is a potentially less invasive approach to many types of abdominal surgeries and offers better cosmetic outcomes than conventional 3-port laparoscopic surgery. It avoids the complication of intercostal neuralgia and may reduce the risk of pulmonary complications after video-assisted thoracic surgery. This study evaluated the feasibility of transumbilical lung wedge resection. Methods: Lung resection was performed in 11 beagle dogs weighing 5.9 to 8.5 kg. A 3-cm umbilical incision and one diaphragmatic incision were made, and an endoscopic stapler was used. The diaphragmatic incisions were repaired under video guidance using a V-Loc knotless suturing device (Covidien, Mansfield, Massachusetts). Animals were monitored daily for signs of postoperative infection. White blood cell count, C-reactive protein level, and IL-6 level were measured in all animals. Animals were euthanized 14 days after surgery and underwent necropsy evaluation. Results: Accurate lung resection was achieved in 10 of 11 animals during a median operative time of 98 minutes (range 60165). In 1 animal, transumbilical lung resection was not possible and was converted to thoracotomy. All animals survived without major postoperative complications. At necropsy, evidence of uneventful healing of the stapled resection margin and diaphragmatic wound were found. There was no evidence of vital organ injury or intrathoracic infection. Conclusion: A transumbilical approach to thoracic cavity exploration and stapled lung resection is technically feasible. Primary suturing of the diaphragmatic incision is a simple and effective means of diaphragmatic wound closure. This may be an alternative to video-assisted thoracic surgery for the management of simple thoracic disease. PMID:25848173

  18. 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.

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

    PubMed

    Grsser-Cornehls, U; Grsser, C; Burle, 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

  20. 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

  1. 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

  2. Study of anti-angiogenic drugs by fluorescence imaging and spectroscopy of a contrast agent in mice

    NASA Astrophysics Data System (ADS)

    Valentini, G.; D'Andrea, C.; Ferrari, R.; Pifferi, A.; Cubeddu, R.; Caronia, D.; Martinelli, M.; Giavazzi, R.

    2007-07-01

    We used two fluorescence techniques based on the Indocyanine Green contrast agent to study the effectiveness of antiangionenic drugs in mice. To this purpose, the volume of the active vasculature in different tumor models implanted in mice was assessed by means of a low noise fluorescence imaging setup and by a photon counting system working in transmittance geometry. Using a first tumor model (carcinoma MDA-MB-435) we observed that mice treated with a Vascular Disrupting Agent (ZD6126) showed a reduction in fluorescence emission of the contrast agent with respect to control mice. This was a clear indication of the vascular shutdown that took place in tumors. The effectiveness of the treatment was also confirmed by histological sections. Then, in a second experiment we considered a second tumor model (carcinoma 1A9-VS1) overexpressing the Vascular Endotelial Growth Factor (VEGF121), which is used by tumor cells to promote angiogenesis. We measured the Indocyanine Green fluorescence in mice treated with an antioangiogenic drug (Avastin TM) and in control mice. In tumors of treated mice we observed an ICG emission lower than the one detected in control mice. This demonstrated that VEGF activity was effectively blocked by the treatment with Avastin. In conclusion, ICG fluorescence provides a simple and reliable way to assess the effectiveness of vascular targeting therapies. Measurements of the fluorescence signal can be repeated every 24 hours, thus allowing oncologists to perform longitudinal studies on the same animals.

  3. Autobacteriographic studies of clarithromycin and erythromycin in mice

    SciTech Connect

    Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. )

    1990-04-01

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

  4. 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; Gonalves, Cinara L; Ferreira, Gabriela K; Rus, Gislaine Z; Resende, Wilson R; Valvassori, Samira S; Kapczinski, Flvio; Andersen, Mnica L; Quevedo, Joo

    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

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

    PubMed Central

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

    2014-01-01

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

  6. Rodents for comparative aging studies: from mice to beavers

    PubMed Central

    Bozzella, Michael J.; Seluanov, Andrei

    2008-01-01

    After humans, mice are the best-studied mammalian species in terms of their biology and genetics. Gerontological research has used mice and rats extensively to generate short- and long-lived mutants, study caloric restriction and more. Mice and rats are valuable model organisms thanks to their small size, short lifespans and fast reproduction. However, when the goal is to further extend the already long human lifespan, studying fast aging species may not provide all the answers. Remarkably, in addition to the fast-aging species, the order Rodentia contains multiple long-lived species with lifespans exceeding 20years (naked mole-rat, beavers, porcupines, and some squirrels). This diversity opens great opportunities for comparative aging studies. Here we discuss the evolution of lifespan in rodents, review the biology of slow-aging rodents, and show an example of how the use of a comparative approach revealed that telomerase activity coevolved with body mass in rodents. PMID:19424861

  7. Immunotoxicology of arc welding fume: worker and experimental animal studies.

    PubMed

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

    2012-01-01

    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

  8. 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

  9. 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.

  10. 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

  11. Significance of ecological studies of wild animal reservoirs of zoonoses

    PubMed Central

    Abdussalam, M.

    1959-01-01

    The paucity of information on the ecology of wild animal reservoirs over most of the world is one of the factors that has led to hesitation and failure in controlling these diseases in many areas. Extensive application of ecological studies and methods would not only assist in zoonosis control but might well also lead to the discovery of new diseases, to the acquisition of fundamental knowledge capable of application in other fields of biology, and to the finding of new experimental animals for laboratory work. Although such studies properly require the co-operation of a wide variety of specialistsepidemiologists, ecologists, parasitologists, botanists, geologists and climatologists are among those who may to advantage be called uponin practice much can be accomplished by a few interested and well-equipped field workers backed by a good museum and laboratory services. PMID:13791420

  12. 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.

  13. 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).

  14. 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

  15. 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.

  16. Study of the dynamic expression of Meis1 in mice

    PubMed Central

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

    2013-01-01

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

  17. A review of toxicity studies of single-walled carbon nanotubes in laboratory animals.

    PubMed

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-02-01

    We summarized the findings of invivo toxicity studies of single-walled carbon nanotubes (SWCNTs) in laboratory animals. The large majority addressed the pulmonary toxicity of SWCNTs in rodents. Inhalation, pharyngeal aspiration, and intratracheal instillation studies revealed that SWCNTs caused acute and chronic inflammation, granuloma formation, collagen deposition, fibrosis, and genotoxic effects in the lungs. Pulmonary toxicity of well-dispersed SWCNTs was more potent than less dispersed ones. Airway exposure to SWCNTs also induced cardiovascular diseases in mice. Oxidative stress was caused by the administration of SWCNTs. Injected SWCNTs were distributed throughout most of the organs including the brain, mainly retained in the lungs, liver, and spleen, and eliminated through the kidney and bile duct. Orally administered SWCNTs are suggested to be absorbed from the gastrointestinal tract to the blood circulation in mice and rats. Although no definitive study on the carcinogenicity of SWCNTs is available at present, evidence of carcinogenicity has not been reported in toxicity studies cited in this review. Overall, the available data provides initial information on SWCNT toxicity. To further clarify their toxicity and risk assessment, studies should be conducted using well-characterized SWCNTs, standard protocols, and the relevant route and doses of human exposure. PMID:26619783

  18. 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.

  19. 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

  20. 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

  1. [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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Study of two devices used to maintain normothermia in rats and mice during general anesthesia.

    PubMed

    Taylor, Douglas K

    2007-09-01

    Rodents are very susceptible to hypothermia during anesthetic events because of their high body surface-to-mass ratio. This study examined the effectiveness of 2 heating devices, a heatpad and a circulating hot-water blanket, during 60 min of isoflurane general anesthesia in rats and mice (n = 6 per treatment). In addition, 1 control group of animals for each species was anesthetized with no heat source (n = 6). Both devices carried minimal risk of causing thermal burns or hyperthermia. Rats on the circulating water blanket showed a slight decrease (0.11 +/- 0.19 degrees C) from the initial (time 0) body temperature (mean +/- standard error), whereas the heatpad was associated with a significant increase (0.96 +/- 0.10 degrees C). Mice on the circulating water blanket showed a significant decrease (0.46 +/- 0.05 degrees C) in body temperature. The trend in mice on the heatpad was similar to that in rats, with a significant increase (0.94 +/- 0.13 degrees C) from the body temperature at time 0. Although statistically significant, these deviations from baseline body temperature were not considered physiologically relevant. In comparison, body temperatures decreased significantly in rats and mice (4.42 +/- 0.60 and 9.90 +/- 0.35 degrees C, respectively) with no heat source. Both heating devices were safe and effective, but the low cost, ease of maintenance, and portability of the heatpad may make it a more desirable choice in some facilities. PMID:17877326

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Potential for clonal animals in longevity and ageing studies.

    PubMed

    Nilsson Skld, Helen; Obst, Matthias

    2011-10-01

    Ageing is defined as a decline in reproductive and/or somatic performance over time, and as such is experienced by most organisms. Evolutionary theories explain ageing as a consequence of reduced selection pressure against mutations and reduced allocation to somatic maintenance in post-reproductive individuals. In addition, the fecundity of younger age-groups makes a more significant contribution than infinite maintenance of the parental body to the production of subsequent generations. However, in clonal animals, as well as in plants that reproduce by agametic cloning, the adult body is itself a reproductive unit that increases its fitness as a function of genet size. Given the apparent longevity of many such clonal organisms, species undergoing agametic cloning are often assumed to be non-ageing and even potentially immortal. Here, we present a brief overview of ageing in organisms undergoing agametic cloning, focusing on animals and molecular investigation. We discuss molecular and evolutionary aspects of ageing or non-ageing with respect to selection in clonal species. Of particular relevance to the search for potential mechanistic processes behind longevity is the notion that clonal organisms are frequently smaller than their obligate sexual counterparts. In conclusion, we find that while clonal animals also commonly age, evolutionary arguments together with empirical evidence suggest that they are likely to be long-lived and stress resistant at the genet level. However, theoretical modeling continues to predict the possibility of immortality, if the contribution from sexual reproduction is low. Future in-depth study of long-lived clones should present an excellent opportunity to discover novel mechanisms for renewal and long-term somatic maintenance and health. PMID:21479578

  18. 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.

  19. 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, Mnica; Fernandes, Luciana Caetano; Hoffman Pfrimer, Irmtraut Araci; Pichiteli, Cssia 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-? 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

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

    PubMed

    Spadafora-Ferreira, Mnica; Fernandes, Luciana Caetano; Hoffman Pfrimer, Irmtraut Araci; Pichiteli, Cssia 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-2(a) 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-gamma 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

  1. Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone.

    PubMed

    Cavalletti, Ennio; Crippa, Luca; Mainardi, Patrizia; Oggioni, Norberto; Cavagnoli, Rosanna; Bellini, Ornella; Sala, Franca

    2007-06-01

    Anthracyclines and anthracenediones are important oncotherapeutics; however, their use is associated with irreversible and cumulative cardiotoxicity. A novel aza-anthracenedione, pixantrone (BBR 2778), was developed to reduce treatment-related cardiotoxicity while retaining efficacy. This study evaluates the cumulative cardiotoxic potential of pixantrone compared with equiactive doses of doxorubicin and mitoxantrone in both doxorubicin-pretreated and doxorubicin-nave mice. CD1 female mice were given doxorubicin 7.5 mg/kg (once weekly for 3 weeks) followed 6 weeks later by either sterile 0.9% saline, doxorubicin 7.5 mg/kg, pixantrone 27 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). A second group of CD1 female mice were given 2 cycles of either sterile 0.9% saline, pixantrone 27 mg/kg, doxorubicin 7.5 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). Animals were sacrificed at different time points for histopathologic examination of the heart. In the doxorubicin-pretreated mice, further exposure to doxorubicin or mitoxantrone resulted in a significant worsening of pre-existing degenerative cardiomyopathy. In contrast, pixantrone did not worsen pre-existing cardiomyopathy in these animals. Only minimal cardiac changes were observed in mice given repeated cycles of pixantrone, while 2 cycles of doxorubicin or mitoxantrone resulted in marked or severe degenerative cardiomyopathy. These animal studies demonstrate the reduced cardiotoxic potential of pixantrone compared with doxorubicin and mitoxantrone. Exposure to pixantrone did not worsen pre-existing cardiomyopathy in doxorubicin-pretreated mice, suggesting that pixantrone may be useful in patients pretreated with anthracyclines. PMID:17285358

  2. 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... demonstrated in more than one animal species expected to react with a response predictive for humans,...

  3. 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... demonstrated in more than one animal species expected to react with a response predictive for humans,...

  4. 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... demonstrated in more than one animal species expected to react with a response predictive for humans,...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  7. Choosing the Correct AED: From Animal Studies to the Clinic

    PubMed Central

    Holmes, Gregory L.; Zhao, Qian

    2009-01-01

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

  8. 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

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

    PubMed Central

    Metcalfe, Janet; Jacobs, W. Jake

    2010-01-01

    In this article we suggest a relation between people's metacognitively guided study time allocation strategies and animal foraging. These two domains are similar insofar as people use specific metacognitive cues to assist their study time allocation just as other species use cues, such as scent marking. People decline to study items that they know they already know, just as other species use a win-shift strategy avoiding already visited and depleted patches in foraging. People selectively study the easiest as-yet-unlearned items first, before turning to more difficult items just as other species take the just right size and challenge of prey--the so-called Goldilocks principle. People use a stop rule by which they give up on one item and turn to another when the returns diminish just as others species use a stop rule that guides shifting from one patch to another. The value that each item is assigned on the criterion test, if known during study, influenced which items people choose to study and how long they study them just as knowledge of the nutritional or energy value of the food influences choices and perseverance in foraging. Finally, study time allocation strategies can differ in their effectiveness depending upon the expertise of the student just as some species forage close to optimally while others do not. PMID:20026197

  10. 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

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

    PubMed

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

    2015-01-01

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

  12. 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

  13. Animal modeling of cancer pathology and studying tumor response to therapy.

    PubMed

    Langdon, Simon P

    2012-11-01

    Animal models of human cancer have evolved in attempts to capture the complexity of the human disease. They encompass two broad types of model, namely those in which the tumor arises in situ and those in which cancer cells or tissue are transplanted. Currently human tumor xenografts are the most widely used model to help predict antitumor efficacy in a preclinical setting and xenograft results for certain disease types such as ovarian cancer and non-small cell lung cancer correlate well with clinical activity if the models are used under appropriate conditions. The genetically engineered mouse (GEM) models allow study of the effects of targeted inhibitors against defined molecular targets. These are becoming increasingly sophisticated to recapitulate the progression of tissue-specific molecular changes found within individual cancers. Non-germline GEM models possess the ability to study the impact of specific cancer genes without some of the limitations inherent in traditional GEM models. While rodents, particularly mice, have been the animal host most frequently used, there is increasing recognition of the value of using larger species especially dogs in the veterinary oncology setting. These have successfully modelled aspects of selected human cancers such as osteosarcoma, GIST and prostate cancer. Individually, these models have relative strengths and weaknesses in mimicking the human disease and appropriately reflecting its cellular and molecular pathology. This review will seek to address where these models can be best used to help predict response to therapeutics. PMID:22974396

  14. 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)

  15. 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

  16. 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

  17. 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

  18. 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

  19. Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

    PubMed Central

    Sarkar, Dipak K.

    2010-01-01

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

  20. 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.

  1. 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

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

    PubMed

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

    2014-01-01

    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

  3. 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

  4. CAGE FOR USE WITH SMALL AQUATIC ANIMALS IN FIELD STUDIES

    EPA Science Inventory

    Various cages are frequently used in assessing the effects of pesticides on non-target animals. In some cases, small animals offer advantages over larger ones because they may be more economical to raise in the laboratory or to purchase; immature stages often are more sensitive t...

  5. 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.

  6. 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.…

  7. 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.

  8. 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

  9. A longitudinal FDG-PET study of transgenic mice overexpressing GSK- 3? in the brain.

    PubMed

    de Cristbal, Javier; Garcia-Garcia, Luis; Delgado, Mercedes; Pozo, Miguel A; Medina, Miguel

    2014-02-01

    Increased Glycogen synthase kinase-3 (GSK-3) activity is believed to contribute to the etiology of chronic disorders such as Alzheimer's disease, one of the earliest diseases linked to GSK-3 dysfunction. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect of GSK-3 inhibitors. In this study we have characterised and evaluated the brain metabolic changes induced by GSK-3? overexpression in transgenic mice throughout their lifespan. The conditional Tet/GSK-3? transgenic line used in this study has been previously extensively characterized at the pathological, biochemical and cognitive levels. Now we have investigated the effect GSK-3? overexpression on the (18)F-fluoro-deoxyglucose (FDG) uptake by positron emission tomography (PET), taking advantage from this non-invasive technique which has allowed us to track individually the same animals throughout their lives. The results obtained during the longitudinal analysis showed a reduction of metabolic activity in several brain regions, such as cortex, striatum and hippocampus, consistent with the areas where the transgene is being expressed. The reduction of the metabolic activity in these mice is observed from the first time point, performed at the age of 3 months, and maintained throughout the whole study, until the oldest age tested (19 months). This effect seems to be reverted in a satellite group of 3-month transgenic animals treated with the classical GSK-3 inhibitor lithium, as they show higher FDG uptake values compared with untreated age-matched transgenic animals. PMID:23905999

  10. 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.

  11. 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.

  12. 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

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

    PubMed

    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

  14. Mouse Studies to Shape Clinical Trials for Mitochondrial Diseases: High Fat Diet in Harlequin Mice

    PubMed Central

    Schiff, Manuel; Bnit, Paule; El-Khoury, Riyad; Schlemmer, Dimitri; Benoist, Jean-Franois; Rustin, Pierre

    2011-01-01

    Background Therapeutic options in human mitochondrial oxidative phosphorylation (OXPHOS) diseases have been poorly evaluated mostly because of the scarcity of cohorts and the inter-individual variability of disease progression. Thus, while a high fat diet (HFD) is often recommended, data regarding efficacy are limited. Our objectives were 1) to determine our ability to evaluate therapeutic options in the Harlequin OXPHOS complex I (CI)-deficient mice, in the context of a mitochondrial disease with human hallmarks and 2) to assess the effects of a HFD. Methods and Findings Before launching long and expensive animal studies, we showed that palmitate afforded long-term death-protection in 3 CI-mutant human fibroblasts cell lines. We next demonstrated that using the Harlequin mouse, it was possible to draw solid conclusions on the efficacy of a 5-month-HFD on neurodegenerative symptoms. Moreover, we could identify a group of highly responsive animals, echoing the high variability of the disease progression in Harlequin mice. Conclusions These results suggest that a reduced number of patients with identical genetic disease should be sufficient to reach firm conclusions as far as the potential existence of responders and non responders is recognized. They also positively prefigure HFD-trials in OXPHOS-deficient patients. PMID:22174907

  15. 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

  16. 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

  17. 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.

  18. 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 ...

  19. 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.

  20. 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

  1. 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. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26467890

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

    PubMed

    Mousseau, Timothy A; Mller, 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

  3. 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

  4. Small animals in the study of pathological effects of asbestos

    PubMed Central

    Holt, Paul F.

    1974-01-01

    The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 ?m long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. This clearance mechanism is inhibited by other factors: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs. ImagesFIGURE 1.FIGURE 2.FIGURE 3.FIGURE 4.FIGURE 5. PMID:4377872

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

    PubMed

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

    2012-05-01

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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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 ?m x 100 ?m 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 ?m and an axial resolution of 2.5 ?m. Therefore, the developed widefield multiphoton microscopy can provide fast and high-resolution multiphoton excited fluorescence images for animal study in vivo.

  11. 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

  12. 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

  13. Comparison of Ehrlichia muris strains isolated from wild mice and ticks and serologic survey of humans and animals with E. muris as antigen.

    PubMed

    Kawahara, M; Ito, T; Suto, C; Shibata, S; Rikihisa, Y; Hata, K; Hirai, K

    1999-04-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had been isolated. These new isolates were compared with the E. muris type strain. The mouse virulence and ultrastructure of the new isolates were similar to those of the type strain, and all of them were cross-reactive with each other, as well as with the type strain, by indirect immunofluorescent-antibody test. The levels of similarity of the base sequences of the 16S rRNA gene of one of the A. speciosus isolates and one of the tick isolates to that of the E. muris type strain were 99.79 and 99.93%, respectively. We suggest that all of these isolates are E. muris; that E. muris is not limited to Eothenomys kageus but infects other species of mice; and that E. muris is present at locations other than Aichi Prefecture. It appears that H. flava is a potential vector of E. muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be seropositive for E. muris antibodies. A serological survey revealed that exposure to E. muris or organisms antigenically cross-reactive to E. muris occurred among dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby prefectures, and Nagoya City, central Japan. However, human beings and Rattus norvegicus rats in this area were seronegative. These results indicate broader geographic distribution of and human and animal species exposure to E. muris or related Ehrlichia spp. in Japan. PMID:10074536

  14. 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

  15. 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

  16. A single-dose toxicity study on non-radioactive iodinated hypericin for a targeted anticancer therapy in mice

    PubMed Central

    Li, Jun-jie; Cona, Marlein Miranda; Feng, Yuan-bo; Chen, Feng; Zhang, Guo-zhi; Fu, Xue-bin; Himmelreich, Uwe; Oyen, Raymond; Verbruggen, Alfons; Ni, Yi-cheng

    2012-01-01

    Aim: Hypericin (Hyp) and its radio-derivatives have been investigated in animal models with ischemic heart diseases and malignancies for diagnostic and therapeutic purposes. Before radioiodinated Hyp (123I-Hyp or 131I-Hyp) can be considered as a clinically useful drug, vigorous evaluations on its chemotoxicity are necessary. In the present study, we examined the toxicity of a single dose of non-radioactive 127I-Hyp in normal mice for 24 h and 14 d. Methods: Studies were performed on 132 normal mice. 127I -Hyp at a clinically relevant dose of 0.1 mg/kg body weight and a 100-times higher dose of 10 mg/kg was intravenously injected into 40 mice. The safety aspects of clinical manifestations, serological biochemistry, and histopathology were assessed. In another 72 mice, 127I-Hyp was administered intravenously at assumed values to bracket the value of LD50. The rest 20 mice were used in the control groups. Results: At 24 h and 14 d following the injection of 127I -Hyp at either 0.1 or 10 mg/kg, all mice tolerated well without mortality or any observable treatment-related symptoms. No significant differences were found in blood biochemical parameters between the test and control groups. All organs presented normal appearances upon histopathological inspection. The value of LD50 of 127I-Hyp in mice through intravenous injection was 20.26 mg/kg, with the 95% confidence interval between 18.90 and 21.55 mg/kg. Conclusion: The current study reveals a broad safety range of 127I-Hyp, which not only supports the use of 123I-Hyp or 131I-Hyp in the necrosis targeting theragnostic strategy, but also serves as a valuable reference for exploring other possible applications for iodinated Hyp. PMID:23103619

  17. An animal model for the study of the genetic bases of behaviour in men: the multiple marker strains (MMS).

    PubMed

    Clment, Y; Lepicard, E; Chapouthier, G

    2001-06-01

    Animal models are often used for preclinical research on the neurobiology of psychiatric disorders. Whereas many are employed to screen new therapeutic agents, few of them are used to study the genetic bases of psychiatric diseases, probably because of the complex genetic determinism underlying quantitative behavioral traits such as mood, personality or intelligence. The present article presents a short review introducing an analysis model using mice: the marker strains model. Using this model it is possible both to display genetic determinism data and to locate some of the chromosomal fragments involved in the regulation of anxiogenic processes. At present it cannot accurately determine the position of one or more genes, but it does provide a valuable means of 'scanning' the genome for an approximation. Through genetic analysis, using the model, an attempt will be made to identify autosomal fragments which may be involved in two behavioural traits: anxiety and chemical-induced seizures. In this paper, after reviewing theoretical aspects of looking for genes involved in behaviour, we will successively introduce studies in genetic topics in psychiatric human studies as well as appropriated behavioural animal studies. Then we will present a genetic model in mice which allows us to locate chromosomal fragments associated with a behavioural trait: multiple marker strains. PMID:11418276

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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...

  8. 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

  9. 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

  10. 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…

  11. Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an animal study.

    PubMed

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Liu, Ching-Ru; Fang, Chia-Lang; Hu, Chung-Hong; Fang, Jia-You

    2006-10-27

    Topical delivery of antisense oligonucleotides (ASOs) and DNA is attractive for treatment of skin disorders. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The objective of this study was to enhance and optimize the skin absorption of gene-based drugs by an erbium:yttrium-aluminum-garnet (Er:YAG) laser. The animal model utilized nude mice. In the in vitro permeation study, the Er:YAG laser treatment produced a 3-30-fold increase in ASO permeation which was dependent on the laser fluence and ASO molecular mass used. The fluorescence microscopic images showed a more-significant localization of a 15-mer ASO in the epidermis and hair follicles after laser application as compared with the control. The expressions of reporter genes coding for beta-galactosidase and green fluorescent protein (GFP) in skin were assessed by X-gal staining and confocal laser scanning microscopy. The SC ablation effect and photomechanical waves produced by the Er:YAG laser resulted in DNA expression being extensively distributed from the epidermis to the subcutis. The GFP expression in 1.4 J/cm2-treated skin was 160-fold higher than that in intact skin. This non-invasive, well-controlled technique of using an Er:YAG laser for gene therapy provides an efficient strategy to deliver ASOs and DNA via the skin. PMID:17005286

  12. 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

  13. 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

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

    PubMed

    Diaz, Silvina Laura; Narboux-Nme, Nicolas; Boutourlinsky, Katia; Doly, Stphane; 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

  15. 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

  16. 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

  17. 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

  18. The ability of animal studies to detect serious post marketing adverse events is limited.

    PubMed

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

    2012-12-01

    The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia. PMID:22982732

  19. Carcinogenicity studies with medroxalol hydrochloride in rats and mice.

    PubMed

    Sells, D M; Gibson, J P

    1987-01-01

    The carcinogenic potential of medroxalol hydrochloride, an antihypertensive agent with beta 1 adrenergic cardiac blocking properties, and beta 2 and some alpha 1 vasodilating activity, was studied by dietary administration. Long Evans rats were treated for 2 years and CD-1 mice for 18 months at dosages of 0, 50, 250 or 500 mg/kg/day. Medroxalol did not produce any evidence of a tumorigenic effect in the Long Evans rat, but graying of pigmented hair was noted at 250 and 500 mg/kg/day and is probably related to melanin binding of the drug. In the CD-1 mouse, there was a dose related increase in uterine leiomyomas that was statistically significant (p less than 0.05) at doses of 250 and 500 mg/kg/day. The incidence at 50 mg/kg/day was not different from control. Endometrial stromal sarcomas were observed only in treated mice, and pairwise comparison with controls indicated a statistically significant difference (p less than 0.05) only at the lowest dosage (50 mg/kg/day). The latter finding may not be related to treatment since there was no dose response and the incidence in the two higher dose groups was neither statistically significant nor higher than occasionally seen in other control groups. PMID:3432947

  20. 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 (860 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

  1. 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.

  2. 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.

  3. Effect of chronic ethanol exposure on the hepatotoxicity of ecstasy in mice: an ex vivo study.

    PubMed

    Pontes, Helena; Santos-Marques, Maria Joo; Fernandes, Eduarda; Duarte, Jos Alberto; Remio, Fernando; Carvalho, Flix; Bastos, Maria Lourdes

    2008-06-01

    3,4-Methylenedioxymethamphetamine (MDMA) is frequently consumed at "rave" parties by polydrug users that usually take this drug in association with ethanol. In addition, many young people are repeatedly exposed to ethanol, which likely leads to tolerance phenomena. Both compounds are metabolized in the liver, with formation of hepatotoxic metabolites, which gives high relevance to the evaluation of their putative toxicological interaction. Therefore, the aim of this study was to evaluate the toxicity induced by 0.8 and 1.6 mM MDMA to freshly isolated hepatocytes obtained from ethanol-treated mice whose tap drinking water was replaced by a 5% ethanol solution for 1 week and, afterwards, by a 12% ethanol solution for 8 weeks (ethanol group) comparatively to non-treated animals (non-ethanol group). The hepatocytes were incubated under normothermic and hyperthermic conditions in order to simulate in vitro the hyperthermic response induced in vivo by MDMA, a condition that has been recognized as a life-threatening effect associated with MDMA exposure and implicated in its hepatotoxicity. Six mice treated under the same protocol as the ethanol group were used for histological analysis, and compared to non-ethanol-treated animals. The pre-treatment of mice with ethanol caused a significant decrease in the hepatocytes yield in the isolation procedure comparatively to the non-ethanol group, which can be explained by an increase in collagen deposition along the hepatic parenchyma as observed in the histological analysis. The initial cell viability of hepatocytes suspensions was similar between ethanol and non-ethanol groups. However, the ethanol group showed a higher GSH oxidation rate, which was enhanced under hyperthermia. Additionally, a concentration-dependent MDMA-induced loss of cell viability and ATP depletion was observed for both groups, at 41 degrees C. In conclusion, the repeated treatment with ethanol seems to increase the vulnerability of freshly isolated mice hepatocytes towards pro-oxidant conditions, as ascertained by the increase in collagen deposition, lower hepatocyte yield and decreased glutathione levels. However, MDMA toxicity to the isolated hepatocytes was independent of ethanol pre-treatment, while significantly dependent on incubation temperature. PMID:18325728

  4. 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...

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

    PubMed Central

    Borah, Mukundam; Sarma, Phulen; Das, Swarnamoni

    2014-01-01

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

  7. 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

  8. 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

  9. 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.

  10. Mortality and translocation assay to study the protective capacity of Bifidobacterium lactis INL1 against Salmonella Typhimurium infection in mice.

    PubMed

    Zacaras, M F; Reinheimer, J; Forzani, L; Grangette, C; Vinderola, G

    2014-12-01

    The mouse has been largely used for the study of the protective capacity of probiotics against intestinal infections caused by Salmonella. In this work we aimed at comparing the mortality and translocation assay for the study of the protective capacity of the human breast milk-derived strain Bifidobacterium animalis subsp. lactis INL1 on a model of gut infection by Salmonella enterica subsp. enterica serovar Typhimurium. Different doses of S. Typhimurium FUNED and B. animalis subsp. lactis INL 1 were administered to Balb/c mice in a mortality or a translocation assay. The survival of the control group in the mortality assay resulted to be variable along experiments, and then we preferred to use a translocation assay where the preventive administration of 109 cfu of bifidobacteria/mouse for 10 consecutive days significantly reduced the number of infected animals and the levels of translocation to liver and spleen, with enhanced secretory immunoglobulin A and interleukin 10 production in the small and large intestine, respectively. Ten days of B. animalis subsp. lactis strain INL1 administration to mice significantly reduced both the incidence and the severity of Salmonella infection in a mouse model of translocation. This work provided the first evidence that a translocation assay, compared to a mortality assay, could be more useful to study the protective capacity of probiotics against Salmonella infection, as more information can be obtained from mice and less suffering is conferred to animals due to the fact that the mortality assay is shorter than the latter. These facts are in line with the guidelines of animal research recently established by the National Centre for the Replacement, Refinement & Reduction of Animals in Research. PMID:24902954

  11. 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.

  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

    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 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. PMID:24387502

  14. Evaluating the dose effects of a longitudinal micro-CT study on pulmonary tissue in C57BL/6 mice

    NASA Astrophysics Data System (ADS)

    Detombe, Sarah A.; Dunmore-Buyze, Joy; Petrov, Ivailo E.; Drangova, Maria

    2012-03-01

    Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

  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. Animal Models of Diabetic Uropathy

    PubMed Central

    Daneshgari, Firouz; Leiter, Edward H.; Liu, Guiming; Reeder, Jay

    2015-01-01

    Purpose Diabetes mellitus (DM) is a group of debilitating and costly diseases with multiple serious complications. Lower urinary tract complications or Diabetic Uropathy (DU) are among the most common complications of DM, surpassing the widely recognized complications such as neuropathy and nephropathy1. DU develops in both type 1 and type 2 diabetic humans and very little is known about the natural history of these common and troublesome complications. Animal models have the potential to reveal mechanisms and aid in the development of treatment strategies. Methods We present a review of available animal models of DM relative to their use in the study of DU. Results Both large animal and small animal models of DM are available. While large animals such as dogs and swine may closely mirror the human disease in size and phenotype, the length of time between onset and development of diabetic complications and associated husbandry expenditures can make the acquisition of data from statistically valid sample sizes prohibitively expensive. In contrast small animal models (rats and mice) have much lower expenditures for larger numbers of animals, compressed observation time due to shorter lifespan and mice are readily manipulated genetically to facilitate the isolation of the effect of single genes (transgenic and knockout mice). Type 1 DM can be induced chemically using streptozotocin which is selectively toxic to pancreatic beta cells. Type 2 DM models have been developed by selective breeding for hyperglycemia with or without associated obesity. There are several well characterized and predictable animal models of DM in which the presence of DU has been demonstrated. Conclusions Diabetic Uropathy, including diabetic bladder dysfunction have been more frequently studied among small animals of type I diabetes. Recent availability of transgenic models provides a new opportunity for further studies of DU among mice models of both types I and II DM. PMID:19846143

  19. 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.

  20. 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

  1. 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

  2. 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

  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. 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...

  5. Applying stereotactic injection technique to study genetic effects on animal behaviors.

    PubMed

    McSweeney, Colleen; Mao, Yingwei

    2015-01-01

    Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors. PMID:25992973

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

    PubMed

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

    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. PMID:26502234

  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. 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

  10. 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…

  11. 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

  12. A quantitative study of cerebrovascular variation in inbred mice.

    PubMed Central

    Ward, R; Collins, R L; Tanguay, G; Miceli, D

    1990-01-01

    The arteries of the base of the mouse brain were examined after perfusion with India ink. A qualitative difference exists between inbred mice of three strains (C57BL/6J, 129/J and BALB/cCF) on the one hand, and genetically defined heterogeneous mice on the other; the latter consistently show anomalies similar to those previously described in genetically undefined rodents, whereas inbred mice do not. A quantitative morphometric analysis of the Circle of Willis of inbred mice was undertaken. The results of this analysis are consistent with the notion that the differences in shape between the circles of Willis of different strains of inbred mice are due to additive genetic variation between these strains. PMID:2074233

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Macher, Egon; Chase, Merrill W.

    1969-01-01

    In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 g of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 g and 5.0 g amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity. Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 g of picryl chloride (PCl) or at 12 hr after injection of 5.0 g of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsivenesssometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank. The allergen remaining in the ear after the early outflow, particularly between 1224 hr and 34 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable. The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independentlytolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue. PMID:5782765

  15. 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)

  16. Evaluation of anxiolytic activity of aqueous extract of Coriandrum sativum Linn. in mice: A preliminary experimental study

    PubMed Central

    Latha, K.; Rammohan, B.; Sunanda, B. P. V.; Maheswari, M. S. Uma; Mohan, Surapaneni Krishna

    2015-01-01

    Objectives: To evaluate the anxiolytic effect of Coriandrum sativum (CS) aqueous extract in mice. To compare the antianxiety activity of CS against standard drug diazepam (3 mg/kg). Materials and Methods: After obtaining Institutional Animal Ethics Committee approval, Swiss albino mice (1825 g) of either sex were randomly divided into five groups of six animals each. Dried powder of CS leaves was boiled with distilled water, cooled, filtered, placed on a hotplate for complete evaporation, finally weighed and stored. The control group, test group, and standard drugs group received saline, CS extract (50, 100, and 200 mg/kg), diazepam (3 mg/kg), respectively, by oral feeding. The antianxiety effect was assessed by elevated plus maze (EPM) in mice. Results: In EPM, it implied that CS 50 mg/kg (Group III), 100 mg/kg (Group IV), and 200 mg/kg (Group V) significantly (P < 0.001) increases the number of entries in open arms compared to control. The time spent in open arms also increased in all the doses of CS extract significantly. Conclusion: The current study demonstrates statistically significant dose-dependent antianxiety activity of CS leaves. PMID:26109787

  17. 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.

  18. Inhalation teratology studies of n-butyl mercaptan in rats and mice.

    PubMed

    Thomas, W C; Seckar, J A; Johnson, J T; Ulrich, C E; Klonne, D R; Schardein, J L; Kirwin, C J

    1987-02-01

    n-Butyl mercaptan (n-BM) is used as a solvent and a chemical intermediate. Pregnant Charles River CD-1 mice and COBS CD rats were randomly assigned to a control group and to three n-BM-exposed groups of 25 rats and 25 mice each. The animals were exposed by whole-body inhalation to mean n-BM concentrations of 10, 68, or 152 ppm on a 6-hr daily exposure schedule. Rats were exposed on Gestation Days 6-19 and mice on Gestation Days 6-16. The control group was exposed to filtered air only on a comparable regimen. Cesarean sections were performed on all surviving mice on Gestation Day 17 and on all rats on Gestation Day 20. Seventeen of the n-BM-treated mice died: 8 at the 68-ppm level and 9 at the 152-ppm level; none of the n-BM-treated rats died. An increased postimplantation loss and increased early resorption occurred in mice exposed at 68 and 152 ppm, indicating embryotoxicity. An increased incidence of cleft palate was observed in mice exposed to 10 or 68 ppm which was not statistically significant. Total fetal abnormalities were statistically significantly different from controls at 68 ppm where maternal lethality was observed when based on the fetal unit although not when based on the litter unit. Rats exposed to 152 ppm or less demonstrated no terata. PMID:3556829

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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).

  5. 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)

  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

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

    2015-03-01

    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. 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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-characterized animal model for predicting the response in humans; (3) The animal study endpoint is clearly... as part of their application a plan or approach to postmarketing study commitments in the event such... with special training or experience; (ii) Distribution conditioned on the performance of...

  12. 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…

  13. 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...

  14. 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

  15. Juvenile animal studies for the development of paediatric medicines: a description and conclusions from a European Medicines Agency workshop on juvenile animal testing for nonclinical assessors.

    PubMed

    Silva-Lima, Beatriz; Due Theilade-Thomsen, Mette; Carleer, Jacqueline; Vidal, Jean-Marc; Tomasi, Paolo; Saint-Raymond, Agnes

    2010-12-01

    A workshop organised by the European Medicines Agency involved assessors and experts present in a Nonclinical Working Group evaluating juvenile animal studies for Paediatric Investigation Plans in collaboration with the Paediatric Committee and the Safety Working Party of the Committee for Human Medicinal Products. The objective of the workshop was to analyse which juvenile animal studies proposals were received and agreed by the Paediatric Committee, to check consistency and how to apply the existing European guideline on juvenile animal studies. A comparison of main organ system development in man vs. animal species was presented to guide the review and to support species selection and protocol design. An analysis of juvenile animal studies included in finalised PIP's was also presented. Out of 109 paediatric investigation plans finalised between November 2008 and March 2009, 43 included one or more juvenile animal studies. In most cases the preferred species was the rat; one species only was requested to be studied (20/22), but in a minority two species were required (2/22). When deciding on the characteristics of the juvenile animal studies, such as age of animals at study start, the age of the children targeted by the medicine was considered. It is expected that the increasing experience gained by Applicants and Regulators will allow further refining the criteria for these juvenile animal studies. Further research on this topic is highly encouraged in the European Regulatory framework. PMID:20632393

  16. 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

  17. 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.

  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. 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

  20. 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

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

    PubMed

    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 ? 1-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 ? 1-receptor. PMID:26170874

  2. 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.

  3. Modeling the study of DNA damage responses in mice.

    PubMed

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

    2015-01-01

    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 aging. 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

  4. 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 ?1-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 ?1-receptor. PMID:26170874

  5. 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

  6. 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

  7. 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

  8. 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

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

    PubMed Central

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

  10. 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

  11. 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.

  12. [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; Afanasv, 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

  13. 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.

  14. 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

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

    PubMed Central

    2007-01-01

    Previous work has established that a narrated animation is more effective at communicating a complex biological process (signal transduction) than the equivalent graphic with figure legend. To my knowledge, no study has been done in any subject area on the effectiveness of animations versus graphics in the long-term retention of information, a primary and critical issue in studies of teaching and learning. In this study, involving 393 student responses, three different animations and two graphicsone with and one lacking a legendwere used to determine the long-term retention of information. The results show that students retain more information 21 d after viewing an animation without narration compared with an equivalent graphic whether or not that graphic had a legend. Students' comments provide additional insight into the value of animations in the pedagogical process, and suggestions for future work are proposed. PMID:17785404

  16. 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

  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. Talking about Animals: Studies of Young Children Visiting Zoos, a Museum and a Farm.

    ERIC Educational Resources Information Center

    Tunnicliffe, Susan Dale

    The purpose of this study was to identify the content and form of the conversations and recognize the variables that are acting during visits to animal exhibits, and the influence on conversational content of both different types of locations and animal exhibits and visit rationales. Conversations of children between the ages of 3 and 12 years and

  19. 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

  20. 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 ...

  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. 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

  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. 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.

  6. 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.

  7. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study

    PubMed Central

    Hendrikse, Jeffrey; Beckers, Linda; Paulin, Nicole; Van der Heiden, Kim; Braster, Quinte; Drechsler, Maik; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

    2015-01-01

    Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models. PMID:26492161

  8. 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

  9. Anatomopathological study in BALB/c mice brains experimentally infected with Toxoplasma gondii.

    PubMed

    Silva, Marcos Gontijo da; Lino Jr, Ruy de Souza; da Costa, Tatiane Luiza; Soares, Joanna D'Aac Herzog; do Amaral, Waldemar Naves; Avelino, Mariza Martins; de Castro, Ana Maria

    2008-02-01

    Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts. PMID:18553015

  10. 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.

  11. CYTOGENETIC STUDIES OF MICE EXPOSED TO STYRENE BY INHALATION

    EPA Science Inventory

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

  12. 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

  13. 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.

  14. 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

  15. [Animal experiment study of healing of the sutured flexor tendon].

    PubMed

    Martini, A K; Blimke, B

    1992-01-01

    The purpose of the present study was to determine whether tendons contain intrinsic cells capable of repair. To accomplish this, rabbit flexor tendons were exposed microsurgically, cut through, resutured and transferred as free transplant into the knee-joint. Immobilisation of the knee-joint will cause progressive formation of adhesions permitting neovascularisation of the transplant. Both is not observed when sutured flexor tendons were put in a knee articulation with full range of joint motion. Transmission electron micrography revealed up to 8 weeks after implantation vital cells and incidences of collagen neosynthesis independently whether adhesions existed or not. Histologically intrinsic repair was confirmed in mobile transplants and mainly initiated by cells of the visceral synovial sheet which form an anatomic-surgical unity with the tendon. In conclusion the importance of the synovial fluid for the tendon nutrition is underlined by the fact that an intrinsic healing of flexor tendon is possible without formation of adhesions. PMID:1582849

  16. 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

  17. 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

  18. Animal models of sepsis

    PubMed Central

    Fink, Mitchell P

    2014-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism. PMID:24022070

  19. Study of the Protective Effect of Teucrium polium L. Extract on Acetaminophen-Induced Hepatotoxicity in Mice

    PubMed Central

    Forouzandeh, Hossein; Azemi, Mohammad Ebrahim; Rashidi, Iran; Goudarzi, Mehdi; Kalantari, Heibatullah

    2013-01-01

    In the present study, protective effect of Teucrium polium L. (Labiatae) extract on acetaminophen-induced hepatotoxicity was investigated in mice. Animals were divided into six groups, each group consist of 8 mice. Group one as the negative control group received normal saline, while group two received only crude extract of T. polium L. (500 mg/Kg) for five days and group three as the positive group received acetaminophen (500 mg/Kg). Groups four, five and six received crude extract in doses of 125, 250 and 500 mg/Kg, respectively, and on the fifth day, one hour after the last administration, acetaminophen was given orally (500 mg/Kg). Then on the 6th day, animals were sacrificed, their blood was collected to determine serum enzyme activities of ALT, AST and ALP to measure the serum levels of directed and total bilirubin. The livers were removed for histological examination. The results of this study showed the protective effect in all doses but the most significant protection was observed in doses of 250 and 500 mg/Kg (p < 0.05). Also these findings were supported and confirmed by histological examination. PMID:24250580

  20. 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).

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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., invest

  6. 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.

  7. 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

  8. Numerical variation of dark cells in normal and chemically induced hyperplastic epidermis with age of animal and efficiency of tumor promoter. [Mice

    SciTech Connect

    Klein-Szanto, A.J.P.; Slaga, T.J.

    1981-11-01

    The percentage of dark basal keratinocytes was quantitatively assessed in normal epidermis of Sencar mice before and after birth and in adult epidermis after topical application of several compounds of varying promoting efficiency. The percentage of dark keratinocytes reached a maximum at the 19th day of gestation (approx.40%) and fell abruptly after birth (approx.3%). Old animals exhibited a very low number of dark basal cells (0.2%). After topical application of the weak promoters resiniferotoxin, anthralin, ethylphenylpropiolate, and 12-deoxyphorbol-13-2,4,6-decatrienoate, the percentage of dark cells in young adult epidermis did not differ markedly from that in control (acetone-treated) specimens. The strong first-stage promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and calcium ionophore A 23187, as well as the strong complete promoter 12-deoxyphorbol-13-deoxyphorbol-13-decanoate, induced the appearance of large numbers of dark keratinocytes, in a percentage similar to that seen after 12-O-tetra-decanoylphorbol-13-acetate application (approx.20%). The similarities between the dark keratinocytes seen after topical application of 12-O-tetradecanoylphorbol-13-acetate or other strong promoters and the dark cells observed in the fetal epidermis before the onset of the adult type of epidermal keratinization indicate that potent and/or first stage tumor promoters can be identified by their ability to induce cells resembling fetal-type dedifferentiated keratinocytes.

  9. 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

  10. 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

  11. Preclinical Evaluation of DMA, a Bisbenzimidazole, as Radioprotector: Toxicity, Pharmacokinetics, and Biodistribution Studies in Balb/c Mice.

    PubMed

    Nimesh, Hemlata; Tiwari, Vinod; Yang, Chunhua; Gundala, Sushma R; Chuttani, Krishna; Hazari, Puja P; Mishra, Anil K; Sharma, Abhisheak; Lal, Jawahar; Katyal, Anju; Aneja, Ritu; Tandon, Vibha

    2015-10-01

    Radiotherapy, a therapeutic modality of cancer treatment, nonselectively damages normal tissues as well as tumor tissues. The search is ongoing for therapeutic agents that selectively reduce radiation-induced normal tissue injury without reducing tumoricidal effect, thereby increasing the therapeutic ratio of radiation therapy. Our laboratory established 5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'benzimidazolyl] benzimidazole (DMA) as noncytotoxic radioprotector in mammalian cells. DMA showed an excellent radioprotection in mice at single nontoxic oral dose by a dose-reduction factor of 1.28. An oxygen radical absorbing capacity assay confirmed its free-radical quenching ability. Single bolus dose and 28-days of repeated administration of DMA in mice for toxicity studies determined an LD50 of >2000 mg/kg body weight (bw) and 225 mg/kg bw, respectively, suggesting DMA is safe. Histopathology, biochemical parameters, and relative organ weight analysis revealed insignificant changes in the DMA-treated animals. The pharmacokinetic study of DMA at oral and intravenous doses showed its C(max) = 1 hour, bioavailability of 8.84%, elimination half-life of 4 hours, and an enterohepatic recirculation. Biodistribution study in mice with Ehrlich ascites tumors showed that (99m)Tc-DMA achieved its highest concentration in 1 hour and was retained up to 4 hours in the lungs, liver, kidneys, and spleen, and in a low concentration in the tumor, a solicited property of any radioprotector to protect normal cells over cancerous cells. We observed that the single-dose treatment of tumor-bearing mice with DMA 2 hours before 8 Gy total body irradiation showed an impressive rescue of radiation-induced morbidity in terms of weight loss and mortality without a change in tumor response. PMID:26240287

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

    PubMed Central

    2011-01-01

    Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies. PMID:21835012

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

    PubMed

    Kransler, Kevin M

    2014-06-01

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

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

    PubMed

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

    2015-01-01

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

  15. 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

  16. Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged Mice: An Immunohistochemical Study

    PubMed Central

    Kim, Chan-Sik; Park, Sok; Chun, Yoonseok; Song, Wook; Kim, Hee-Jae; Kim, Junghyun

    2015-01-01

    In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control). Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks). The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML), 8-hydroxy-2?-deoxyguanosine (8-OHdG) and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress. PMID:26404251

  17. 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

  18. 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 Rodrguez; Estivill-Torrs, Guillermo; Santn, 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

  19. 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,

  20. 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,…

  1. 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

  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. 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.

  4. Predictive criteria to study the pathogenesis of malaria-associated ALI/ARDS in mice.

    PubMed

    Ortolan, Luana S; Sercundes, Michelle K; Barboza, Renato; Debone, Daniela; Murillo, Oscar; Hagen, Stefano C F; Russo, Momtchilo; D' Imprio Lima, Maria Regina; Alvarez, Jos M; Amaku, Marcos; 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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 (19962004) 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

  12. 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

  13. 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

  14. 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

  15. 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 (AECs), 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 Donabedians 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

  16. Ultra-high-resolution imaging of small animals: implications for preclinical and research studies.

    PubMed

    Weber, D A; Ivanovic, M

    1999-01-01

    Recent developments in the use of pinhole SPECT and dedicated PET for UHR small animal imaging have identified the technology that can be used to provide images with spatial resolution of the order of 1 to 3 mm. In SPECT imaging, rotating camera pinhole SPECT has provided the means to use existing equipment to achieve UHR images. It has the disadvantages of low sensitivity and requires special image software to reconstruct tomographic slices. However, with minimal additional cost to an imaging laboratory, pinhole SPECT can provide a quantitatively accurate imaging technique for small-animal studies. New detector technology offers considerable promise; however, more studies are required before any one system can be singled out as offering major advantages over the pinhole SPECT method for general purpose small-animal SPECT imaging. The search for the means to achieve better sensitivity with UHR continues. In PET imaging, with few exceptions, the general trend has been to design systems dedicated to small-animal imaging to achieve UHR images with satisfactory sensitivity for quantitative UHR imaging. Several of the ring configuration, small-animal PET imaging systems provide good sensitivity and high spatial resolution. The cost of many of these systems, however, is relatively high, and investigators continue to explore different detector materials and imaging geometries to develop an instrument with acceptable levels of sensitivity with UHR imaging capability. We believe that both small-animal SPECT and PET imaging techniques now offer practical UHR imaging methods for quantitative small-animal imaging. As these tools are implemented in the investigation of new radiopharmaceuticals, we expect the utility of in vivo small animal assays will support further research in optimizing this technology. PMID:10385189

  17. 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

  18. 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

  19. 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

  20. 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)

  1. 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

  2. On the Use of a Simple Physical System Analogy to Study Robustness Features in Animal Sciences.

    PubMed

    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

  3. 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

  4. 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

  5. Animal models to study acute and chronic intestinal inflammation in mammals.

    PubMed

    Jiminez, Janelle A; Uwiera, Trina C; Douglas Inglis, G; Uwiera, Richard R E

    2015-01-01

    Acute and chronic inflammatory diseases of the intestine impart a significant and negative impact on the health and well-being of human and non-human mammalian animals. Understanding the underlying mechanisms of inflammatory disease is mandatory to develop effective treatment and prevention strategies. As inflammatory disease etiologies are multifactorial, the use of appropriate animal models and associated metrics of disease are essential. In this regard, animal models used alone or in combination to study acute and chronic inflammatory disease of the mammalian intestine paired with commonly used inflammation-inducing agents are reviewed. This includes both chemical and biological incitants of inflammation, and both non-mammalian (i.e. nematodes, insects, and fish) and mammalian (i.e. rodents, rabbits, pigs, ruminants, dogs, and non-human primates) models of intestinal inflammation including germ-free, gnotobiotic, as well as surgical, and genetically modified animals. Importantly, chemical and biological incitants induce inflammation via a multitude of mechanisms, and intestinal inflammation and injury can vary greatly according to the incitant and animal model used, allowing studies to ascertain both long-term and short-term effects of inflammation. Thus, researchers and clinicians should be aware of the relative strengths and limitations of the various animal models used to study acute and chronic inflammatory diseases of the mammalian intestine, and the scope and relevance of outcomes achievable based on this knowledge. The ability to induce inflammation to mimic common human diseases is an important factor of a successful animal model, however other mechanisms of disease such as the amount of infective agent to induce disease, invasion mechanisms, and the effect various physiologic changes can have on inducing damage are also important features. In many cases, the use of multiple animal models in combination with both chemical and biological incitants is necessary to answer the specific question being addressed regarding intestinal disease. Some incitants can induce acute responses in certain animal models while others can be used to induce chronic responses; this review aims to illustrate the strengths and weaknesses in each animal model and to guide the choice of an appropriate acute or chronic incitant to facilitate intestinal disease. PMID:26561503

  6. Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats

    PubMed Central

    Sonabend, AM; Ulasov, IV; Han, Y; Rolle, CE; Nandi, S; Cao, D; Tyler, MA; Lesniak, MS

    2008-01-01

    Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH. PMID:19011597

  7. 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

  8. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

    PubMed

    Spengler, Jessica R; Bergeron, ric; 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

  9. 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

  10. 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

  11. Epidermal carcinogenesis studies of synthetic fossil fuel materials in mice.

    PubMed

    Renne, R A; Wright, C W; Smith, L G; Buschbom, R L

    1986-09-01

    Skin tumor response in mice to solvent fractions of heavy distillate (HD) from a solvent-refined coal (SRC-II) process indicated that the basic tar and neutral tar were the most carcinogenically potent fractions. Assays of another SRC-II coal liquid that had been fractionally distilled indicated that the carcinogenicity of this material for mouse skin is due to that portion boiling above 371 degrees C (700 degrees F), and that the carcinogenic potency of the material increased with boiling point. Samples of the 399-427 degrees C (750-800 degrees F) distillate were nitrosated to destroy primary aromatic amines and were chemically fractionated to assess the carcinogenicity of chemical class fractions of these complex mixtures. Data from these assays indicated that neutral polycyclic aromatic hydrocarbons (PAH) and nitrogen-containing polycyclic aromatic compounds (NPAC) both contribute to the carcinogenicity of this distillate. PMID:3750331

  12. NTP Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS No. 106-99-0) in B6C3F1 Mice (Inhalation Studies).

    PubMed

    1993-05-01

    1,3-Butadiene is produced in large volumes for use in the manufacture of synthetic rubber and of thermoplastic resins. In previous inhalation studies conducted by the NTP (NTP, 1984) there was clear evidence of multiple organ carcinogenicity in male and female mice exposed to 625 or 1,250 ppm 1,3-butadiene for 60 or 61 weeks. To better characterize exposure-response relationships for neoplasms and nonneoplastic lesions, toxicology and carcinogenesis studies were conducted by exposing groups of male and female B6C3F1 mice to air containing 1,3-butadiene (greater than 99% pure) for up to 2 years. An additional study in male B6C3F1 mice, in which exposure to 1,3-butadiene was stopped after limited exposure periods (13, 26, 40, or 52 weeks), was performed to assess the effects of varying concentration and duration of exposure on the incidences of 1,3-butadiene-induced neoplasms. In vitro genetic toxicology studies were conducted in Salmonella typhimurium and mouse lymphoma cells. In vivo genetic effects were assayed in germ cells of male Drosophila melanogaster and in bone marrow and peripheral blood cells of B6C3F1 mice. 2-Year Studies: Groups of 70 male and 70 female mice were exposed to air containing 0, 6.25, 20, 62.5, or 200 ppm 1,3-butadiene for 6 hours per day, 5 days per week for up to 2 years; groups of 90 male and 90 female mice were exposed to 625 ppm 1,3-butadiene on the same schedule. Up to 10 animals from each group were examined after 9 and 15 months of exposure. Survival and Body Weight in the 2-Year Studies: Two-year survival was decreased for males and females exposed to concentrations of 20 ppm or above, primarily due to the development of chemical-related malignant neoplasms. No female mice exposed to 200 or 625 ppm or males exposed to 625 ppm survived to the end of the studies (males: 35/50, 39/50, 24/50, 22/50, 4/50, 0/70; females: 37/50, 33/50, 24/50, 11/50, 0/50, 0/70). Mean body weights of exposed male and female mice were similar to those of the controls. Hematologic Effects in the 2-Year Studies: Hematologic parameters were evaluated after 9 and 15 months of exposure. At 9 months, decreases in erythrocyte counts, hemoglobin concentration, and packed red cell volume were observed in male mice exposed to 62.5 ppm or above and in female mice exposed to 200 or 625 ppm. Mean erythrocyte volume was increased in male mice exposed to 625 ppm and in females exposed to 200 or 625 ppm. At 15 months, decreases in erythrocyte counts, hemoglobin concentration, and packed red cell volume and increases in mean erythrocyte volume were observed in male and female mice exposed to 625 ppm. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Exposure of mice to 1,3-butadiene induced benign and malignant neoplasms at multiple sites. Statistically significant increases in the incidences of neoplasms at one or more sites were seen at concentrations of 20 ppm and higher in males and 6.25 ppm and higher in females. There was no exposure level in this study at which a significant carcinogenic response was not observed. Statistically significant increases occurred in the incidences of malignant lymphoma; histiocytic sarcoma; cardiac hemangiosarcoma; harderian gland adenoma; hepatocellular adenoma and carcinoma; alveolar/bronchiolar adenoma and carcinoma; mammary gland carcinoma, adenoacanthoma, and malignant mixed tumor (females only); benign and malignant ovarian granulosa cell tumor; and forestomach squamous cell papilloma and carcinoma. Low incidences of uncommon neoplasms also occurred in exposed male and female mice, including intestinal carcinomas in males, renal tubule adenomas in males and females, skin sarcomas (all types combined) in females, and Zymbal's gland adenomas and carcinomas in females. Lymphocytic lymphomas appeared as early as week 23 and were the principal cause of death of male and female mice exposed to 625 ppm 1,3-butadiene. The early and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm resulted in a reduced number of mice at risk for neoplasms developing laterg

  13. 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...

  14. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... studies in animals. 314.610 Section 314.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610...

  15. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... studies in animals. 314.610 Section 314.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610...

  16. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... studies in animals. 314.610 Section 314.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610...

  17. 21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... studies in animals. 314.610 Section 314.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible § 314.610...

  18. 21 CFR 601.91 - Approval based on evidence of effectiveness from studies in animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false 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...

  19. 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

  20. 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

  1. Practical method for radioactivity distribution analysis in small-animal PET cancer studies

    PubMed Central

    Slavine, Nikolai V.; Antich, Peter P.

    2008-01-01

    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

  2. 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

  3. Local and systemic effects of commonly used cutaneous agents: lifetime studies of 16 compounds in mice and rabbits.

    PubMed

    Stenbck, F

    1977-11-01

    A number of commonly used external agents were applied repeatedly on the skin of the mouse and rabbit. These chemicals, components of commercially available products included 4-hydroxyanisole, benzalkonium chloride, bromodeoxyuridine, iododeoxyuridine, 5-nitroacenaphthene, N-N-diethyltoluamide, hexachlorophene, para-aminobenzole acid, benzophenone, isopropylmyristate, pyrogallol, resorcinol and ethylhexanediol. Also tested were a commercial hairspray, a dandruff shampoo and an anti-dandruff agent. Local and systemic changes were studied and the tumour incidence compared with that of an effective carcinogen, 9,10-dimethylbenz(a)anthracene. The mice showed no local toxic changes or tumour formation and the systemic tumour incidence, i.e., tumours of the liver, lungs, lymphatic system and other organs, was similar to that of control animals. In rabbits, a number of proliferative, benign and malignant ear tumours were observed in the positive controls, thereby demonstrating the efficacy of this model. Local toxic changes were seen in benzalkonium- and hexachlorophene-treated animals, but no skin tumours. Four animals had uterine tumours. In addition, one lung and one kidney tumour, unrelated to the method of treatment, were seen. PMID:579553

  4. 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

  5. Pulmonary Abnormalities in Mice with Paracoccidioidomycosis: A Sequential Study Comparing High Resolution Computed Tomography and Pathologic Findings

    PubMed Central

    Hidalgo, Jos Miguel; de Oliveira Pascarelli, Bernardo Miguel; Patio, Jairo Hernando; Lenzi, Henrique Leonel; Restrepo, Angela; Cano, Luz Elena

    2010-01-01

    Background Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters. Methodology Male BALB/c mice were intranasally inoculated with 3106 Paracoccidioides brasiliensis (Pb) conidia (n?=?50) or PBS (n?=?50). HRCT was done every four weeks to determine pulmonary lesions, quantify lung density, reconstruct and quantify lung air structure. Lungs were also analyzed by histopathology and histomorphometry. Results Three different patterns of lesions were evidenced by HRCT and histopathology, as follows: nodular-diffuse, confluent and pseudo-tumoral. The lesions were mainly located around the hilus and affected more frequently the left lung. At the 4th week post-challenge HRCT showed that 80% of the Pb-infected mice had peri-bronchial consolidations associated with a significant increase in upper lung density when compared with controls, (?26325 vs. ?42210 HU, p<0.001). After the 8th and 12th weeks, consolidation had progressed involving also the middle regions. Histopathology revealed that consolidation as assessed by HRCT was equivalent histologically to a confluent granulomatous reaction, while nodules corresponded to individual compact granulomas. At the 16th week of infection, confluent granulomas formed pseudotumoral masses that obstructed large bronchi. Discrete focal fibrosis was visible gradually around granulomas, but this finding was only evident by histopathology. Conclusions/Significance This study demonstrated that conventional HRCT is a useful tool for evaluation and quantification of pulmonary damage occurring in experimental mouse PCM. The experimental design used decreases the need to sacrifice a large number of animals, and serves to monitor treatment efficacy by means of a more rational approach to the study of human lung disease. PMID:20614019

  6. Lifetime toxicity/carcinogenicity studies of FD & C Blue No. 1 (brilliant blue FCF) in rats and mice.

    PubMed

    Borzelleca, J F; Depukat, K; Hallagan, J B

    1990-04-01

    FD & C Blue No. 1 was fed to Charles River CD rats and CD-1 mice as a dietary admixture in lifetime toxicity/carcinogenicity studies. The rat study was conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at dietary concentrations of 0.0%, 0.0%, 0.1%, 1.0% or 2.0%. After randomly selecting the F1 animals, the lifetime phase was initiated at the same levels with 70 rats/sex/group, including two control groups. The maximum exposure times were 116 and 111 wk for males and females, respectively. The no-observed-adverse-effect levels are dietary concentrations of 2.0% for males (1072 mg/kg body weight/day), and 1.0% for females (631 mg/kg/day) based on a 15.0% decrease in terminal body weight and decreased survival in the high-dose females compared with the combined control groups. Charles River CD-1 mice (60/sex/group) were fed FD & C Blue No. 1 as a dietary admixture at levels of 0.0%, 0.0%, 0.5%, 1.5% or 5.0% in a lifetime toxicity/carcinogenicity study. The maximum exposure time was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse-effect level established in this study is a dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively. PMID:2358248

  7. 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

  8. Long term effects of monosodium glutamate on spermatogenesis following neonatal exposure in albino mice--a histological study.

    PubMed

    Das, R S; Ghosh, S K

    2010-09-01

    Monosodium glutamate (MSG), popularly known as Azinomoto has been in use since long as a flavour enhancing substance. Its widespread use has also earned it a bad name as hazardous for human health. It has been incriminated to cause wide range of effects comprising retinal degeneration, metabolic disorders, endocrinal disorders including reduced fertility rate in both male and female experimental mice and rats following neonatal exposure. However there are many contradicting views too regarding the above effects which have prompted us to undertake the present study. In our study seven newborns of Swiss Albino mice were injected subcutaneously with MSG (2 mg/gm ofbody wt. in a dilution 40 mg of per ml. of distilled water) on completion of 2nd, 4th, 6th, 8th and 10th day of life. Similar number of controls were injected with same volume of distilled water. Testes were obtained through dissection on completion of 75 days of life. 5 micron thick sections were cut, stained by H.E. and Heidenhain's Iron Haematoxylin and studied under light microscope. It was observed from the quantitative analysis of the seminiferous tubules that there was increase in the number of the pachytene stage of primary spermatocyte in the experimental group as compared to that of the control animals of corresponding age. PMID:21446362

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2012-11-01

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

  13. [(11)C]Raclopride binding in the striatum of minimally restrained and free-walking awake mice in a positron emission tomography study.

    PubMed

    Takuwa, Hiroyuki; Maeda, Jun; Ikoma, Yoko; Tokunaga, Masaki; Wakizaka, Hidekatsu; Uchida, Shouko; Kanno, Iwao; Taniguchi, Junko; Ito, Hiroshi; Higuchi, Makoto

    2015-12-01

    Anesthesia and restraint stress have profound impacts on brain functions, including neural activity and cerebrovascular function, possibly influencing functional and neurochemical positron emission tomography (PET) imaging data. For circumventing this effect, we developed an experimental system enabling PET imaging of free-walking awake mice with minimal restraints by fixing the head to a holder. The applicability of this system was investigated by performing PET imaging of D2 dopamine receptors with [(11)C]raclopride under the following three different conditions: (1) free-walking awake state; (2) 1.5% isoflurane anesthesia; and (3) whole-body restraint without anesthesia. [(11)C]raclopride binding potential (BP(ND)) values under isoflurane anesthesia and restrained awake state were significantly lower than under free-walking awake state (P?mice were significantly higher than those in free-walking awake mice (P?mice. METH-induced reduction of [(11)C]raclopride BP(ND) in anesthetized mice showed a trend to be less than that in free-walking awake mice, implying that pharmacological modulation of dopaminergic transmissions could be sensitively captured by PET imaging of free-walking awake mice. We concluded that our system is of utility as an in vivo assaying platform for studies of brain functions and neurotransmission elements in small animals, such as those modeling neuropsychiatric disorders. PMID:26360510

  14. 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

  15. The promise and dilemma of cannabinoid therapy: lessons from animal studies of bone disease

    PubMed Central

    Idris, Aymen I

    2012-01-01

    The endocannabinoid system plays an important role in numerous physiological processes and represents a potential drug target for diseases ranging from brain disorders to cancer. Recent preclinical studies implicated endocannabinoids and their receptors in the regulation of bone cell activity and in the pathogenesis of bone loss. Cells and intervening nerves in the skeleton express cannabinoid receptors and the machinery for the synthesis and breakdown of endocannabinoids. In healthy adult mice, pharmacological and genetic inactivation of the cannabinoid type 1 receptor (CB1) and putative cannabinoid receptor GPR55 (G protein-coupled receptor 55) inhibit osteoclastic bone resorption and increase bone mass, suggesting that both receptors have a negative role in early bone development. Although no distinct abnormalities in bone development were observed in healthy adult mice deficient in cannabinoid type 2 receptors (CB2), pharmacological blockage of this receptor was effective in suppressing bone loss associated with increased bone turnover, particularly in mouse models of osteoporosis, arthritis and osteolytic bone disease. In the aging skeleton, CB1 deficiency causes accelerated osteoporosis characterized mainly by a significant reduction in bone formation coupled to enhanced adipocyte accumulation in the bone marrow. A similar acceleration of bone loss was also reported in aging CB2-deficient mice but found to be associated with enhanced bone turnover. This perspective describes the role of cannabinoid ligands and their receptors in bone metabolism and highlights the promise and dilemma of therapeutic exploitation of the endocannabinoid system for treatment of bone disorders. PMID:24363927

  16. Preliminary study of metabolic radiotherapy with 188Re via small animal imaging

    NASA Astrophysics Data System (ADS)

    Antoccia, A.; Baldazzi, G.; Bello, M.; Bernardini, D.; Boccaccio, P.; Bollini, D.; de Notaristefani, F.; Garibaldi, F.; Hull, G.; Mazzi, U.; Moschini, G.; Muciaccio, A.; Navarria, F.-L.; Orsolini Cencelli, V.; Pancaldi, G.; Pani, R.; Perrotta, A.; Riondato, M.; Rosato, A.; Sgura, A.; Tanzarella, C.; Uzunov, N.; Zuffa, M.

    2006-01-01

    188Re is a ? ( Emax=2.12 MeV) and ? (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, 99 mTc, molecules of hyaluronic acid (HA) have been labelled with 188Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.60.610 mm pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of 188Re and with C57 black mice injected with the 188Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at 90 degrees. They use a CsI(Tl) matrix with 115 mm pixels read out by H8500 Hamamatsu Flat panel PMT.

  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; Maa, 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 ?3 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. 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

  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. 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.

  1. 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

  2. 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 inh