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Sample records for mouse rat dog

  1. Chromosome preparations from microplate cultures of man, dog, rat, and mouse

    NARCIS (Netherlands)

    de Jong, B; Anders, GJPA; van der Meer, Ingrid H

    1976-01-01

    A simple method for making chromosomal preparations from 105 leukocytes from man, dog, mouse, and rat and from 0.01 ml total human and dog blood is developed. The leukocytes and the peripheral blood are cultured in Cooke microtiter plates in a culture volume of 0.1 ml. The culture medium is R.P.M.I.

  2. Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.

    Science.gov (United States)

    Chen, Huadong; Soroka, Dominique; Zhu, Yingdong; Sang, Shengmin

    2013-05-01

    There are limited data on the metabolism of [6]-shogaol (6S), a major bioactive component of ginger. This study demonstrates metabolism of 6S in liver microsomes from mouse, rat, dog, monkey, and human. The in vitro metabolism of 6S was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with 6S, three major reductive metabolites 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E,4E)-1-(4'-hydroxy-3'-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4'-hydroxy-3'-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis-Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites, M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than 6S. We conclude that 6S is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning preclinical trials toward 6S chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Prediction of Deoxypodophyllotoxin Disposition in Mouse, Rat, Monkey and Dog by Physiologically-based Pharmacokinetic Model and the Extrapolation to Human

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2016-12-01

    Full Text Available Deoxypodophyllotoxin (DPT is a potential anti-tumor candidate prior to its clinical phase. The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK model consisting of 13 tissue compartments to predict DPT disposition in mouse, rat, monkey and dog based on in vitro and in silico inputs. Since large interspecies difference was found in unbound fraction of DPT in plasma, we assumed that Kt:pl,u (unbound tissue-to-plasma concentration ratio was identical across species. The predictions of our model were then validated by in vivo data of corresponding preclinical species, along with visual predictive checks. Reasonable matches were found between observed and predicted plasma concentrations and pharmacokinetic parameters in all four animal species. The prediction in the related seven tissues of mouse was also desirable. We also attempted to predict human pharmacokinetic profile by both the developed PBPK model and interspecies allometric scaling across mouse, rat and monkey, while dog was excluded from the scaling. The two approaches reached similar results. We hope the study will help in the efficacy and safety assessment of DPT in future clinical studies and provide a reference to the preclinical screening of similar compounds by PBPK model.

  4. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

    Science.gov (United States)

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2016-08-05

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

  5. Metabolism of methylphenidate in dog and rat

    International Nuclear Information System (INIS)

    Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

    1981-01-01

    The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

  6. Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes.

    Science.gov (United States)

    Jeong, Hyeon-Uk; Kim, Ju-Hyun; Kong, Tae Yeon; Choi, Won Gu; Lee, Hye Suk

    2016-04-01

    Honokiol has antitumor, antioxidative, anti-inflammatory, and antithrombotic effects. Here we aimed to identify the metabolic profile of honokiol in mouse, rat, dog, monkey, and human hepatocytes and to characterize the enzymes responsible for the glucuronidation and sulfation of honokiol. Honokiol had a high hepatic extraction ratio in all five species, indicating that it was extensively metabolized. A total of 32 metabolites, including 17 common and 15 different metabolites, produced via glucuronidation, sulfation, and oxidation of honokiol allyl groups were tentatively identified using liquid chromatography-high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-2'-glucuronide) was the predominant metabolic pathway in hepatocytes of all five species; however, interspecies differences between 4- and 2'-glucuronidation of honokiol were observed. UGT1A1, 1A8, 1A9, 2B15, and 2B17 played major roles in M8 formation, whereas UGT1A7 and 1A9 played major roles in M9 formation. Human cDNA-expressed SULT1C4 played a major role in M10 formation (honokiol-2'-sulfate), whereas SULT1A1*1, 1A1*2, and 1A2 played major roles in M11 formation (honokiol-4-sulfate). In conclusion, honokiol metabolism showed interspecies differences.

  7. Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

    2017-04-01

    Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

  8. Effect of dog food containing 460 ppm fluoride on rat reproduction.

    Science.gov (United States)

    Marks, T A; Schellenberg, D; Metzler, C M; Oostveen, J; Morey, M J

    1984-01-01

    A one-generation, two-litter rat reproduction study was done in a kennel in Allegan County, Michigan, as part of an investigation of reproductive problems in Shetland sheepdogs (shelties). Since 1970, at least 115 sheltie litters at this kennel have been grossly deformed and/or have died, generally within 3 d of birth. The causative factor(s) appears to be associated with the environment, as the shelties have had successful pregnancies elsewhere. There was some concern that a potential threat to human reproduction also might exist in this area. After it was discovered that fluoride in the dog food had apparently caused mottled teeth and bony exostoses in dogs at this and at least two other kennels, dog-food fluoride content and local well water were investigated as possible causes of the reproductive problems. A two-way factorial statistical design allowed assessment of dietary fluoride content and water source and interaction between the two. UPj:TUC(SD)spf rats, 9 males and 18 females in each group, were assigned to treatment with high-fluoride dog food (460 ppm) and well water; high-fluoride dog food and distilled water; low-fluoride dog food (56 ppm) and well water; and low-fluoride dog food and distilled water. After 60 d in the kennel, the rats were mated. Even after two litters, the only adverse effect was dental fluorosis in the high-fluoride groups. The results indicated that rats cannot be used in the search for the cause(s) of reproductive problems in dogs in this kennel.

  9. Toxicity of hydroxyurea in rats and dogs.

    Science.gov (United States)

    Morton, Daniel; Reed, Lori; Huang, Wenhu; Marcek, John M; Austin-LaFrance, Robert; Northcott, Carrie A; Schelling, Scott H; Enerson, Bradley E; Tomlinson, Lindsay

    2015-06-01

    The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr. © 2014 by The Author(s).

  10. Comparison of plutonium systemic distribution in rats and dogs with published data in humans.

    Science.gov (United States)

    Melo, Dunstana R; Weber, Waylon; Doyle-Eisele, Melanie; Guilmette, Raymond A

    2014-11-01

    This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.

  11. Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

    NARCIS (Netherlands)

    van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

    2007-01-01

    Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

  12. Microscopic dose distribution around PuO2 particles in lungs of hamsters, rats and dogs

    International Nuclear Information System (INIS)

    Diel, J.H.; Mewhinney, J.A.; Guilmette, R.A.

    1982-01-01

    Syrian hamsters, Fischer-344 rats and Beagle dogs inhaled monodisperse aerosols of PuO 2 and were sacrificed 1 to 16 days after exposure. The microscopic distribution of dose and tissue-at-risk around individual particles in lung was studied using autoradiographs of the lungs. The dose pattern in dogs and rats was more diffuse than in hamsters, resulting in a calculation of about twice the tumor incidence in rats and dogs as in hamsters on the basis of dose pattern using the same dose-effect model for all three species. The tumorigenic effect of inhaled insoluble PuO 2 particles depends on the species inhaling the material; Syrian hamsters are much less susceptible than are rats or dogs. It has been suggested that a difference in dose distribution resulting from differences in particle distributions in the two species may contribute to the differences in susceptibility in Syrian hamsters and rats. The role of dose distribution in lung cancer production is explored in this study by measuring microscopic dose patterns in regions surrounding single PuO 2 particles in lung. The alveolar structures of the dog and rat are different than those of the hamster. Based on these measurements, particles of PuO 2 in lung are more likely to cause lung cancer in dogs and rats than in hamsters

  13. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    International Nuclear Information System (INIS)

    Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

    2013-01-01

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  14. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Turowska, Agnieszka [sterna biologicals GmbH and Co. KG, Marburg (Germany); Librizzi, Damiano [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Baumgartl, Nadja [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Kuhlmann, Jens; Dicke, Tanja [sterna biologicals GmbH and Co. KG, Marburg (Germany); Merkel, Olivia [Department of Pharmaceutical Sciences, Wayne State University, Detroit (United States); Homburg, Ursula [sterna biologicals GmbH and Co. KG, Marburg (Germany); Höffken, Helmut [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Renz, Harald [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Garn, Holger, E-mail: garn@staff.uni-marburg.de [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany)

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  15. Comparison of Pu metabolism and pulmonary tumors in dogs and rats exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Dagle, G.E.; Park, J.F.

    The dose-effect relationships of dogs and rats exposed by inhalation to 239 PuO 2 were compared to evaluate parameters that may provide a better understanding for extrapolating these laboratory animal results to humans. Comparisons were made on animals with lifetime lung doses between 1400 and 11,000 rad. Parameters compared included survival; Pu clearance and translocation; and time of occurrence, incidence and histopathology of pulmonary tumors. The group means for lifetime dose to lung were not significantly different between dogs and rats, but when survival time was expressed as the percentage of maximum life expectancy (MLE), the mean survival time of dogs was 40% of MLE and of rats was 56% of MLE. Lung tumors were the causes of death in 84% of the dogs and 54% of the rats; the mean survival time to lung tumor was 44% of MLE for dogs, compared to 57% of MLE for rats. Whole-body clearance of plutonium was slower in dogs. More Pu translocated to the thoracic lymph nodes, liver, and skeleton in the dogs than in rats. Estimates of species differences in lung clearance were dependent on the methods of estimating initial lung burden. There were parameters with qualitative and quantitative similarities in dogs and rats. Quantitative differences between species, generally within a factor of two, suggested that more reliable dosimetry estimates are needed to make quantitative extrapolation between species

  16. Comparative metabonomics of differential hydrazine toxicity in the rat and mouse

    International Nuclear Information System (INIS)

    Bollard, Mary E.; Keun, Hector C.; Beckonert, Olaf; Ebbels, Tim M.D.; Antti, Henrik; Nicholls, Andrew W.; Shockcor, John P.; Cantor, Glenn H.; Stevens, Greg; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.

    2005-01-01

    Interspecies variation between rats and mice has been studied for hydrazine toxicity using a novel metabonomics approach. Hydrazine hydrochloride was administered to male Sprague-Dawley rats (30 mg/kg, n = 10 and 90 mg/kg, n = 10) and male B6C3F mice (100 mg/kg, n = 8 and 250 mg/kg, n = 8) by oral gavage. In each species, the high dose was selected to produce the major histopathologic effect, hepatocellular lipid accumulation. Urine samples were collected at sequential time points up to 168 h post dose and analyzed by 1 H NMR spectroscopy. The metabolites of hydrazine, namely diacetyl hydrazine and 1,4,5,6-tetrahydro-6-oxo-3-pyridazine carboxylic acid (THOPC), were detected in both the rat and mouse urine samples. Monoacetyl hydrazine was detected only in urine samples from the rat and its absence in the urine of the mouse was attributed to a higher activity of N-acetyl transferases in the mouse compared with the rat. Differential metabolic effects observed between the two species included elevated urinary β-alanine, 3-D-hydroxybutyrate, citrulline, N-acetylcitrulline, and reduced trimethylamine-N-oxide excretion unique to the rat. Metabolic principal component (PC) trajectories highlighted the greater degree of toxic response in the rat. A data scaling method, scaled to maximum aligned and reduced trajectories (SMART) analysis, was used to remove the differences between the metabolic starting positions of the rat and mouse and varying magnitudes of effect, to facilitate comparison of the response geometries between the rat and mouse. Mice followed 'biphasic' open PC trajectories, with incomplete recovery 7 days after dosing, whereas rats followed closed 'hairpin' time profiles, indicating functional reversibility. The greater magnitude of metabolic effects observed in the rat was supported by the more pronounced effect on liver pathology in the rat when compared with the mouse

  17. Comparison of rats and dogs exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Park, J.F.; Dagle, G.E.

    1979-01-01

    Rats and dogs inhaled aerosols of 239 PuO 2 at comparable ages relative to their lifespan. Both received a single exposure. The estimated lung doses at death in dogs were between 1100 and 11,000 rad. From two inhalation experiments, rats receiving doses in this range were chosen from the high-level exposed animals for comparison. Based on this data base, several comparisons were investigated. Metabolism of the material was compared for all animals and for animals which developed lung tumors. The differences in histopathology and tumor incidence in the lung were also reviewed. Although there were several differences between species, there were also many similarities. On-going research in dogs should produce data which will allow clarification of these relationships

  18. Automated whole-genome multiple alignment of rat, mouse, and human

    Energy Technology Data Exchange (ETDEWEB)

    Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna

    2004-07-04

    We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

  19. Comparison of metabolism and late effects in dogs and rats exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Park, J.F.; Dagle, G.E.

    1980-01-01

    Lung tumors were observed proportionally earlier in relation to expected life span in dogs than in rats after inhalation of 239 PuO 2 . Dogs appear to translocate a higher percentage of initial lung burden to liver, skeleton and thoracic lymph nodes than rats

  20. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans

    1990-01-01

    for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we......Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did...... not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...

  1. The absorption of p-toluenediamine by the skin of rats and dogs

    International Nuclear Information System (INIS)

    Hruby, R.

    1977-01-01

    The cutaneous absorption of p-[Me- 14 C]toluenediamine, applied in formulations similar to those normally used for hair dyeing, was investigated in rats and dogs. When rat skin was exposed for 30 min to two different formulations, about 0.2% of the administered amount of p-toluenediamine was absorbed in each case. Excretion of the absorbed substance took place predominantly in the urine. At the end of the 24-hr experiment, a residue of 5.2 to 9.3% of the dose was found in the treated area of rat skin. Experiments with oral and subcutaneous application to the rat also demonstrated rapid elimination of the toluenediamine. Dog skin was exposed to one formulation containing p-toluenediamine for 3 hr. It is estimated that about 0.13% of the administered p-toluenediamine was absorbed. (author)

  2. The metabolism of the anti-inflammatory drug eterylate in rat, dog and man.

    Science.gov (United States)

    Wood, S G; John, B A; Chasseaud, L F; Johnstone, I; Biggs, S R; Hawkins, D R; Priego, J G; Darragh, A; Lambe, R F

    1983-12-01

    Oral doses of 14C-eterylate were well absorbed by rat and man and excreted mainly in the urine (94% dose by rat in three days and 91% by man in five days). Oral doses to dogs were excreted in similar proportions in both the urine and faeces, although faecal 14C was probably derived in part, from biliary-excreted material. Peak plasma 14C and drug concn. were generally reached between one and three hours after oral doses. In humans, only two metabolites, salicylic acid and 4-acetamido-phenoxyacetic acid, were detected in plasma. The latter was cleared more rapidly than the former and hence plasma salicyclate concn. reached a peak (10.9 and 19.8 micrograms/ml in Subjects 1 and 2, respectively) and initially declined with a half-life of about two-three hours. Plasma 4-acetamidophenoxyacetic acid concn. reached a peak (4.3, 10.0 micrograms/ml, respectively) and declined with a half-life of about one hour. Tissue concn. of 14C were generally greater in dogs than in rats. Highest conc. occurred at three hours in dogs and at one hour in rats. Apart from those in the liver and kidneys, tissue concn. were lower than those in the corresponding plasma. Unchanged drug was not detected in urine or plasma of any species and was rapidly metabolized in human plasma. The major 14C components in human urine were identified as salicyluric acid and 4-acetamidophenoxyacetic acid; minor metabolites were salicylic acid, gentisic acid and paracetamol. These metabolites were also detected in rat urine albeit in different proportions to those in human urine. Dog urine contained less of these metabolites and a major proportion of the 14C was associated with relatively non-polar components. Although salicylic acid and 4-acetamidophenoxyacetic acid were the only major circulating metabolites in man and rat, dog plasma also contained the non-polar urine metabolites.

  3. Stimultion by angiotensin of prostacyclin biosynthesis in rats and dogs.

    Science.gov (United States)

    Dusting, G J; Mullins, E M

    1980-01-01

    1. Stimulation of prostanoid release by angiotensins (AI and AII) in rat isolated mesenteric vasculature and in the circulation of anaesthetized dogs has been investigated by bioassay. 2. AI and AII released a PGI2-like substance into rat mesenteric effluent and arterial blood of dogs; PGE2, PGF2 alpha, or TXA2 were not detected. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captorpril. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captopril. 4. Intravenous AII (0.02-1.0 microgram kg-1min-1) in dogs released PGI2 mainly from the lungs since right atrial blood contained much less than arterial blood. 5. Indomethacin (1 microgram/ml) abolished AII-induced PGI2 release from the memestery preparation, but intravenous idomethacin (10 mg/kg), meclofenamate (2 mg/kg) or aspirin (100 mg/kg) did not eliminate the pulmonary source of PGI2 in dogs. These findings highlight the dangers of assuming in vivo treatment with cyclo-oxygenase inhibitors abolished biosynthesis of all prostanoids.

  4. Urinary Excretion of N-Nitroso Compounds in Rats Fed Sodium Nitrite and/or Hot Dogs

    Science.gov (United States)

    2015-01-01

    Nitrite-treated meat is a reported risk factor for colon cancer. Mice that ingested sodium nitrite (NaNO2) or hot dogs (a nitrite-treated product) showed increased fecal excretion of apparent N-nitroso compounds (ANC). Here, we investigated for the first time whether rats excrete increased amounts of ANC in their urine after they are fed NaNO2 and/or hot dogs. Rats were treated for 7 days with NaNO2 in drinking water or were fed hot dogs. Their 24 h urine samples were analyzed for ANC by thermal energy analysis on days 1–4 after nitrite or hot dog treatment was stopped. For two rats fed 480 mg NaNO2/L drinking water, mean urinary ANC excretion on days 1–4 was 30, 5.2, 2.5, and 0.8 nmol/day, respectively. For two to eight rats/dose given varied NaNO2 doses, mean urinary ANC output on day 1 increased from 0.9 (for no nitrite) to 37 (for 1000 mg NaNO2/L drinking water) nmol ANC/day. Urine samples of four rats fed 40–60% hot dogs contained 12–13 nmol ANC on day 1. Linear regression analysis showed highly significant correlations between urinary ANC excretion on day 1 after stopping treatment and varied (a) NaNO2 level in drinking water for rats fed semipurified or commercials diet and (b) hot dog levels in the diet. Some correlations remained significant up to 4 days after nitrite treatment was stopped. Urinary output of ANC precursors (compounds that yield ANC after mild nitrosation) for rats fed semipurified or commercial diet was 11–17 or 23–48 μmol/day, respectively. Nitrosothiols and iron nitrosyls were not detected in urinary ANC and ANCP. Excretion of urinary ANC was about 60% of fecal ANC excretion for 1 to 2 days after NaNO2 was fed. Administered NaNO2 was not excreted unchanged in rat urine. We conclude that urinary ANC excretion in humans could usefully be surveyed to indicate exposure to N-nitroso compounds. PMID:25183213

  5. Differences in both glycosylation and binding properties between rat and mouse liver prolactin receptors.

    Science.gov (United States)

    Lascols, O; Cherqui, G; Munier, A; Picard, J; Capeau, J

    1994-05-01

    To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.

  6. Biotransformation of a novel antimitotic agent, I-387, by mouse, rat, dog, monkey, and human liver microsomes and in vivo pharmacokinetics in mice.

    Science.gov (United States)

    Ahn, Sunjoo; Kearbey, Jeffrey D; Li, Chien-Ming; Duke, Charles B; Miller, Duane D; Dalton, James T

    2011-04-01

    3-(1H-Indol-2-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone (I-387) is a novel indole compound with antitubulin action and potent antitumor activity in various preclinical models. I-387 avoids drug resistance mediated by P-glycoprotein and showed less neurotoxicity than vinca alkaloids during in vivo studies. We examined the pharmacokinetics and metabolism of I-387 in mice as a component of our preclinical development of this compound and continued interest in structure-activity relationships for antitubulin agents. After a 1 mg/kg intravenous dose, noncompartmental pharmacokinetic analysis in plasma showed that clearance (CL), volume of distribution at steady state (Vd(ss)), and terminal half-life (t(1/2)) of I-387 were 27 ml per min/kg, 5.3 l/kg, and 7 h, respectively. In the in vitro metabolic stability study, half-lives of I-387 were between 10 and 54 min by mouse, rat, dog, monkey, and human liver microsomes in the presence of NADPH, demonstrating interspecies variability. I-387 was most stable in rat liver microsomes and degraded quickly in monkey liver microsomes. Liquid chromatography-tandem mass spectrometry was used to identify phase I metabolites. Hydroxylation, reduction of a ketone group, and O-demethylation were the major metabolites formed by the liver microsomes of the five species. The carbonyl group of I-387 was reduced and identified as the most labile site in human liver microsomes. The results of these drug metabolism and pharmacokinetic studies provide the foundation for future structural modification of this pharmacophore to improve stability of drugs with potent anticancer effects in cancer patients.

  7. Metabolism, excretion, and pharmacokinetics of S-allyl-L-cysteine in rats and dogs.

    Science.gov (United States)

    Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji; Kodera, Yukihiro

    2015-05-01

    The metabolism, excretion, and pharmacokinetics of S-allyl-l-cysteine (SAC), an active key component of garlic supplements, were examined in rats and dogs. A single dose of SAC was administered orally or i.v. to rats (5 mg/kg) and dogs (2 mg/kg). SAC was well absorbed (bioavailability >90%) and its four metabolites-N-acetyl-S-allyl-l-cysteine (NAc-SAC), N-acetyl-S-allyl-l-cysteine sulfoxide (NAc-SACS), S-allyl-l-cysteine sulfoxide (SACS), and l-γ-glutamyl-S-allyl-l-cysteine-were identified in the plasma and/or urine. Renal clearance values (l/h/kg) of SAC indicated its extensive renal reabsorption, which contributed to the long elimination half-life of SAC, especially in dogs (12 hours). The metabolism of SAC to NAc-SAC, principal metabolite of SAC, was studied in vitro and in vivo. Liver and kidney S9 fractions of rats and dogs catalyzed both N-acetylation of SAC and deacetylation of NAc-SAC. After i.v. administration of NAc-SAC, SAC appeared in the plasma and its concentration declined in parallel with that of NAc-SAC. These results suggest that the rate and extent of the formation of NAc-SAC are determined by the N-acetylation and deacetylation activities of liver and kidney. Also, NAc-SACS was detected in the plasma after i.v. administration of either NAc-SAC or SACS, suggesting that NAc-SACS could be formed via both N-acetylation of SACS and S-oxidation of NAc-SAC. In conclusion, this study demonstrated that the pharmacokinetics of SAC in rats and dogs is characterized by its high oral bioavailability, N-acetylation and S-oxidation metabolism, and extensive renal reabsorption, indicating the critical roles of liver and kidney in the elimination of SAC. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. The pharmacokinetics of a new benzamide drug clebopride, in the rat and the dog.

    Science.gov (United States)

    Segura, J; García, I; Borja, L; Tarrús, E; Bakke, O M

    1981-04-01

    After intravenous, intramuscular and oral administration of clebopride in the rat and the dog its apparent volume of distribution is high (1.6-3.2 1 kg-1) and it has a longer biological half-life than metoclopramide in both species. High clearance values and concentrations of metabolites in plasma after oral administration indicate that the drug is subjected to an extensive first pass metabolism in the rat. Thus, clebopride administered orally gives relatively low concentrations in the systemic circulation in rats even though it is rapidly absorbed. The metabolic processes appear to become saturated at high doses which is reflected in dose-dependent kinetics. Linear kinetics were observed in the dog, although enterohepatic recycling could occur.

  9. Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of plutonium from the rat

    International Nuclear Information System (INIS)

    Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

    1976-01-01

    After inhaling 1 to 4 HD (human dose equivalents, i.e. 1g of calcium trisodium N,N-bis(2-bis (carboxymethyl) amino ethyl)glycinate per 70kg of body weight) of Ca-DTPA, rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrified later than 3 weeks after the last exposure. Dogs were anesthetized and administered Ca-DTPA aerosols via an intratracheal catheter for 30min/day for 5 days. The average dose/exposure was 4 HD. One week after the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks post-exposure. Ephitheleal atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. In long-term studies, rats were administered a lung burden of about 78 nCi 239 Pu(NO 3 ) 4 by inhalation and 20 days later were given six inhalation treatments of about 1 HD Ca-DTPA. Over their lifetime these animals showed no difference in survival or bone or lung tumour incidence from rats receiving Pu alone. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months after the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed. (author)

  10. Absorption of transuranic nitrates by rats, guinea pigs, and dogs

    International Nuclear Information System (INIS)

    Sullivan, M.F.

    1978-01-01

    Absorption of 238 Pu and 241 Am from the gstrointestinal tract was found to be quite similar for rats, guinea pigs, and dogs. Different oxidation state mixtures of 238 Pu nitrate (95% versus 65% Pu IV) were absorbed to about the same extent

  11. Changes in the electrocardiograms of rats and dogs exposed to dc magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Gaffey, C.T.; Tenforde, T.S.

    1979-03-01

    An evaluation of cardiovascular performance in magnetic fields (MF) is being undertaken. Cardiovascular performance is evaluated as a function of the MF strength. Since the vector characteristics of MF may be a factor influencing cardiovascular function, the positional arrangement of animals in a MF is being tested. In practice, each test animal is inserted between the poles of a magnet in a selected orientation that locates the heart in the center of the MF. The electrocardogram (ECG) is recorded before, during, and following the application of a MF. The interval between summits of the R waves allows the average heart rate to be obtained. The average respiratory rate is measured from the baseline shifts in the ECG trace. The major change in the ECG pattern induced by a MF is an increase in the amplitude of the T wave of rats and dogs. In our rat study a 20,000 gauss field increased the T wave by about 450%; the dog's T wave was increased 750% by a 16,000 gauss field. These biomagnetic effects appear to be reversible. Out experiments with rats and dogs were designed to test for the presence of a magnetic strength threshold (MST) to evoke T wave enhancement. The MST is defined as the minimum number of gauss to product a measurable change with T wave amplitude. The MTS is 3.0 kgauss for rats and 0.9 kgauss for dogs. Augmentation of the T wave was found to be greatest when thelines of the MF were perpendicular to the long axis of the body and least when parallel. Hence, the orientation of the subject in the MF influences the ECG profile.

  12. The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents.

    Science.gov (United States)

    Haitina, Tatjana; Fredriksson, Robert; Foord, Steven M; Schiöth, Helgi B; Gloriam, David E

    2009-01-15

    The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

  13. The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents

    Directory of Open Access Journals (Sweden)

    Schiöth Helgi B

    2009-01-01

    Full Text Available Abstract Background The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. Results We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. Conclusion The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

  14. MMB4 DMS: cardiovascular and pulmonary effects on dogs and neurobehavioral effects on rats.

    Science.gov (United States)

    Roche, Brian M; Vinci, Tom M; Hawk, Michael A; Hassler, Craig R; Pressburger, David T; Osheroff, Merrill R; Ritchie, Glenn D; Burback, Brian L

    2013-01-01

    The objectives of these studies were to determine the cardiopulmonary effects of a single intramuscular administration of 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) on dogs and on the central nervous system in rats. On days 1, 8, 15, and 22, male and female dogs received either vehicle (water for injection/0.5% benzyl alcohol/methane sulfonic acid) or MMB4 DMS (20, 50, or 100 mg/kg). Pulmonary function was evaluated for the first 5 hours after concurrent dosing with cardiovascular monitoring; then cardiovascular monitoring continued for 72 hours after dosing. Rats were dosed once by intramuscular injection with vehicle (water for injection/0.5% benzyl alcohol/methane sulfonic acid) or MMB4 DMS (60, 170, or 340 mg/kg). In dogs, 100 mg/kg MMB4 DMS resulted in increased blood pressure, slightly increased heart rate, slightly prolonged corrected QT, and moderately increased respiratory rate. There were no toxicological effects of MMB4 DMS on neurobehavioral function in rats administered up to 340 mg/kg MMB4 DMS.

  15. Quantification of the rat left ventricle force and Ca2+ -frequency relationships: similarities to dog and human.

    Science.gov (United States)

    Taylor, David G; Parilak, Leonard D; LeWinter, Martin M; Knot, Harm J

    2004-01-01

    To measure and quantify the force-frequency (FFR) and Ca(2+)-frequency (CaFR) relationships in isolated rat left ventricular (LV) muscle at physiological heart rates and compare the obtained FFR to that measured in larger mammalian muscle from dog and human using the same experimental protocol. Rat papillary muscle was isolated from the LV of adult male Sprague-Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded with the Ca(2+) indicator Fura-2, allowed to recover from isolation trauma and then subjected to direct electrical stimulation while measuring force production and intracellular Ca(2+) transients. We obtained a positive FFR between 1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial muscle strips from dogs and humans with normal LV function. The FFR reflects the cytosolic Ca(2+) transients in amplitude. Isoproterenol yielded an enhancement in force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of FFR amplitude without changing frequency-dependent shape. We describe an experimental protocol that consistently yields positive FFRs in rat, dog and human LV muscle at stimulation rates between 1 and 4 Hz, without significant qualitative differences. We attribute previously observed negative FFR in rat muscle to an increase in SERCA activity early after excision and preparation of the muscle strips.

  16. Metabolism of tritium- and carbon-14-labeled tiamulin in dogs, rats, and pigs.

    Science.gov (United States)

    Dreyfuss, J; Singhvi, S M; Shaw, J M; Egli, P; Ross, J J; Czok, R; Nefzger-Biessels, M; Battig, F; Schuster, I; Schmook, F

    1979-05-01

    The metabolism of tiamulin hydrogen fumarate, labeled with 3H, 14C, or both, was studied in dogs, rats, and weanling pigs. After a dose of radiolabeled tiamulin, all three species excreted more radioactivity in feces (via bile) than in urine. Dogs absorbed 86% of a single oral dose of tiamulin-3H, and the disposition of the compound was similar after a single or multiple dosage regimen. The ratio of antimicrobial activity to total radioactivity in dog plasma was only about 0.25, and was still less in dog urine. After dosing with tiamulin-14C, rats and pigs excreted at least 1% of the dose as 14CO2 in expired air. In dual-labeled studies, pigs excreted less total 14C than 3H and had greater residues of 14C than 3H in edible tissues, blood, and plasma. After the administration of tiamulin-14C to pigs, radioactivity was incorporated into liver glycogen, indicating metabolic cleavage of the side chain of tiamulin. Tiamulin-3H is the isotopically-labeled compound of choice for studying metabolism and tissue residues in animals.

  17. Cellular biophysics during freezing of rat and mouse sperm predicts post-thaw motility.

    Science.gov (United States)

    Hagiwara, Mie; Choi, Jeung Hwan; Devireddy, Ramachandra V; Roberts, Kenneth P; Wolkers, Willem F; Makhlouf, Antoine; Bischof, John C

    2009-10-01

    Though cryopreservation of mouse sperm yields good survival and motility after thawing, cryopreservation of rat sperm remains a challenge. This study was designed to evaluate the biophysics (membrane permeability) of rat in comparison to mouse to better understand the cooling rate response that contributes to cryopreservation success or failure in these two sperm types. In order to extract subzero membrane hydraulic permeability in the presence of ice, a differential scanning calorimeter (DSC) method was used. By analyzing rat and mouse sperm frozen at 5 degrees C/min and 20 degrees C/min, heat release signatures characteristic of each sperm type were obtained and correlated to cellular dehydration. The dehydration response was then fit to a model of cellular water transport (dehydration) by adjusting cell-specific biophysical (membrane hydraulic permeability) parameters L(pg) and E(Lp). A "combined fit" (to 5 degrees C/min and 20 degrees C/min data) for rat sperm in Biggers-Whitten-Whittingham media yielded L(pg) = 0.007 microm min(-1) atm(-1) and E(Lp) = 17.8 kcal/mol, and in egg yolk cryopreservation media yielded L(pg) = 0.005 microm min(-1) atm(-1) and E(Lp) = 14.3 kcal/mol. These parameters, especially the activation energy, were found to be lower than previously published parameters for mouse sperm. In addition, the biophysical responses in mouse and rat sperm were shown to depend on the constituents of the cryopreservation media, in particular egg yolk and glycerol. Using these parameters, optimal cooling rates for cryopreservation were predicted for each sperm based on a criteria of 5%-15% normalized cell water at -30 degrees C during freezing in cryopreservation media. These predicted rates range from 53 degrees C/min to 70 degrees C/min and from 28 degrees C/min to 36 degrees C/min in rat and mouse, respectively. These predictions were validated by comparison to experimentally determined cryopreservation outcomes, in this case based on motility. Maximum

  18. Epithelial cell kinetics in mouse and rat skin irradiated with electrons

    International Nuclear Information System (INIS)

    McMaster-Schuyler, L.

    1984-02-01

    Experiments were performed to examine the kinetic responses of mouse and rat epidermal cells in vivo after single doses of ionizing radiation including responses of hair follicles at times after irradiation. The labeling indices in both species were reduced to 30 to 50% of control values immediately following irradiation at all the doses. In the rat, the labeling indices recovered and overshot control values within the first three days after 300 to 1200 rads. The mouse labeling indices continued to be suppressed for up to 10 days after 300 to 2400 rads. This indicated that rat G 1 phase epidermal cells recovered three times faster than those of the mouse with respect to the ability to maintain or increase control level cell proliferation after irradiation. After 1800 and 2400 rads, doses which produce skin ulceration, both species showed a reduction in their labeling indices for up to 7 days, indicating that a dose-dependent mechanism of recovery may be operable in the rat. 99 refs., 15 figs., 6 tabs

  19. Qualitative and quantitative differences between taste buds of the rat and mouse

    OpenAIRE

    Ma Huazhi; Yang Ruibiao; Thomas Stacey M; Kinnamon John C

    2007-01-01

    Abstract Background Numerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin ...

  20. Cellular Biophysics During Freezing of Rat and Mouse Sperm Predicts Post-thaw Motility1

    Science.gov (United States)

    Hagiwara, Mie; Choi, Jeung Hwan; Devireddy, Ramachandra V.; Roberts, Kenneth P.; Wolkers, Willem F.; Makhlouf, Antoine; Bischof, John C.

    2009-01-01

    Though cryopreservation of mouse sperm yields good survival and motility after thawing, cryopreservation of rat sperm remains a challenge. This study was designed to evaluate the biophysics (membrane permeability) of rat in comparison to mouse to better understand the cooling rate response that contributes to cryopreservation success or failure in these two sperm types. In order to extract subzero membrane hydraulic permeability in the presence of ice, a differential scanning calorimeter (DSC) method was used. By analyzing rat and mouse sperm frozen at 5°C/min and 20°C/min, heat release signatures characteristic of each sperm type were obtained and correlated to cellular dehydration. The dehydration response was then fit to a model of cellular water transport (dehydration) by adjusting cell-specific biophysical (membrane hydraulic permeability) parameters Lpg and ELp. A “combined fit” (to 5°C/min and 20°C/min data) for rat sperm in Biggers-Whitten-Whittingham media yielded Lpg = 0.007 μm min−1 atm−1 and ELp = 17.8 kcal/mol, and in egg yolk cryopreservation media yielded Lpg = 0.005 μm min−1 atm−1 and ELp = 14.3 kcal/mol. These parameters, especially the activation energy, were found to be lower than previously published parameters for mouse sperm. In addition, the biophysical responses in mouse and rat sperm were shown to depend on the constituents of the cryopreservation media, in particular egg yolk and glycerol. Using these parameters, optimal cooling rates for cryopreservation were predicted for each sperm based on a criteria of 5%–15% normalized cell water at −30°C during freezing in cryopreservation media. These predicted rates range from 53°C/min to 70°C/min and from 28°C/min to 36°C/min in rat and mouse, respectively. These predictions were validated by comparison to experimentally determined cryopreservation outcomes, in this case based on motility. Maximum motility was obtained with freezing rates between 50°C/min and 80

  1. Pharmacokinetics and N-acetylation metabolism of S-methyl-l-cysteine and trans-S-1-propenyl-l-cysteine in rats and dogs.

    Science.gov (United States)

    Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

    2016-11-01

    1. Pharmacokinetics and N-acetylation metabolism of S-methyl-L-cysteine (SMC) and trans-S-1-propenyl-L-cysteine (S1PC) were examined in rats and dogs. SMC and S1PC (2-5 mg/kg) were well absorbed in both species with high bioavailability (88-100%). 2. SMC and S1PC were excreted only to a small extent in the urine of rats and dogs. The small renal clearance values (l/h/kg) indicated the extensive renal reabsorption of SMC and S1PC, which potentially contributed to their long elimination half-lives (>5 h) in dogs. 3. S1PC, but not SMC, underwent N-acetylation extensively in vivo, which can be explained by the relative activities of N-acetylation of S1PC/SMC and deacetylation of their N-acetylated forms, N-acetyl-S1PC/N-acetyl-SMC, in the liver and kidney in vitro. The activities for S1PC N-acetylation were similar to or higher than those for N-acetyl-S1PC deacetylation in liver S9 fractions of rat and dog, whereas liver and kidney S9 fractions of rat and dog had little activity for SMC N-acetylation or considerably higher activities for N-acetyl-SMC deacetylation. 4. Our study demonstrated that the pharmacokinetics of SMC and S1PC in rats and dogs was characterized by high bioavailability and extensive renal reabsorption; however, the extent of undergoing the N-acetylation metabolism was extremely different between SMC and S1PC.

  2. Qualitative and quantitative differences between taste buds of the rat and mouse

    Directory of Open Access Journals (Sweden)

    Ma Huazhi

    2007-01-01

    Full Text Available Abstract Background Numerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin (5-HT, PGP 9.5 and synaptobrevin-2 to determine the percentages of taste cells expressing these markers in taste buds in both rodent species. We also determined the numbers of taste cells in the taste buds as well as taste bud volume. Results There are significant differences (p 3 is smaller than a rat taste bud (64,200 μm3. The numerical density of taste cells in mouse circumvallate taste buds (2.1 cells/1000 μm3 is significantly higher than that in the rat (1.2 cells/1000 μm3. Conclusion These results suggest that rats and mice differ significantly in the percentages of taste cells expressing signaling molecules. We speculate that these observed dissimilarities may reflect differences in their gustatory processing.

  3. Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Ploemen, J.H.T.M.; Jespersen, S.; Greef, J. van der; Verhagen, H.; Bladeren, P.J. van

    1996-01-01

    The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme

  4. Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of Pu from the rat

    International Nuclear Information System (INIS)

    Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

    1975-01-01

    After inhaling 1 to 4 HD (human dose equivalents, i.e., 1 g calcium trisodium N,N-bis (2-bis(carboxymethyl)amino) ethyl) glycinate/70 kg body weight) of Ca-DTPA rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrificed later than 3 weeks after the last exposure. Dogs were anesthetised and administered Ca-DTPA aerosols via an intratracheal catheter for 30 min/day for 5 days. The average dose/exposure was 4 HD. One week following the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks postexposure. Epithelial atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months following the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed

  5. Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available Benign prostatic hyperplasia (BPH is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies.

  6. Distribution of latex particles in lung and lymph node tissues of rats and dogs

    International Nuclear Information System (INIS)

    Mueller, H.L; Muggenburg, B.A.; Gillett, N.A.; Guilmette, R.A.

    1988-01-01

    The distribution of fluorescent poly sytrene microspheres in different lung compartments, with differing particle numbers within individual lung and lymph node cells was examined In methacrylate-embedded tissue slices. Rat tissues were analyzed at 1, 7 and 13 days after particle instillation, dog tissues at 7 and 13 days. A much higher fraction of particles was seen in the lung interstitium and in lung-associated lymph nodes in dogs than in rats. Particle concentrations in TBLN cells were generally very low in both species, but were high in free alveolar cells after high particle numbers were instilled, and increased from 1 to 13 days, suggesting that alveolar cells with few particles were cleared faster than those wth high ingested particle numbers. (author)

  7. Comparison of stem-spermatogonial renewal and mitotic activity in the #betta#-irratiated mouse and rat

    International Nuclear Information System (INIS)

    Erickson, B.H.; Hall, G.G.

    1983-01-01

    The Sprague-Dawley rat exceeds the CRF 1 mouse in number of isolated or purported stem cells per unit area of seminiferous tubule by a factor of 2.1, yet the mouse exceeds the rat in number of first-generation spermatogonia (A 1 ) per unit of tubule by a factor of 1.8. This difference could lead to an interspecies difference in irradiation response and help clarify the identity of spermatogonial stem cell. To test this thesis, mice and rats were irradiated with 600 R of 60 Co #betta#-radiation and killed at postirradiation intervals of 1-16 weeks. Both tubular whole mounts and cross sections were evaluated. The species did not differ in percent survival of isolated spermatogonia, but the mouse exceeded the rat in survival and/or production of A 1 or clonal spermatogonia by a factor of 5. By week 16 after irradiation, the mouse restis had regained 67% of its preirradiation weight, in contrast to the rat's 52%. Clonal renewal was in progress by the end of the 2 (mouse) and 3 (rat) weeks and was substantially complete by the 8 week. In both species the isolated population, however, diminished throughout the first 8 weeks and was renewed between 8 and 16 weeks. Clonal renewal was not accompanied by an increase in the number of isolated spermatogonial mitoses, but was accompanied by increases in the mitotis of pairs and clones and the apparent splitting of existing clones to form additional clones. Thus, the mouse's superiority in the rate and completeness of spermatogonial renewal was apparently due to the attributes of the undifferentiated A 1 spermatogonial clone. (orig.)

  8. Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

    International Nuclear Information System (INIS)

    Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

    2010-01-01

    2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

  9. [Toxicity studies of landiolol hydrochloride (ONO-1101) (1). Single intravenous toxicity study in rats and dogs].

    Science.gov (United States)

    Yamaguchi, K; Kasahara, T; Yanagisawa, Y; Nanba, T; Aze, Y; Shinomiya, K; Yonezawa, H; Fujita, T

    1997-12-01

    Single dose toxicity studies of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, were conducted in Sprague-Dawley (SD) rats and beagle dogs. ONO-1101 was administered intravenously at a dose level of 37.5, 75, 150 or 300 mg/kg to rats of both sexes and 25, 50 or 100 mg/kg to male dogs. In the rat study, 5/6 males in the 150 mg/kg group and all animals in the 300 mg/kg group died during or right after administration. Survivors in the 150 mg/kg group showed temporal hypoactivity, bradypnea, dyspnea, tremor, loss of righting reflex and reddish lacrimation up to 5 min after injection. One male in the 150 mg/kg group had a tendency of suppression on body weight gain. No effects on clinical signs and body weight gain were seen in the 75 mg/kg group or lower. Necropsy findings showed only red tear in the majority of the decedents. In the dog study, all animals died within 6 min after administration in the 100 mg/kg group, showed ataxic gait, rolling and tachypnea followed by bradypnea and gasping/apnea. Incontinence of urine, defecation and vocalization were also seen in each one of two animals before death. Temporal hypoactivity was seen 1 min after administration in the 50 mg/kg group. No clinical signs were seen in the 25 mg/kg group. ONO-1101 did not affect bodyweight or food consumption. Necropsy findings of the decedents showed no abnormalities. It is indicated that the minimum lethal doses are 150 mg/kg in rats and 100 mg/kg in dogs.

  10. Immunohistochemical Examination of Novel Rat Monoclonal Antibodies against Mouse and Human Podoplanin

    International Nuclear Information System (INIS)

    Kaji, Chiaki; Tsujimoto, Yuta; Kato Kaneko, Mika; Kato, Yukinari; Sawa, Yoshihiko

    2012-01-01

    This study aims to develop new monoclonal antibodies (mAbs) against mouse and human podoplanin. Rats were immunized with synthetic peptides, corresponding to amino acids 38–51 of mouse podoplanin or human podoplanin which is 100% homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab-1 (IgG 2a ) and anti-human mAb NZ-1.2 (IgG 2a ) were established. In immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)-expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3 transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40-kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ-1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli, pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to the human salivary gland myoepithelial cells. The immunostaining of paraffin-embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These results indicate that the two novel rat mAbs to the mouse and human/monkey podoplanin are useful for Western-blot and immunostaining of somatic tissues on paraffin-embedded sections as well as frozen sections

  11. Comparison of the endogenous ileal and faecal amino acid excretion in the dog (Canis familiaris) and the rat (Rattus rattus) determined under protein-free feeding and peptide alimentation.

    Science.gov (United States)

    Hendriks, W H; Sritharan, K; Hodgkinson, S M

    2002-10-01

    The aim of the study was to determine and compare the endogenous ileal excretions of nitrogen and amino acids under protein-free and peptide alimentation by the dog and rat. Two diets were prepared, one that was devoid of protein and the other containing 23% enzyme hydrolysed casein. Chromic oxide was included in the diets as an indigestible marker. A total of 10 mixed breed dogs were fed hourly either a protein-free or enzymatically hydrolysed casein diet for a total of 10 days. A faecal sample was obtained from each dog on day 9 while digesta was obtained from the terminal 20 cm of the ileum directly after euthanasia on day 10. A total of 12 8-week-old Sprague-Dawley rats received the same diets as the dogs. A faecal sample from each rat was obtained on day 7 while ileal digesta samples were obtained on day 8. The endogenous ileal excretions of most amino acids were greater in the dogs and rats that received the enzymatically hydrolysed casein diet compared with those receiving the protein free diet. Whereas the pattern of endogenous amino acid excretion was similar in the rats and dogs, the dogs excreted a significantly greater amount of nitrogen (1.91 vs. 2.27 and 1.63 vs. 4.12 g/kg dry matter intake for the protein-free and peptide alimentation method, respectively) and all amino acids except for glycine, isoleucine and leucine. Endogenous ileal amino acid excretions are higher in dogs compared to omnivorous animals such as rats and pigs but similar to the carnivorous cat.

  12. Effects of Solutol (Kolliphor) and cremophor in polyethylene glycol 400 vehicle formulations in Sprague-Dawley rats and beagle dogs.

    Science.gov (United States)

    Stokes, Alan H; Kemp, Daniel C; Faiola, Brenda; Jordan, Holly L; Merrill, Christine L; Hailey, James R; Brown, Randy E; Bailey, David W

    2013-01-01

    When conventional vehicles (eg, methylcellulose and water) impart inadequate physical, chemical, and/or biological properties for proper toxicological assessment of test article formulations, nonconventional vehicles may be considered. Often toxicity data for nonconventional vehicle formulations are limited. Studies were conducted to collect toxicity data from a rodent and a non-rodent species given 2 nonconventional vehicles, Solutol HS15/polyethylene glycol (PEG) 400 and Cremophor RH40/PEG 400, with differing formulations and dose volumes (10 mL/kg for rats; 2 or 5 mL/kg for dogs). In rats, both vehicles caused increase in kidney weights (males only) and decrease in thymic weights (males only) without concurrent microscopic findings; altered urine electrolytes, minimally decreased serum electrolytes (males only), and increased serum total cholesterol (females only) were also present. The Cremophor formulation was also associated with increased serum urea (males only) and urine phosphorus: creatinine. For rats given the Solutol formulation, both genders had decreased urine glucose parameters and males had increased urine volume. In dogs, loose/watery feces and emesis were present given either vehicle, and mucus-cell hyperplasia of the ileum was present given the Solutol formulation. Increased red blood cell mass and decreased urine volume in dogs given 30% Solutol/70% PEG 400 (5 mL/kg/d) were likely due to subclinical dehydration and hemoconcentration. For the Cremophor formulations, dose volume-dependent increased incidence of minimal subepithelial gastric hemorrhage was noted in dogs, and dogs given 5 mL/kg/d showed increased serum urea nitrogen. Overall, regardless of the formulation or dose volume, neither vehicle produced overt toxicity in either species, but the Solutol formulation produced fewer effects in rats. Generally, lower dose volumes minimized the severity and/or incidence of findings.

  13. A phylogenomic study of human, dog, and mouse.

    Directory of Open Access Journals (Sweden)

    Gina Cannarozzi

    2007-01-01

    Full Text Available In recent years the phylogenetic relationship of mammalian orders has been addressed in a number of molecular studies. These analyses have frequently yielded inconsistent results with respect to some basal ordinal relationships. For example, the relative placement of primates, rodents, and carnivores has differed in various studies. Here, we attempt to resolve this phylogenetic problem by using data from completely sequenced nuclear genomes to base the analyses on the largest possible amount of data. To minimize the risk of reconstruction artifacts, the trees were reconstructed under different criteria-distance, parsimony, and likelihood. For the distance trees, distance metrics that measure independent phenomena (amino acid replacement, synonymous substitution, and gene reordering were used, as it is highly improbable that all of the trees would be affected the same way by any reconstruction artifact. In contradiction to the currently favored classification, our results based on full-genome analysis of the phylogenetic relationship between human, dog, and mouse yielded overwhelming support for a primate-carnivore clade with the exclusion of rodents.

  14. Characterization of differential cocaine metabolism in mouse and rat through metabolomics-guided metabolite profiling.

    Science.gov (United States)

    Yao, Dan; Shi, Xiaolei; Wang, Lei; Gosnell, Blake A; Chen, Chi

    2013-01-01

    Rodent animal models have been widely used for studying neurologic and toxicological events associated with cocaine abuse. It is known that the mouse is more susceptible to cocaine-induced hepatotoxicity (CIH) than the rat. However, the causes behind this species-dependent sensitivity to cocaine have not been elucidated. In this study, cocaine metabolism in the mouse and rat was characterized through LC-MS-based metabolomic analysis of urine samples and were further compared through calculating the relative abundance of individual cocaine metabolites. The results showed that the levels of benzoylecgonine, a major cocaine metabolite from ester hydrolysis, were comparable in the urine from the mice and rats treated with the same dose of cocaine. However, the levels of the cocaine metabolites from oxidative metabolism, such as N-hydroxybenzoylnorecgonine and hydroxybenzoylecgonine, differed dramatically between the two species, indicating species-dependent cocaine metabolism. Subsequent structural analysis through accurate mass analysis and LC-MS/MS fragmentation revealed that N-oxidation reactions, including N-demethylation and N-hydroxylation, are preferred metabolic routes in the mouse, while extensive aryl hydroxylation reactions occur in the rat. Through stable isotope tracing and in vitro enzyme reactions, a mouse-specific α-glucoside of N-hydroxybenzoylnorecgonine and a group of aryl hydroxy glucuronides high in the rat were identified and structurally elucidated. The differences in the in vivo oxidative metabolism of cocaine between the two rodent species were confirmed by the in vitro microsomal incubations. Chemical inhibition of P450 enzymes further revealed that different P450-mediated oxidative reactions in the ecgonine and benzoic acid moieties of cocaine contribute to the species-dependent biotransformation of cocaine.

  15. In vivo behavior of 111In-DTPA in rat and mouse after intra-ventricular administration

    International Nuclear Information System (INIS)

    Matsushima, Hiroaki; Kato, Makoto; Sugimura, Yukiharu; Hazue, Masaaki

    1977-01-01

    In vivo behavior of 111 In-DTPA in rat and mouse after intra-ventricular administration was studied. Thus, 50μCi and 35μCi of 111 In-DTPA was injected intraventricularly to rat and mouse respectively. At specific time intervals, the animals were sacrificed, then distribution in organs was determined by radioactivity counting and autoradiographic method. Urinary and fecal excretion were separately collected and excretion rates were estimated. Metabolites in urine of rat were examined with chromatography. A part of 111 In-DTPA injected intra-ventricularly to the animals migrated to subarachnoid space, then radioactivity in cerebrospinal fluid effused into blood with about 1 hr initial half-life. Blood clearance was also rapid, about 1 hr after administration the blood level reached maximum and then decreased showing an initial half-life of about 1 hr. The predominant excretion route in rat was urinary and about 90% and 5% of administered dose were excreted within 48 hr through urine and feces respectively. Judging from the Rf-value of radioactivity peak on chromatograms, 111 In-DTPA seems to be excreted without suffering any metabolic change. Concerning to the behavior of 111 In-DTPA in male and female rat, no difference was observed, and the distribution pattern of 111 In-DTPA in mouse was similar to that of rat. (auth.)

  16. Vasopressin levels in plasma and urine of man, dogs and rats, as measured by radioimmunoassay, ch. 1

    International Nuclear Information System (INIS)

    Dogterom, J.; Buijs, R.M.; Wimersma Greidanus, Tj.B. van.

    1977-01-01

    A radioimmunoassay (RIA) of arginine-8-vasopressin (AVP) is reported. The production of antisera and labelled hormone is described. The antibodies are characterized with respect to their binding capacity, specificity and resulting sensitivity in the standard curves. An extraction procedure of AVP from body fluids appeared to be necessary and was performed with activated Vycor glass powder. Other adsorbents were tested as well. The results of the assay indicate that 0.5 pg AVP/ml plasma can be detected. The calculations of the data are fully automized using a Fortran IV programme for a digital computer. With this assay, basal AVP levels were measured in the plasma and urine of man, dogs and rats. In these species, plasma levels were in the range of 0.0-3.0 pg/ml. In addition, plasma AVP levels in rats and dogs were measured after different periods of water deprivation. In rats, AVP increase reached its maximum after 48 hrs of water deprivation: 27.1 +- 3.4 pg/ml

  17. Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

    International Nuclear Information System (INIS)

    Hustvedt, S.O.

    1997-01-01

    Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14 C-MnDPDP or 54 MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moeity is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moeity is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. (orig./AJ)

  18. Comparative studies on the ossification in several experimental animals

    International Nuclear Information System (INIS)

    Matsuoka, Osamu; Fukuda, Shun

    1978-01-01

    For estimating the risk of the bone seeking radionuclides in man, it is necessary to extrapolate the data of experimental animals to those of man. Detailed information on the biological stages of development, especially on bone growth of several experimental animals and of man is required for better extrapolation. Multi-species comparison of bone growth and ossification was carried out in several mammalian species such as mouse, rat, dog and monkey. The appearance, ossifying process and fusion of the secondary ossification centers in extremities were selected as indicators of the biological stage of bone. The observation of the secondary ossification centers was made by radiography. The maturity process of the secondary ossification centers in each animal was illustrated. The ossifying process of the secondary ossification center could be divided into the following three categories; (1) the acute ossification observed in mouse, rat, dog and monkey (2) the delayed ossification observed in mouse, rat, dog and monkey, (3) the incomplete ossification without complete fusion which is specific in mouse and rat, appeared and continued up to at least 27 weeks in mouse and up to 134 weeks in rat. The results of the study suggested that a mouse 17 weeks old, a rat 17 - 21 weeks old, a dog (beagle) 14 months old and a monkey about 6 years old may correspond to a man about 20 years old. (author)

  19. Subacute intramuscular toxicity of the acetylcholinesterase reactivating agent Hi-6 in rats and dogs. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Levine, B.S.; Tomlinson, M.J.

    1993-12-31

    Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture,and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.

  20. Myocardial kinetics of hexakis (trimethylphosphite) technetium-99m (I) chloride (Tc-TMP) in rats, rabbits, dogs, cats and pigs

    International Nuclear Information System (INIS)

    Robbins, M.S.; Adams, M.D.

    1984-01-01

    Tc-TMP is readily taken up by the myocardium following intravenous administration to rats and dogs. In order to assess its potential as a myocardial perfusion imaging agent, the biodistribution and pharmacokinetics of Tc-TMP were evaluated following intravenous administration to rats, rabbits, dogs, cats and miniature pigs. Rats and rabbits were killed at several time points within a 24 hr period after treatment and tissue samples were assayed for radioactivity. In rats, estimated heart, liver and lung half-lives were 14.4 hr, 24 min and 40 min, respectively. In rabbits, 0.6% dose/g was observed in the heart at 30 min. Corresponding heart/blood, heart/liver and heart/lung ratios were 39.1, 10.7 and 5.1. Gamma camera imaging experiments were conducted in rabbits, dogs, cats and pigs over a 1-2 hr period following administration of Tc-TMP. All species exhibited myocardial uptake resulting in sustained visualization, although myocardial image intensity was less pronounced in the pig compared to the other species. Regions of interest were selected over the heart, liver and background, and time-activity curves were generated. Minimal myocardial clearance was observed in all species during the imaging time course. Hepatic activity was rapidly cleared in rabbits and pigs (t1/2 < 1.0 hr) resulting in improved heart/liver ratios at later time intervals. The myocardial accumulation and retention of Tc-TMP, demonstrated in five species, supports clinical evaluation as a myocardial imaging agent

  1. Distribution of /sup 14/C-labelled acrylamide and betaine in foetuses of rats, rabbits, beagle dogs and miniature pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, G.J.; Miller, E.; Sapienza, P.P.; Michel, T.C.; King, M.T.; Turner, V.A.; Blumenthal, H.; Jackson, W.E.; Levin, S.

    1983-02-01

    (/sup 14/C)Acrylamide and (/sup 14/C)betaine hydrochloride were administered in a single iv dose to pregnant rats, rabbits, beagle dogs and miniature pigs late in gestation (1-2 days before expected parturition). Dosages used were 10 mg/kg for rats and 5 mg/kg for the other species. The compounds were allowed to equilibrate in the animal (for 1 hr in rats and for 2 hr in the other species); the dam was then killed and the foetuses were removed by caesarean section. Each foetus was weighed and analysed for radioactivity, either by homogenization of the whole foetus (rat and rabbit) or by determining separately the radioactivity in individual organs and tissues (dog and pig). Foetal uptake of the polar compound betaine hydrochloride was much lower than that of the more lipophilic acrylamide. The sex of the foetus did not appear to affect uptake of either compound. There were no significant differences in total uptake of isotope attributable to the position of the foetus within the uterus in any of the four species given either acrylamide or betaine. Similarly, uterine position did not affect the uptake of acrylamide or betaine by individual tissues of foetal dogs or pigs. Since the distributions of /sup 14/C-labelled acrylamide and betaine hydrochloride were essentially uniform throughout a litter, it would not be necessary to sample all of the members of a litter to obtain a representative picture of foetal distribution.

  2. Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

    Directory of Open Access Journals (Sweden)

    Robert C. Karn

    2013-12-01

    Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

  3. Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration.

    Science.gov (United States)

    Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Hawk, Michael A; Croutch, Claire R; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average T max values ranging from 5 to 30 minutes. Although C max values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, C max and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.

  4. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  5. Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation.

    Science.gov (United States)

    Du, Yang; Deng, Wenjun; Wang, Zixing; Ning, MingMing; Zhang, Wei; Zhou, Yiming; Lo, Eng H; Xing, Changhong

    2017-04-01

    Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

  6. Reversed-phase high-performance liquid chromatographic analyses of insulin biosynthesis in isolated rat and mouse islets

    DEFF Research Database (Denmark)

    Linde, S; Hansen, Bruno A.; Welinder, B S

    1989-01-01

    deletion compared to rat C-peptide I. A marked species difference in the ratio between insulin I and II was observed, i.e., 2:1 in the rat and 1:2 in the mouse. Pulse-chase experiments in rat islets have demonstrated that the ratio between insulin I and II in newly synthesized insulin is higher than...

  7. Use of Terbinafine in Mouse and Rat Models of Pneumocystis carinii Pneumonia

    Science.gov (United States)

    Walzer, Peter D.; Ashbaugh, Alan

    2002-01-01

    Terbinafine, an allylamine used to treat onychomycosis, has been reported to be active against rat Pneumocystis carinii in vitro and in vivo. By contrast, our in vitro data showed that the 50% inhibitory concentration of terbinafine against rat P. carinii is 3.7 μg/ml, a level that cannot be clinically achieved in serum. In the present study, terbinafine administered orally at doses of 20 to 400 mg/kg/day and 50 to 250 mg/kg/day was ineffective therapy for mouse and rat models of pneumocystosis, respectively. These results emphasize the complexities of P. carinii drug testing and the need for caution before considering studies in humans. PMID:11796365

  8. The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.

    Science.gov (United States)

    Ahearn, K; Akkouris, G; Berry, P R; Chrissluis, R R; Crooks, I M; Dull, A K; Grable, S; Jeruzal, J; Lanza, J; Lavoie, C; Maloney, R A; Pitruzzello, M; Sharma, R; Stoklasek, T A; Tweeddale, J; King, T R

    2002-01-01

    Recent evidence has indicated that the recessive mutation affecting hypotrichosis in the Charles River (CR) "hairless" rat does not involve the hairless gene (hr) on rat chromosome 15. To determine if this mutation might be allelic (or orthologous) with any other previously mapped hypotrichosis-generating mutation in mammals, we have produced a panel of backcross rats segregating for the CR hairless rat mutation as well as numerous other markers from throughout the rat genome. Analysis of this panel has located the CR hairless rat's hypotrichosis-generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in rat (fz) and the frizzy mutation in mouse (fr) have been previously localized. Intercrossing fz/fz and CR hairless rats produced hybrid offspring with abnormal hair, showing that these two rat mutations are allelic. We suggest that the CR hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the mouse fr mutation.

  9. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  10. Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

    Science.gov (United States)

    Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

    2016-07-01

    Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

  11. Characterization of xenogeneic mouse-to-rat bone marrow chimeras. I. Examination of hematologic and immunologic function

    International Nuclear Information System (INIS)

    Wade, A.C.; Luckert, P.H.; Tazume, S.; Niedbalski, J.L.; Pollard, M.

    1987-01-01

    Eighteen xenogeneic chimeric rats (survival: greater than 100 days) were established by transplanting bone marrow cells from femurs of 10 gnotobiotic CFW mice into each germfree Sprague-Dawley or Wistar rat. The erythrocytes circulating in the rats were of mouse origin as determined by hemagglutination. Hemoglobin electrophoresis, radial immunodiffusion for IgG, and assay of granulocytic neutrophils for leukocyte alkaline phosphatase verified that true chimerism was achieved. The extent of hematological and immunological reconstitution varied. In general, hematocrit levels were low to normal, white blood cell counts and differentials were within normal limits, and serum protein levels were normal. Levels of circulating IgG of each species were comparable to those of germfree rat and mouse controls. Natural killer (NK) activity was depressed, a phenomenon that may be attributable to the radiation treatment of recipients, or to failure to transfer NK cells or precursors. Mitogenic stimulation reactions were varied, but most chimeric rats demonstrated moderately depressed responses. Reactions as a whole suggested that gnotobiotic rats with xenogeneic bone marrow are incompletely reconstituted, both hematologically and immunologically. No acute graft-versus-host reaction was seen

  12. Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

    Science.gov (United States)

    Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

    2014-08-01

    CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells

    Energy Technology Data Exchange (ETDEWEB)

    Kovalova, Natalia, E-mail: kovalova@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Nault, Rance, E-mail: naultran@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Crawford, Robert, E-mail: crawfo28@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States)

    2017-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12 h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation. Therefore, we hypothesized that TCDD treatment across three different species (mouse, rat and human) triggers a conserved, B cell-specific mechanism that is involved in TCDD-induced immunosuppression. RNA sequencing (RNA-Seq) was used to identify B cell-specific orthologous genes that are differentially expressed in response to TCDD in primary mouse, rat and human B cells. Time course studies identified TCDD-elicited differential expression of 515 human, 2371 mouse and 712 rat orthologous genes over the 24-h period. 28 orthologs were differentially expressed in response to TCDD in all three species. Overrepresented pathways enriched in all three species included cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton and pathways in cancer. Differentially expressed genes functionally associated with cell-cell signaling in humans, immune response in mice, and oxidation reduction in rats. Overall, these results suggest that despite the conservation of the AhR and its signaling mechanism, TCDD elicits species-specific gene expression changes. - Highlights: • Kovalova TAAP Highlights Nov. 2016 • RNA-Seq identified TCDD-induced gene expression in PWM-activated primary B cells. • TCDD elicited differential expression of 515 human, 2371 mouse and 712

  14. Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Xiaofang Zhang

    2016-11-01

    Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

  15. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin ( AG ) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro . In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability ( t 1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  16. Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

    Science.gov (United States)

    Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

    2014-01-01

    Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if

  17. In vivo metabolism of cannabinol by the mouse and rat and a comparison with a metabolism of delta 1-tetrahydrocannabinol and cannabidiol.

    Science.gov (United States)

    Harvey, D J; Martin, B R; Paton, W D

    1977-12-01

    The in vivo liver metabolism of cannabinol has been studied in the mouse and rat by combined gas chromatography and mass spectrometry. Cannabinol glucuronide was the major metabolite of cannabinol in the mouse and was accompanied by relatively large amounts of 7-hydroxycannabinol, cannabinol-7-oic acid and their corresponding glucuronide conjugates. Lower concentrations of glucuronides were found in the rat. Two series of disubstituted metabolites were found containing either a 7-hydroxyl or a 7-carboxylic acid group and a second hydroxyl group in the 1 inch-4 inch positions of the sidechain. These were of low concentration in the mouse but higher in the rat; 1 inch-hydroxy metabolites were particularly abundant in the latter species. Also found in the rat livers were small amounts of sidechain monohydroxy metabolites and larger quantities of 4 inches, 5 inches-bisnorcannabinol-3 inches-oic acid; these were absent in the mouse. The metabolites were identified using the trimethylsilyl (TMS), [2H9] TMS and methyl ester-TMS derivatives, and by reduction of acid metabolites with lithium aluminium deuteride to the corresponding alcohols.

  18. METABOLISM AND DNA ADDUCT FORMATION OF 2-ACETYLAMINOFLUORENE BY BLADDER EXPLANTS FROM HUMAN, DOG, MONKEY, HAMSTER AND RAT

    Science.gov (United States)

    It is concluded that bladder explants of the human, dog, monkey, hamster, and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the fo...

  19. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

    NARCIS (Netherlands)

    S.L. Macrae (Sheila L.); Q. Zhang (Quanwei); C. Lemetre (Christophe); I. Seim (Inge); R.B. Calder (Robert B.); J.H.J. Hoeijmakers (Jan); Y. Suh (Yousin); V.N. Gladyshev (Vadim N.); A. Seluanov (Andrei); V. Gorbunova (Vera); J. Vijg (Jan); Z.D. Zhang (Zhengdong D.)

    2015-01-01

    textabstractGenome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM

  20. Comparison of the vanadate oxidase method with the diazo method for serum bilirubin determination in dog, monkey, and rat.

    Science.gov (United States)

    Ameri, Mehrdad; Schnaars, Henry; Sibley, John; Honor, David

    2011-01-01

    The most widely used method for bilirubin concentration determination is the diazo method, which measures the color of azobilirubin. The vanadate oxidase method is based on oxidation of bilirubin to biliverdin by vanadate. The objective of this study was to compare total and direct bilirubin concentration ([Bt] and [Bd], respectively) determined by the diazo and vanadate oxidase methods in pooled serum samples from dogs, monkeys, and rats spiked with panels of different concentrations of bilirubin standards. Pooled serum samples from 40 dogs, 40 monkeys, and 60 rats were spiked with either ditaurine conjugates of bilirubin or a standard reference material. The results obtained from both assays were compared using Deming regression analysis. The intra- and interassay precision, expressed as a percentage of the coefficient of variation (%CV), was determined for [Bt] and [Bd], and the mean percentage of recovery was calculated. The vanadate oxidase method displayed an excellent correlation (r  =  0.99-1.00) with the diazo method. Using Deming regression, there were minimal negative or positive constant and proportional biases for [Bt] and [Bd]. The precision studies revealed that the vanadate oxidase method has comparable between-run and within-run CVs to those of the diazo method. The recovery study demonstrated that the diazo method more closely approximates the expected values of [Bt]. In conclusion, the vanadate oxidase method is a simple and rapid method that can be employed as an alternative to the diazo method when interfering substances are present in the serum samples of dog, monkey, and rat.

  1. An interspecies comparison of the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey alveolar macrophages in vitro

    International Nuclear Information System (INIS)

    Taya, A.; Carmack, D.B.; Muggenburg, B.A.; Mewhinney, J.A.

    1992-01-01

    Experiments were conducted to study the phagocytosis and dissolution of 241 AmO 2 particles by rat, dog and monkey alveolar macrophages (PAM) in vitro. The phagocytosis and dissolution of 241 AmO 2 particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up 241 AmO 2 particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20h. The PAM of the three species dissolved 241 AmO 2 particles at similar rates; 8-10% was dissolved by 72h. The results of the 241 AmO 2 uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of 241 AmO 2 particles by alveolar macrophages of the three species might be species-independent. (author)

  2. Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.

    Directory of Open Access Journals (Sweden)

    Liao Wang

    Full Text Available Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA sintered at 1200°C and two biphasic calcium phosphate (BCP ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate, sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model.

  3. Increasing the persistence of a heterogeneous behavior chain: Studies of extinction in a rat model of search behavior of working dogs.

    Science.gov (United States)

    Thrailkill, Eric A; Kacelnik, Alex; Porritt, Fay; Bouton, Mark E

    2016-08-01

    Dogs trained to search for contraband perform a chain of behavior in which they first search for a target and then make a separate response that indicates to the trainer that they have found one. The dogs often conduct multiple searches without encountering a target and receiving the reinforcer (i.e., no contraband is present). Understanding extinction (i.e., the decline in work rate when reinforcers are no longer encountered) may assist in training dogs to work in conditions where targets are rare. We therefore trained rats on a search-target behavior chain modeled on the search behavior of working dogs. A discriminative stimulus signaled that a search response (e.g., chain pull) led to a second stimulus that set the occasion for a target response (e.g., lever press) that was reinforced by a food pellet. In Experiment 1 training with longer search durations and intermittent (partial) reinforcement of searching (i.e. some trials had no target present) both led to more persistent search responding in extinction. The loss of search behavior in extinction was primarily dependent on the number of non-reinforced searches rather than time searching without reinforcement. In Experiments 2 and 3, delivery of non-contingent reinforcers during extinction increased search persistence provided they had also been presented during training. Thus, results with rats suggest that the persistence of working dog performance (or chained behavior generally) may be improved by training with partial reinforcement of searching and non-contingent reinforcement during both training and work (extinction). Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  5. Insights from Human/Mouse genome comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  6. Sniffer dogs unleashed.

    Science.gov (United States)

    2018-04-07

    A 10-year conservation project to restore the native bird populations of South Georgia has involved eradicating invasive rodent species. As Daniel Gillett explains, specially trained sniffer dogs are an important part of 'team rat'. British Veterinary Association.

  7. Effect of Rat Medicated Serum Containing You Gui Wan on Mouse Oocyte In Vitro Maturation and Subsequent Fertilization Competence

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Jiang

    2014-01-01

    Full Text Available You Gui Wan (YGW is a classic herbal formula in traditional Chinese medicine (TCM used for the clinical treatment of infertility. This study was to explore whether YGW has an impact on mouse oocyte maturation in vitro and subsequent fertilization competence. Rat medicated serum containing YGW was prepared by orally administrating YGW. Mouse immature oocytes were cultured with YGW medicated serum and compared to those cultured with or without normal rat serum or follicle-stimulating hormone (FSH. YGW medicated serum significantly increased the percentages of matured oocytes when compared to the groups with or without normal rat serum (P < 0.01. Furthermore, YGW medicated serum increased the rate of in vitro fertilization (IVF when compared to the groups treated with FSH and with or without normal rat serum (P < 0.001. YGW medicated serum also had significant effects on the mRNA expressions of PKA, CREB, MAPK, PKC, PKG, and MPF and the concentrations of cAMP, cGMP, and NO in matured oocytes. These results indicate that YGW can promote mouse oocyte maturation and IVF in vitro. Signaling pathways, such as the cAMP/PKA/MAPK, the PKC-MAPK, and the NO-cGMP-PKG pathway, which are similar to those induced by FSH, may be responsible for this action.

  8. Comparative histology of mouse, rat, and human pelvic ligaments.

    Science.gov (United States)

    Iwanaga, Ritsuko; Orlicky, David J; Arnett, Jameson; Guess, Marsha K; Hurt, K Joseph; Connell, Kathleen A

    2016-11-01

    The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

  9. Inhaled 239PuO2 and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.

    1988-08-01

    Rats and beagle dogs were given doses of 60 Co gamma radiation and/or body burdens of 239 PuO 2 within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs

  10. Radiation damages to cell membranes of dogs and rats quantitatively estimated by changes in sedimentation behaviour of erythrocytes

    International Nuclear Information System (INIS)

    Mikhajlov, V.F.; Potemkin, L.A.

    1985-01-01

    It was shown that injury to plasma membranes leads to a change in the sedimentation behaviour of erythrocytes: the maximum effect is produced when a protein component of the membrane is affected. The same dose dependent character of the change in erythrocyte sedimentation in urografine are observed during the first 24 h after γ-irradiation of rats and dogs

  11. Possible mechanism for species difference on the toxicity of pivalic acid between dogs and rats

    International Nuclear Information System (INIS)

    Yamaguchi, Toshiro; Nakajima, Yoshitsugu; Nakamura, Yutaka

    2006-01-01

    In a high dose toxicity study of pivalic acid (PA), PA caused skeletal muscle disorder in dog, and a significant increase of pivaloyl carnitine (PC) was observed in canine muscle, but not in rat muscle. In order to understand species difference of the toxicity of PA, we compared the in vitro metabolism of PA among dog, rat and rabbit, especially focussing on the carnitine conjugate. Canine muscle showed low, but significant carnitine conjugating activity, while that of rat was negligible. Canine kidney mitochondria had significant activity in the pivaloyl CoA synthesis (7 nmol/mg protein/h), but muscle mitochondria showed only trace activity. Both kidney and muscle mitochondria displayed similar carnitine acyltransferase activity (2-3 nmol/mg protein/h) towards pivaloyl CoA. On the other hand, with respect to the activity of carnitine acyltransferase in the reverse direction using PC as substrate, canine muscle mitochondria showed higher activity than that of kidney mitochondria. This means that PC is not the final stable metabolite, but is converted easily to pivaloyl CoA in canine muscle. These results suggest one of the possible mechanisms for canine selective muscle disorder to be as follows. Only canine muscle can metabolize PA to its carnitine conjugate slowly, but significantly. In canine muscle, PC is not the final stable metabolite; it is easily converted to pivaloyl CoA. As carnitine conjugation is thought to be the only detoxification metabolic route in canine muscle, under certain circumstances such as carnitine deficiency, the risk of exposure with toxic pivaloyl CoA might increase and the CoASH pool in canine muscle might be exhausted, resulting in toxicity in canine muscle

  12. Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

    Science.gov (United States)

    Schuhmacher, Laura-Nadine; Smith, Ewan St John

    2016-12-13

    Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

  13. Structural and functional development of rat and mouse gastric mucous cells in relation to their proliferative activity

    International Nuclear Information System (INIS)

    Wattel, W.

    1978-01-01

    An investigation has been carried out to find a relation between the differentiation and the mitotic activity of gastric mucous cells of the rat and the mouse. It is shown that the bulk mucous production is carried out by the older, non-proliferative, surface mucous cells that line the foveolae and the gastric surface. One experiment describes the renewal of mouse gastric mucous cells following fast neutron irradiation. (C.F.)

  14. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations

    Science.gov (United States)

    Abstract: The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluorid...

  15. The effect of centrifugation at various g force levels on rheological properties of rat, dog, pig and human red blood cells.

    Science.gov (United States)

    Kiss, Ferenc; Toth, Eniko; Miszti-Blasius, Kornel; Nemeth, Norbert

    2016-01-01

    Laboratory investigations often require centrifugation of blood samples for various erythrocyte tests. Although there is a lack of data about the effect of centrifugation at various g force levels on erythrocyte rheological properties. We aimed to investigate the effect of a 10-minute centrifugation at 500, 1000 or 1500 g at 15°C of rat, dog, pig and human venous (K3-EDTA, 1.5 mg/ml) blood samples. Hematological parameters, erythrocyte deformability, cell membrane stability, osmotic gradient ektacytometry (osmoscan) and erythrocyte aggregation were determined. Hematological and erythrocyte deformability parameters showed interspecies differences, centrifugation caused no significant alterations. Cell membrane stability for human erythrocytes centrifuged at higher g level showed less decrease in deformability. Osmoscan O min parameter showed slight elevation in dog centrifuged aliquots. Erythrocyte aggregation parameters changed unexpectedly. Rat and dog erythrocyte aggregation indices significantly dropped in centrifuged aliquots. Pig erythrocyte aggregation indices increased significantly after centrifugation. Human erythrocyte aggregation was the most stable one among the investigated species. The used centrifugation protocols caused the largest alterations in erythrocyte aggregation in a controversial way among the investigated species. On the other hand, erythrocyte deformability parameters were stable, cell membrane stability and osmoscan data show minor shifts.

  16. Isolation of three novel rat and mouse papillomaviruses and their genomic characterization.

    Directory of Open Access Journals (Sweden)

    Eric Schulz

    Full Text Available Despite a growing knowledge about the biological diversity of papillomaviruses (PV, only little is known about non-human PV in general and about PV mice models in particular. We cloned and sequenced the complete genomes of two novel PV types from the Norway rat (Rattus norvegicus; RnPV2 and the wood mouse (Apodemus sylvaticus; AsPV1 as well as a novel variant of the recently described MmuPV1 (originally designated as MusPV from a house mouse (Mus musculus; MmuPV1 variant. In addition, we conducted phylogenetic analyses using a systematically representative set of 79 PV types, including the novel sequences. As inferred from concatenated amino acid sequences of six proteins, MmuPV1 variant and AsPV1 nested within the Beta+Xi-PV super taxon as members of the Pi-PV. RnPV2 is a member of the Iota-PV that has a distant phylogenetic position from Pi-PV. The phylogenetic results support a complex scenario of PV diversification driven by different evolutionary forces including co-divergence with hosts and adaptive radiations to new environments. PV types particularly isolated from mice and rats are the basis for new animal models, which are valuable to study PV induced tumors and new treatment options.

  17. Comparison between the Counter Immunoelectrophoresis Test and Mouse Neutralization Test for the Detection of Antibodies against Rabies Virus in Dog Sera

    Directory of Open Access Journals (Sweden)

    Luzia Helena Queiroz da Silva

    2002-03-01

    Full Text Available The detection of rabies antibodies is extremely valuable for epidemiological studies, determination of immune status in man, animals, and for the diagnosis of the disease. Several serological procedures have been described for this purpose. The present study reports a comparison between counterimmunoelectrophoresis test (CIET and mouse neutralization test (MNT in the detection of antibodies against rabies virus from 212 serum samples of vaccinated dogs. The agreement between both techniques was 79.7% and a significative association was demonstrated. The correlation coefficients between MNT and the CIET titers was determined considering 88 samples showing positive results in both techniques [CIET = 2 and MNT = 5 (0.13 IU/ml] and resulted r² = 0.7926 (p < 0.001. The performance of CIET system was technically simple, cheap and rapid, and thereby it could be useful for serological monitoring of dog vaccination campaigns as well as for individual analysis.

  18. Recent mouse and rat methods for the study of experimental oral candidiasis.

    Science.gov (United States)

    Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

    2013-07-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

  19. Recent mouse and rat methods for the study of experimental oral candidiasis

    Science.gov (United States)

    Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

    2013-01-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

  20. Differences in social interaction- vs. cocaine reward in mouse vs. rat.

    Science.gov (United States)

    Kummer, Kai K; Hofhansel, Lena; Barwitz, Constanze M; Schardl, Aurelia; Prast, Janine M; Salti, Ahmad; El Rawas, Rana; Zernig, Gerald

    2014-01-01

    We previously developed rat experimental models based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley (SD) rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2) prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction). In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion (CPA) to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs. 79% for rats. In animals that were concurrently conditioned for social interaction vs. cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats. Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs. social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats.

  1. Differences in social interaction- vs cocaine reward in rat vs mouse

    Directory of Open Access Journals (Sweden)

    Kai K Kummer

    2014-10-01

    Full Text Available We previously developed rat experimental models based on the conditioned place preference (CPP paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley rat (1 reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2 prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction. In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs 79% for rats. In animals that were concurrently conditioned for social interaction vs cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats.Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats.

  2. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

    Science.gov (United States)

    MacRae, Sheila L; Zhang, Quanwei; Lemetre, Christophe; Seim, Inge; Calder, Robert B; Hoeijmakers, Jan; Suh, Yousin; Gladyshev, Vadim N; Seluanov, Andrei; Gorbunova, Vera; Vijg, Jan; Zhang, Zhengdong D

    2015-04-01

    Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. The truth about mouse, human, worms and yeast

    Directory of Open Access Journals (Sweden)

    Nelson David R

    2004-01-01

    Full Text Available Abstract Genome comparisons are behind the powerful new annotation methods being developed to find all human genes, as well as genes from other genomes. Genomes are now frequently being studied in pairs to provide cross-comparison datasets. This 'Noah's Ark' approach often reveals unsuspected genes and may support the deletion of false-positive predictions. Joining mouse and human as the cross-comparison dataset for the first two mammals are: two Drosophila species, D. melanogaster and D. pseudoobscura; two sea squirts, Ciona intestinalis and Ciona savignyi; four yeast (Saccharomyces species; two nematodes, Caenorhabditis elegans and Caenorhabditis briggsae; and two pufferfish (Takefugu rubripes and Tetraodon nigroviridis. Even genomes like yeast and C. elegans, which have been known for more than five years, are now being significantly improved. Methods developed for yeast or nematodes will now be applied to mouse and human, and soon to additional mammals such as rat and dog, to identify all the mammalian protein-coding genes. Current large disparities between human Unigene predictions (127,835 genes and gene-scanning methods (45,000 genes still need to be resolved. This will be the challenge during the next few years.

  4. A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis

    Science.gov (United States)

    2008-09-01

    idoxifene has not been developed further because of concerns about uterine prolapse (299]. This side effect is not seen with tamoxifen 5.6.4 Droloxifene...various species (rat, mouse, mon- key, and dog ). Themajor route of excretion of radioactivitywas in the feces. The rat and dog were used to show that...identified in the dog [40]. This phenolic metabolite without the dimethylaminoethyl side chain is a full estrogen [47,49]. The dimethylaminoethoxy side

  5. In vitro hepatic microsomal metabolism of meloxicam in koalas (Phascolarctos cinereus), brushtail possums (Trichosurus vulpecula), ringtail possums (Pseudocheirus peregrinus), rats (Rattus norvegicus) and dogs (Canis lupus familiaris).

    Science.gov (United States)

    Kimble, B; Li, K M; Valtchev, P; Higgins, D P; Krockenberger, M B; Govendir, M

    2014-04-01

    Quantitative and qualitative aspects of in vitro metabolism of the non-steroidal anti-inflammatory drug meloxicam, mediated via hepatic microsomes of specialized foliage (Eucalyptus) eating marsupials (koalas and ringtail possums), a generalized foliage eating marsupial (brushtail possum), rats, and dogs, are described. Using a substrate depletion method, intrinsic hepatic clearance (in vitro Clint) was determined. Significantly, rates of oxidative transformation of meloxicam, likely mediated via cytochromes P450 (CYP), were higher in marsupials compared to rats or dogs. The rank order of apparent in vitro Clint was brushtail possums (n=3) (mean: 394μL/min/mg protein), >koalas (n=6) (50), >ringtail possums (n=2) (36) (with no significant difference between koalas and ringtail possums), >pooled rats (3.2)>pooled dogs (in which the rate of depletion, as calculated by the ratio of the substrate remaining was <20% and too slow to determine). During the depletion of meloxicam, at a first-order rate constant, 5-hydroxymethyl metabolite (M1) was identified in the brushtail possums and the rat as the major metabolite. However, multiple hydroxyl metabolites were observed in the koala (M1, M2, and M3) and the ringtail possum (M1 and M3) indicating that these specialized foliage-eating marsupials have diverse oxidation capacity to metabolize meloxicam. Using a well-stirred model, the apparent in vitro Clint of meloxicam for koalas and the rat was further scaled to compare with published in vivo Cl. The closest in vivo Cl prediction from in vitro data of koalas was demonstrated with scaled hepatic Cl(total) (average fold error=1.9) excluding unbound fractions in the blood and microsome values; whereas for rats, the in-vitro scaled hepatic Cl fu(blood, mic), corrected with unbound fractions in the blood and microsome values, provided the best prediction (fold error=1.86). This study indicates that eutherians such as rats or dogs serve as inadequate models for dosage

  6. Revisiting the missing protein-coding gene catalog of the domestic dog

    Directory of Open Access Journals (Sweden)

    Galibert Francis

    2009-02-01

    Full Text Available Abstract Background Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000, compared to the over 20,000 reported for other mammalian species. Of particular interest are the more than 400 of genes annotated in primates and rodent genomes, but missing in dog. Results Using over 14,000 orthologous genes between human, chimpanzee, mouse rat and dog, we built multiple pairwise synteny maps to infer short orthologous intervals that were targeted for characterizing the canine missing genes. Based on gene prediction and a functionality test using the ratio of replacement to silent nucleotide substitution rates (dN/dS, we provide compelling structural and functional evidence for the identification of 232 new protein-coding genes in the canine genome and 69 gene losses, characterized as undetected gene or pseudogenes. Gene loss phyletic pattern analysis using ten species from chicken to human allowed us to characterize 28 canine-specific gene losses that have functional orthologs continuously from chicken or marsupials through human, and 10 genes that arose specifically in the evolutionary lineage leading to rodent and primates. Conclusion This study demonstrates the central role of comparative genomics for refining gene catalogs and exploring the evolutionary history of gene repertoires, particularly as applied for the characterization of species-specific gene gains and losses.

  7. Effect of low dose x irradiation on the succinate dehydrogenase activity of guinea pig, rat and mouse tissues

    Energy Technology Data Exchange (ETDEWEB)

    Shah, V C; Bhatavdekar, J M; Aravinda Babu, K [Gujarat Univ., Ahmedabad (India). Dept. of Zoology

    1976-07-01

    The histochemical changes in succinate dehydrogenase (SDH) were investigated in pectoralis major muscle of guinea pig, rat and mouse after level X-irradiation (72 R and 240 R) and compared with control animals. Biochemical studies were carried out on liver, kidney, muscle (pectoralis major), adrenal and spleen of these animals after low dose local X-irradiation and compared with control animals. Changes in SDH activity were studied up to 72-h post-irradiation, which shows that low dose local X-irradiation leads to increased enzymic activity. The increase in enzymic activity was remarkable in mouse tissues as compared with guinea pig and rat. Adrenals of all the three animals showed significant activation after all the doses of radiation studied. The significance of these results, with special reference to oxidative metabolism, has been discussed.

  8. An ELISA to Detect Serum Antibodies to the Salivary Gland Toxin of Ixodes holocyclus Neumann in Dogs and Rodents

    Directory of Open Access Journals (Sweden)

    S. Hall-Mendelin

    2011-01-01

    Full Text Available The Ixodes holocyclus tick causes paralysis in up to 10,000 companion and domestic animals each year in Australia. Treatment requires the removal of the parasite and the administration of a commercial tick antiserum that is prepared from hyperimmune dogs. Each batch of this serum is initially tested for toxin-neutralising potency in a mouse bioassay that is expensive, time consuming, and subjective. With the aim of developing a rapid in vitro assay to replace the bioassay, we used a partially purified antigen prepared from I. holocyclus salivary glands to develop an ELISA to detect toxin-reactive antibodies in hyperimmune dog sera. The optimised ELISA reliably detected antibodies reactive to I. holocyclus salivary gland antigens. Parallel testing of sera with a negative control antigen prepared from the salivary glands of the nontoxic tick Rhipicephalus (Boophilus microplus provided further evidence that we were detecting toxin-specific antibodies in the assay. Using the ELISA, we could also detect antibodies induced in rats after experimental infestation with I. holocyclus. This assay shows promise as an alternative means of assessing the potency of batches of hyperimmune dog serum and to screen for toxin-reactive monoclonal antibodies produced from immunised rodents.

  9. Radioimmunoassay for serotin - methodology, basal and stimulated hormone concentration in plasma of rats, dogs, rabbits and humans

    International Nuclear Information System (INIS)

    Wittmann, J.K.

    1983-01-01

    A radioimmunoassay for measurement of secretin in the plasma of experimental animals and man has been developed by means of the so-called stripping procedure (pre-treatment of plasma with Quso). The detection limit is about 7 pg/ml at a final dilution of 1:630 000 and an equilibrium constant of 2.1x10 -11 L/M. By means of this system plasma secretin in the species examined can be measured reliably. The coefficients of variation are (percent): The within assay precision (intra-assay) 12, the between assay precision (inter-assay) 23. The median of basal venous plasma secretin are (pg/ml) dog 16, rabbit 0, rat (aorta) 0, rat (porta) 31, man 0. From these studies it is concluded that a) as a consequence of unspecific interference of plasma particles with the secretin RIA-system only a previous removal of these interfering factors leads to reliable test results; should this pre-requisite be neglected falsely too high results are to be expected; b) plasma secretin rises if there is either hydrochloric acid present in the duodenum or if gastric together with food particles reaches the duodenum; c) at least in the dog there may be different molecular species of secretin circulating in the peripherical plasma, however the biological role of these is unknown at present. (orig./TRV) [de

  10. A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

    Science.gov (United States)

    Fennell, T R; Brown, C D

    2001-06-15

    Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.

  11. Inhaled /sup 239/PuO/sub 2/ and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.; Lauhala, K.E.; Buschbom, R.L.; Hiastala, M.P.; McGee, D.R.; Park, J.F.; Kuffel, E.G.; Ragan, H.A.; Cannon, W.C.; Yaniv, S.S.; Scott, B.R.

    1988-08-01

    Rats and beagle dogs were given doses of /sup 60/Co gamma radiation and/or body burdens of /sup 239/PuO/sub 2/ within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs.

  12. Bone pain caused by swelling of mouse ear capsule static xylene and effects on rat models of cervical spondylosis

    Science.gov (United States)

    Zhang, Xuhui; Xia, Lei; Hao, Shaojun; Chen, Weiliang; Guo, Junyi; Ma, Zhenzhen; Wang, Huamin; Kong, Xuejun; Wang, Hongyu; Zhang, Zhengchen

    2018-04-01

    To observe the effect of intravenous bone pain Capsule on the ear of mice induced by xylene, swelling of rat models of cervical spondylosis. Weighing 18 ˜ 21g 50 mice, male, were randomly divided into for five groups, which were fed with service for bone pain static capsule suspension, Jingfukang granule suspension 0.5%CMC liquid and the same volume of. Respectively to the mice ear drop of xylene 0.05 ml, 4h after cervical dislocation, the mice were sacrificed and the cut two ear, rapid analytical balance weighing, and calculate the ear swelling degree and the other to take the weight of 200 - 60 250g male SD rats, were randomly divided into for 6 groups, 10 rats in each group, of which 5 groups made cervical spondylosis model. Results: with the blank group than bone pain static capsule group and Jingfukang granule group can significantly reduce mouse auricular dimethylbenzene swelling, significantly reduce ear swelling degree (P cervical spondylosis. With the model group ratio, large, medium and small dose of bone pain static capsule group, Jingfukang granule group (P pain static capsule group, Jingfukang granule group can significantly reduce the rat X-ray scores (P pain static capsule can significantly reduce mouse auricular dimethylbenzene swelling. The bone pain capsule has a good effect on the rat model of cervical spondylosis.

  13. Comparison of the subcellular distribution of monomeric 239Pu and 59Fe in the liver of rat, mouse, and Syrian and Chinese hamsters

    International Nuclear Information System (INIS)

    Winter, R.; Seidel, A.

    1982-01-01

    The subcellular distribution of 239 Pu and 59 Fe 10 days after intravenous injection as a citrate complex was investigated by sucrose density gradient centrifugation in the liver of rat, mouse, and Syrian and Chinese hamsters. Lysosomes were separated from other cell constituents by injection of the nonionic detergent Triton WR 1339 4 days before sacrifice. The Triton-induced decrease in the density of the lysosomes was very similar in all four animal species and was followed closely by a corresponding decrease of the median density of the 239 Pu profiles in rat, mouse, and, to a smaller extent, Syrian hamster. However, in Chinese hamster a clear correspondence between lysosomes and 239 Pu was not found 10 days after nuclide injection. It was concluded that lysosomes are the main storage organelles fo 239 Pu in the liver of rat and mouse and that in all four animal species mitochondria and endoplasmic reticulum do not play any significant role in binding the radionuclide. The relevance of pericellular membranes has to be checked. The distribution patterns of 59 Fe and 239 Pu were quite different

  14. Immunologic analyses of mouse cystathionase in normal and leukemic cells

    International Nuclear Information System (INIS)

    Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.

    1978-01-01

    Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

  15. Pharmacokinetics of MMB4 DMS in rats, rabbits, and dogs following a single IV administration.

    Science.gov (United States)

    Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

    2013-01-01

    Organophosphorus (OP) nerve agents pose tremendous threats to both military and civilian populations. The substance 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) is being developed as a replacement for the currently fielded 2-pyridine aldoxime, or pralidoxime (2-PAM) as a treatment for OP nerve agent-induced toxicity. The present study characterized pharmacokinetic (PK) profiles of MMB4 in male and female Sprague-Dawley rats, New Zealand White rabbits, and beagle dogs given a single intravenous (IV) administration of MMB4 dimethanesulfonate (DMS) at 55, 25, and 15 mg/kg dose, respectively. The plasma MMB4 concentration versus time profiles were biphasic for all species tested and fit a 2-compartment model with first-order elimination. There were no overt sex-related differences in the calculated PK parameters. For the rat, rabbit, and dog, the average systemic exposure parameters predicted Cmax (µg/mL) and AUC∞ (µg·h/mL) were 273 and 71.0, 115 and 48.1, and 87.4 and 39.6; the average volume of distribution (mL/kg) values to the central and peripheral compartments were 207 and 143, 242 and 172, and 198 and 213; and the average elimination half-life (hour) and clearance (mL/h/kg) values were 0.18 and 778, 0.29 and 577, and 0.32 and 430, respectively, when the PK parameters for males and females were combined. The current study revealed a similarity in the volume of distribution to the central compartment for MMB4 among the 3 species tested while demonstrating species-related differences in the elimination half-life and clearance of MMB4.

  16. Comparative study on the disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) and dopamine hydrochloride in rats and dogs

    International Nuclear Information System (INIS)

    Yoshikawa, M.; Endo, H.; Otsuka, M.; Yamaguchi, I.; Harigaya, S.

    1988-01-01

    The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA-870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of [ 14 C]TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after [ 14 C]DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of [ 14 C]TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of [ 14 C]TA-870 and 12.6% of the dose of [ 14 C]DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug

  17. Litigation Technical Support and Services, Rocky Mountain Arsenal. Biota Remedial Investigation, Version 3.2. Volume 1

    Science.gov (United States)

    1989-05-01

    significantly. while isodrin is an analog of endrtr and is converted metabolically to that compound. Analyses were also performed for I *l.-dichloro-2,2-bis...abundant are the deer mouse, prairie and meadow voles, and Ord’s kangaroo rat. Larger, more conspicuous rodents include the black-tailed prairie dog...meadow vole, Ord’s kangaroo rat, hispid pocket mouse, and silky pocket mouse(MKE, 1988). Tall weedy forb$, yucca, sand sagebrush, and cattails are

  18. Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells

    Directory of Open Access Journals (Sweden)

    Burgoon Lyle D

    2011-04-01

    Full Text Available Abstract Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared. Results Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches. Conclusions Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

  19. Dog sperm head morphometry: its diversity and evolution

    Directory of Open Access Journals (Sweden)

    Carles Soler

    2017-01-01

    Full Text Available Dogs have been under strong artificial selection as a consequence of their relationship with man. Differences between breeds are evident that could be reflected in seminal characteristics. The present study was to evaluate differences in sperm head morphometry between seven well-defined breeds of dog: the British Bulldog, Chihuahua, German Shepherd, Labrador Retriever, Spanish Mastiff, Staffordshire Terrier, and Valencian Rat Hunting dog. Semen samples were obtained by masturbation and smears stained with Diff-Quik. Morphometric analysis (CASA-Morph produced four size and four shape parameters. Length, Ellipticity, and Elongation showed higher differences between breeds. MANOVA revealed differences among all breeds. Considering the whole dataset, principal component analysis (PCA showed that PC1 was related to head shape and PC2 to size. Procluster analysis showed the British Bulldog to be the most isolated breed, followed by the German Shepherd. The PCA breed by breed showed the Chihuahua, Labrador Retriever, Spanish Mastiff, and Staffordshire Terrier to have PC1 related to shape and PC2 to size, whereas the British Bulldog, Valencia Rat Hunting dog, and German Shepherd had PC1 related to size and PC2 to shape. The dendrogram for cluster groupings and the distance between them showed the British Bulldog to be separated from the rest of the breeds. Future work on dog semen must take into account the large differences in the breeds′ sperm characteristics. The results provide a base for future work on phylogenetic and evolutionary studies of dogs, based on their seminal characteristics.

  20. Dog sperm head morphometry: its diversity and evolution.

    Science.gov (United States)

    Soler, Carles; Alambiaga, Ana; Martí, Maria A; García-Molina, Almudena; Valverde, Anthony; Contell, Jesús; Campos, Marcos

    2017-01-01

    Dogs have been under strong artificial selection as a consequence of their relationship with man. Differences between breeds are evident that could be reflected in seminal characteristics. The present study was to evaluate differences in sperm head morphometry between seven well-defined breeds of dog: the British Bulldog, Chihuahua, German Shepherd, Labrador Retriever, Spanish Mastiff, Staffordshire Terrier, and Valencian Rat Hunting dog. Semen samples were obtained by masturbation and smears stained with Diff-Quik. Morphometric analysis (CASA-Morph) produced four size and four shape parameters. Length, Ellipticity, and Elongation showed higher differences between breeds. MANOVA revealed differences among all breeds. Considering the whole dataset, principal component analysis (PCA) showed that PC1 was related to head shape and PC2 to size. Procluster analysis showed the British Bulldog to be the most isolated breed, followed by the German Shepherd. The PCA breed by breed showed the Chihuahua, Labrador Retriever, Spanish Mastiff, and Staffordshire Terrier to have PC1 related to shape and PC2 to size, whereas the British Bulldog, Valencia Rat Hunting dog, and German Shepherd had PC1 related to size and PC2 to shape. The dendrogram for cluster groupings and the distance between them showed the British Bulldog to be separated from the rest of the breeds. Future work on dog semen must take into account the large differences in the breeds' sperm characteristics. The results provide a base for future work on phylogenetic and evolutionary studies of dogs, based on their seminal characteristics.

  1. Species-specific differences in peroxisome proliferation, catalase, and SOD2 upregulation as well as toxicity in human, mouse, and rat hepatoma cells induced by the explosive and environmental pollutant 2,4,6-trinitrotoluene.

    Science.gov (United States)

    Naumenko, Ekaterina Anatolevna; Ahlemeyer, Barbara; Baumgart-Vogt, Eveline

    2017-03-01

    2,4,6-Trinitrotoluene (TNT) has been widely used as an explosive substance and its toxicity is still of interest as it persisted in polluted areas. TNT is metabolized in hepatocytes which are prone to its toxicity. Since analysis of the human liver or hepatocytes is restricted due to ethical reasons, we investigated the effects of TNT on cell viability, reactive oxygen species (ROS) production, peroxisome proliferation, and antioxidative enzymes in human (HepG2), mouse (Hepa 1-6), and rat (H4IIEC3) hepatoma cell lines. Under control conditions, hepatoma cells of all three species were highly comparable exhibiting identical proliferation rates and distribution of their cell cycle phases. However, we found strong differences in TNT toxicity with the lowest IC 50 values (highest cell death rate) for rat cells, whereas human and mouse cells were three to sevenfold less sensitive. Moreover, a strong decrease in cellular dehydrogenase activity (MTT assay) and increased ROS levels were noted. TNT caused peroxisome proliferation with rat hepatoma cells being most responsive followed by those from mouse and human. Under control conditions, rat cells contained fivefold higher peroxisomal catalase and mitochondrial SOD2 activities and a twofold higher capacity to reduce MTT than human and mouse cells. TNT treatment caused an increase in catalase and SOD2 mRNA and protein levels in human and mouse, but not in rat cells. Similarly, human and mouse cells upregulated SOD2 activity, whereas rat cells failed therein. We conclude that TNT induced oxidative stress, peroxisome proliferation and mitochondrial damage which are highest in rat cells rendering them most susceptible toward TNT. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 989-1006, 2017. © 2016 Wiley Periodicals, Inc.

  2. 78 FR 46274 - Pyroxasulfone; Pesticide Tolerances

    Science.gov (United States)

    2013-07-31

    .... requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA). DATES: This regulation is... pyroxasulfone in mice, rats, and dogs produced a variety of adverse effects in several target organs. Effects... indicators), neurotoxicity characterized by axonal/myelin degeneration in the sciatic nerve (dog, mouse, and...

  3. The Charles River "hairless" rat mutation is distinct from the hairless mouse alleles.

    Science.gov (United States)

    Panteleyev, A A; Christiano, A M

    2001-02-01

    The Charles River (CR) "hairless" rat is one of the autosomal recessive hypotrichotic animal models actively studied in pharmacologic and dermatologic research. Despite its widespread use, the molecular basis of this monogenic mutation remains unknown, and the skin histologic features of this phenotype have never been described. However, the designation "hairless" has been used as an extension of the hairless mouse (hr) nomenclature on the basis of the clinical absence of hairs in both phenotypes. We present a description of the histopathologic changes in heterozygous and homozygous CR hairless rat mutants during the first month of life. The postnatal homozygous rat skin was characterized by abnormal keratinization of the hair shaft and formation of a thick and dense layer of corneocytes in the lower portion of the epidermal stratum corneum. This layer prevented the improperly keratinized hair shaft from penetrating the skin surface. Starting from the latest stages of hair follicle (HF) development, obvious signs of HF degeneration were observed in homozygous skin. This process was extremely rapid, and by day 12, mainly atrophic HFs with abnormal or broken hairs were present in the skin. Therefore, the mutation in the CR rat abrogates cell proliferation in the hair matrix and affects keratinocyte differentiation in the HF and interfollicular epidermis, a phenotype that is completely distinct from hr/hr. To test whether the CR rat harbored a mutation in the hr gene, we analyzed the coding region of this gene and consensus intron splice site sequences in mutant rats and found no mutation, further supporting phenotypic evidence that the hairless phenotype in CR rats is not allelic with hairless. Finally, using intragenic polymorphisms, we were able to exclude homozygosity at the hairless locus by use of genotypic analysis. Thus, morphologic analysis of successive stages of phenotype development in the CR hairless rat, together with definitive molecular studies

  4. Teratology studies in the mouse.

    Science.gov (United States)

    Marsden, Edward; Leroy, Mariline

    2013-01-01

    The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.

  5. Localization of pre- and postsynaptic cholinergic markers in rodent forebrain : A brief history and comparison of rat and mouse

    NARCIS (Netherlands)

    Van der Zee, E. A.; Keijser, J.N.

    2011-01-01

    Rat and mouse models are widely used for studies in cognition and pathophysiology, among others. Here, we sought to determine to what extent these two model species differ for cholinergic and cholinoceptive features. For this purpose, we focused on cholinergic innervation patterns based on choline

  6. Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat

    Directory of Open Access Journals (Sweden)

    Jin Hong

    2009-12-01

    Full Text Available Abstract Background The dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin at the heart of the dystrophin glycoprotein complex in the main clinically affected tissues (skeletal muscle, heart and brain is its distant relative, α-dystrobrevin. The α-dystrobrevin gene is subject to complex transcriptional and post-transcriptional regulation, generating a substantial range of isoforms by alternative promoter use, alternative polyadenylation and alternative splicing. The choice of isoform is understood, amongst other things, to determine the stoichiometry of syntrophins (and their ligands in the dystrophin glycoprotein complex. Results We show here that, contrary to the literature, most α-dystrobrevin genes, including that of humans, encode three distinct syntrophin-binding sites, rather than two, resulting in a greatly enhanced isoform repertoire. We compare in detail the quantitative tissue-specific expression pattern of human and mouse α-dystrobrevin isoforms, and show that two major gene features (the novel syntrophin-binding site-encoding exon and the internal promoter and first exon of brain-specific isoforms α-dystrobrevin-4 and -5 are present in most mammals but specifically ablated in mouse and rat. Conclusion Lineage-specific mutations in the murids mean that the mouse brain has fewer than half of the α-dystrobrevin isoforms found in the human brain. Our finding that there are likely to be fundamental functional differences between the α-dystrobrevins (and therefore the dystrophin glycoprotein complexes of mice and humans raises questions about the current use of the mouse as the principal model animal for studying Duchenne muscular dystrophy and other related disorders, especially the neurological aspects thereof.

  7. Mouse-specific antibody responses to a monoclonal antibody during repeated immunoscintigraphy investigations: Comparison of antibody titres and imaging studies in a rat model

    International Nuclear Information System (INIS)

    Pimm, M.V.; Gribben, S.J.; Markham, A.J.; Perkins, A.C.

    1990-01-01

    As a model for human mouse-specific antibody responses in patients undergoing immunoscintigraphy, we have investigated in rats the production of mouse-specific antibodies (MA) to the mouse monoclonal antibody 791T/36. At intervals of between 5 and 16 weeks the rats were given repeated cycles of intravenous (IV) injections of antibody with or without a simultaneous intradermal (ID) injection. The IV dose was 60 μg/kg, a dose similar to that used in many clinical immunoscintigraphy studies. The ID injection was 2 μg, which mimicks the skin test dose often given in clinical imaging protocols. The study was carried out with both 131 I-labelled antibody and with antibody labelled with 111 In by DTPA chelation. MA was measured with a passive haemagglutination assay using sheep red blood cells coated with the monoclonal antibody. Of rats given ID injections of unlabelled antibody at the same time as the IV imaging doses, 9/20 produced MA during 4 cycles of injections. In contrast, only 2/16 rats given only the IV dose produced MA. Both 131 I- and 111 In-labelled antibody appeared equally immunogenic with 5/18 and 6/18 overall responders, respectively. The production of MA was associated with a significant perturbation in the biodistribution of the IV dose of labelled antibody as seen by gamma-camera imaging of the rats given 111 In-labelled antibody. There was clearance of immune complexes to the liver, this organ accumulating up to 90% of the whole body count rate of radiolabel. MA titres of between 1/100 and 1/78000 caused equal perturbation of biodistribution, although below 1/100 the effect was more variable. (orig.)

  8. Quantification of 2'-deoxy-2'-β-fluoro-4'-azidocytidine in rat and dog plasma using liquid chromatography-quadrupole time-of-flight and liquid chromatography-triple quadrupole mass spectrometry: Application to bioavailability and pharmacokinetic studies.

    Science.gov (United States)

    Peng, Youmei; Cheng, Tiefeng; Dong, Lihong; Zhang, Yuhai; Chen, Xiaojing; Jiang, Jinhua; Zhang, Jingmin; Guo, Xiaohe; Guo, Mintong; Chang, Junbiao; Wang, Qingduan

    2014-09-01

    2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) is a novel pyrimidine analog that inhibits not only the replication of the hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV but also the replication of lamivudine-resistant HBV, 4'-azidocytidine or 2'-β-methylcytidine-resistant HCV, and nucleoside reverse-transcriptase inhibitor-resistant HIV variants. The present study was undertaken to evaluate the absolute oral bioavailability of FNC in rats and the pharmacokinetic properties of FNC after intragastric administration of single and multiple doses in rats and dogs. A sensitive high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) method and a reliable high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC/QqQ MS/MS) method were established for the determination of FNC in the rat and dog plasmas, respectively. The sample preparation involved a protein-precipitation method with methanol after the addition of lamivudine as an internal standard. FNC was analyzed by LC using a YMC-Pack Pro C18 column (150mm×4.6mm, 3μm) with methanol (containing 0.3% formic acid): 10mM ammonium acetate (containing 0.3% formic acid, pH 2.8) (35:65, v/v) as the mobile phase. Both mass spectrometers were equipped with an electrospray ionization interface in the positive-ion mode. The linear range was from 2.00 to 2000.00ngmL(-1) in rat plasma and 0.50 to 400.00ngmL(-1) in dog plasma. The intraday and interday precision were less than 10.55%, and the accuracy was in the range of -5.86 to 5.13%. The mean recoveries were greater than 82.70% and 82.97% for FNC and IS, respectively. The HPLC/Q-TOF MS and HPLC/QqQ MS/MS methods were both successfully applied in the pharmacokinetic studies of FNC in rats and dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Guanfu base A, an antiarrhythmic alkaloid of Aconitum coreanum, Is a CYP2D6 inhibitor of human, monkey, and dog isoforms.

    Science.gov (United States)

    Sun, Jianguo; Peng, Ying; Wu, Hui; Zhang, Xueyuan; Zhong, Yunxi; Xiao, Yanan; Zhang, Fengyi; Qi, Huanhuan; Shang, Lili; Zhu, Jianping; Sun, Yue; Liu, Ke; Liu, Jinghan; A, Jiye; Ho, Rodney J Y; Wang, Guangji

    2015-05-01

    Guanfu base A (GFA) is a novel heterocyclic antiarrhythmic drug isolated from Aconitum coreanum (Lèvl.) rapaics and is currently in a phase IV clinical trial in China. However, no study has investigated the influence of GFA on cytochrome P450 (P450) drug metabolism. We characterized the potency and specificity of GFA CYP2D inhibition based on dextromethorphan O-demethylation, a CYP2D6 probe substrate of activity in human, mouse, rat, dog, and monkey liver microsomes. In addition, (+)-bufuralol 1'-hydroxylation was used as a CYP2D6 probe for the recombinant form (rCYP2D6), 2D1 (rCYP2D1), and 2D2 (rCYP2D2) activities. Results show that GFA is a potent noncompetitive inhibitor of CYP2D6, with inhibition constant Ki = 1.20 ± 0.33 μM in human liver microsomes (HLMs) and Ki = 0.37 ± 0.16 μM for the human recombinant form (rCYP2D6). GFA is also a potent competitive inhibitor of CYP2D in monkey (Ki = 0.38 ± 0.12 μM) and dog (Ki = 2.4 ± 1.3 μM) microsomes. However, GFA has no inhibitory activity on mouse or rat CYP2Ds. GFA did not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but showed slight inhibition of 2B6 and 2E1. Preincubation of HLMs and rCYP2D6 resulted in the inactivation of the enzyme, which was attenuated by GFA or quinidine. Beagle dogs treated intravenously with dextromethorphan (2 mg/ml) after pretreatment with GFA injection showed reduced CYP2D metabolic activity, with the Cmax of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration-time curve half that of the saline-treated group. This study suggests that GFA is a specific CYP2D6 inhibitor that might play a role in CYP2D6 medicated drug-drug interaction. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Oxidative cleavage of the octyl side chain of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045) in rat and dog liver preparations.

    Science.gov (United States)

    Umehara, K; Kudo, S; Hirao, Y; Morita, S; Uchida, M; Odomi, M; Miyamoto, G

    2000-08-01

    The metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a new potent biguanide antiseptic, was investigated using rat and dog liver preparations to elucidate the mechanism of OPB-2045 metabolite formation, in which the octyl side chain is reduced to four, five, or six carbon atoms. Chemical structures of metabolites were characterized by 1H NMR, fast atom bombardment/mass spectrometry, and liquid chromatography/electrospray ionization-tandem mass spectrometry. Three main metabolites were observed during incubation of OPB-2045 with rat liver S9: 2-octanol (M-1), 3-octanol (M-2), and 4-octanol (M-3). In the incubation of OPB-2045 with dog liver S9, eight metabolites were observed, seven of which being M-1, M-2, M-3, 2-octanone (M-4), threo-2,3-octandiol (M-5), erythro-2,3-octandiol (M-6), and 1,2-octandiol (M-7). M-5 and M-6 were further biotransformed to a ketol derivative and C-C bond cleavage metabolite (hexanoic acid derivative), an in vivo end product, in the incubation with dog liver microsomes. The reactions required NADPH as a cofactor and were significantly inhibited by the various inhibitors of cytochrome P450 (i.e., CO, n-octylamine, SKF 525-A, metyrapone, and alpha-naphthoflavone). The results indicate that the degraded products of OPB-2045 are produced by C-C bond cleavage after monohydroxylation, dihydroxylation, and ketol formation at the site of the octyl side chain with possible involvement of cytochrome P450 systems. This aliphatic C-C bond cleavage by sequential oxidative reactions may play an important role in the metabolism of other drugs or endogenous compounds that possess aliphatic chains.

  11. Experimental studies on the scintigraphy of the pancreas in rats and dogs by using isotope labelled dye

    Energy Technology Data Exchange (ETDEWEB)

    Bando, A

    1976-06-01

    Tetraiodo-dye solutions such as eight percent erythrosine B solution, /sup 131/I-erythrosine B solution and /sup 131/I-rose bengal solution were administered to dogs and rats by the intravenous, intraperitoneal, or intramuscular routes. /sup 131/I-rose bengal, when injected by intraperitoneal route, was found to be accumulated more actively in the pancreas, showing a peak concentration per gram of tissue some fifteen times higher than that of the liver, and also significant intrapancreatic deposit of the dye was long sustained, and yielded pancreatic concentrations approximately four to six times of those usually produced by the conventional intravenous injection of /sup 75/Se-selenomethionine.

  12. Activation and detoxification metabolism of urban air pollutants 2-nitrobenzanthrone and carcinogenic 3-nitrobenzanthrone by rat and mouse hepatic microsomes.

    Science.gov (United States)

    Stiborova, Marie; Cechova, Tereza; Borek-Dohalska, Lucie; Moserova, Michaela; Frei, Eva; Schmeiser, Heinz H; Paca, Jan; Arlt, Volker M

    2012-01-01

    2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. Understanding which enzymes are involved in metabolism of these toxicants is important in the assessment of individual susceptibility. Here, metabolism of 2-NBA and 3-NBA by rat and mouse hepatic microsomes containing cytochromes P450 (CYPs), their reductase (NADPH:CYP reductase), and NADH:cytochrome b5 reductase was investigated under anaerobic and aerobic conditions. In addition, using the same microsomal systems, 2-NBA and 3-NBA were evaluated to be enzymatically activated under anaerobic conditions to species generating 2-NBA- and 3-NBA-derived DNA adducts. High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation and characterization of 2-NBA and 3-NBA metabolites formed by hepatic microsomes of rats and mice under the anaerobic and aerobic conditions. Microsomal systems isolated from the liver of the control (untreated) rats and rats pretreated with Sudan I, β-naphthoflavone (β-NF), phenobarbital (PB), ethanol and pregnenolon 16α-carbonitrile (PCN), the inducers of cytochromes P450 (CYP) 1A1, 1A1/2, 2B, 2E1 and 3A, respectively, were used in this study. Microsomes of mouse models, a control mouse line (wild-type, WT) and Hepatic Cytochrome P450 Reductase Null (HRN) mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting this enzyme in their livers, were also employed. To detect and quantify the 2-NBA- and 3-NBA-derived DNA adducts, the 32P postlabeling technique was used. Both reductive metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), found to be formed predominantly under the anaerobic conditions, and two 3-NBA oxidative metabolites, whose structures have not yet been investigated, were formed by several microsomal systems used in the study. Whereas a 3-NBA reductive metabolite

  13. Vitamin D Receptor Expression in Dogs

    Science.gov (United States)

    Gow, A.G.; Milne, E.; Drummond, D.; Smith, S.; Handel, I.; Mellanby, R.J.

    2018-01-01

    Background There is growing evidence linking low blood vitamin D concentration to numerous diseases in people and in dogs. Vitamin D influences cellular function by signaling through the vitamin D receptor (VDR). Little is known about which non‐skeletal tissues express the VDR or how inflammation influences its expression in the dog. Objectives To define which non‐skeletal canine tissues express the VDR and to investigate expression in inflamed small intestine. Animals Thirteen non‐skeletal tissues were collected prospectively from 6 control dogs. Thirty‐five dogs diagnosed with a chronic enteropathy (CE) and 24 control dogs were prospectively enrolled and duodenal biopsies were evaluated for VDR expression. Methods Prospective; blinded assessment of canine intestinal VDR. Dogs with CE were included once other identifiable causes of intestinal disease were excluded. Age matched controls were included with no intestinal clinical signs. VDR expression was assessed immunohistochemically in all samples, using a Rat IgG VDR monoclonal antibody. Quantitative real‐time polymerase chain reaction (qPCR) was also used for duodenal biopsies. Results VDR expression as assessed by immunohistochemistry (IHC) was highest in the kidney, duodenum, skin, ileum and spleen, and weak in the colon, heart, lymph node, liver, lung, and ovary. Gastric and testicular tissue did not express the VDR. There was no statistical difference in duodenal VDR expression between the 24 healthy dogs and 34 dogs with CE when quantified by either qPCR (P = 0.87) or IHC (P = 0.099). Conclusions and Clinical Importance The lack of down regulation of VDR expression in inflamed intestine contrasts with previous studies in humans. Our findings support future studies to investigate whether vitamin D and its analogues can be used to modulate intestinal inflammation in the dog. PMID:29469965

  14. Use of intraperitoneal xenon-133 for imaging of intestinal strangulation in small bowel obstruction. [Rats; Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Bulkley, G.B.; Gharagozloo, F.; Alderson, P.O.; Horn, S.D.; Zuidema, G.D.

    1981-01-01

    Intraperitoneal xenon-133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay inexternally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponsed to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction.

  15. Specific tolerance induction across a xenogeneic barrier: Production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

    International Nuclear Information System (INIS)

    Sharabi, Y.; Aksentijevich, I.; Sundt, T.M. III; Sachs, D.H.; Sykes, M.

    1990-01-01

    The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipients with monoclonal antibodies (mAbs) against NK1.1, Thy-1.2, CD4 and CD8, followed by administration of 3 Gy whole body radiation (WBI), 7 Gy thymic irradiation, and infusion of T cell-depleted rat bone marrow cells (BMC). Rat cells appeared among peripheral blood lymphocytes (PBL) of such recipients by 2-3 wk, and rat T cells by 2-5 wk following bone marrow transplantation (BMT). Donor-type rat skin grafts placed 4 mo after BMT were accepted, while simultaneously placed non-donor-type rat skin grafts were promptly rejected. In addition to its clinical potential, the ability to induce donor-specific tolerance across xenogeneic barriers using such a nonlethal preparative regimen provides a valuable model for the study of mechanisms of xenogeneic transplantation tolerance

  16. Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells.

    Science.gov (United States)

    Krijt, J; van Holsteijn, I; Hassing, I; Vokurka, M; Blaauboer, B J

    1993-01-01

    The effects of the herbicides fomesafen, oxyfluorfen, oxadiazon and fluazifop-butyl on porphyrin accumulation in mouse liver, rat primary hepatocyte culture and HepG2 cells were investigated. Ten days of herbicide feeding (0.25% in the diet) increased the liver porphyrins in male C57B1/6J mice from 1.4 +/- 0.6 to 4.8 +/- 2.1 (fomesafen) 16.9 +2- 2.9 (oxyfluorfen) and 25.9 +/- 3.1 (oxadiazon) nmol/g wet weight, respectively. Fluazifop-butyl had no effect on liver porphyrin metabolism. Fomesafen, oxyfluorfen and oxadiazon increased the cellular porphyrin content of rat hepatocytes after 24 h of incubation (control, 3.2 pmol/mg protein, fomesafen, oxyfluorfen and oxadiazon at 0.125 mM concentration 51.5, 54.3 and 44.0 pmol/mg protein, respectively). The porphyrin content of HepG2 cells increased from 1.6 to 18.2, 10.6 and 9.2 pmol/mg protein after 24 h incubation with the three herbicides. Fluazifop-butyl increased hepatic cytochrome P450 levels and ethoxy- and pentoxyresorufin O-dealkylase (EROD and PROD) activity, oxyfluorfen increased PROD activity. Peroxisomal palmitoyl CoA oxidation increased after fomesafen and fluazifop treatment to about 500% of control values both in mouse liver and rat hepatocytes. Both rat hepatocytes and HepG2 cells can be used as a test system for the porphyrogenic potential of photobleaching herbicides.

  17. Effects of strontium malonate (NB S101) on the compositional, structural and biomechanical properties of calcified tissues in rats and dogs

    DEFF Research Database (Denmark)

    Raffalt, Anders Christer

    animal studies: 1) a 4-week study in dogs using SrM doses of 0 (control), 300, 1000 and 3000 mg kg-1 day-1, 2) a 26-week study in rats, and 3) a 52-week study in dogs, both using SrM doses of 0 (control), 100, 300 and 1000 mg kg-1 day-1. Femurs, vertebrae, skullcaps and teeth from the treated animals...... were examined for treatment-related changes in concentrations of Sr, Ca, Mg and P using inductively coupled mass spectrometry (ICP-MS). Bone mineral density (BMD) was determined using dual energy X-ray absorptiometry (DEXA), and the biomechanical properties of the bones were assessed using bending...... and compression tests. A procedure was developed for determination of Mg, P, Ca and Sr in diluted serum using ICP-MS in combination with an Apex-Q desolvation unit. The Apex inlet system reduced the generation of oxides in the ICP and improved the sensitivity for Sr by a factor of 14 compared with a conventional...

  18. Resistance to plague among black-tailed prairie dog populations

    Science.gov (United States)

    Rocke, Tonie E.; Williamson, Judy; Cobble, Kacy R.; Busch, Joseph D.; Antolin, Michael F.; Wagner, David M.

    2012-01-01

    In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (pdogs were quite similar in their response, with overall survival rates of 50% and 60%, respectively. Prairie dogs from these states were heterogenous in their response, with some animals dying at the lowest dose (37% and 20%, respectively) and some surviving even at the highest dose (29% and 40%, respectively). Microsatellite analysis revealed that all three groups were distinct genetically, but further studies are needed to establish a genetic basis for the observed differences in plague resistance.

  19. Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co-cultures of rat, dog, and human tissues

    International Nuclear Information System (INIS)

    Vickers, Alison E.M.; Sinclair, John R.; Fisher, Robyn L.; Morris, Stephen R.; Way, William

    2010-01-01

    A novel in vitro model to investigate time-dependent and concentration-dependent responses in blood cells and hemolytic events is studied for rat, dog, and human tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole (MMI) was selected as a reference compound, since metabolism of its imidazole thione moiety is linked with hematologic disorders and hepatotoxicity. An oxidative stress response occurred in all three species, marked by a decline in blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred at high MMI concentrations in the presence of a liver slice with rat (≥ 1000 μM at 48 h) and human tissues (≥ 1000 μM at 48 h, ≥ 750 μM at 72 h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but minimal to no hemolysis. The up-regulation of liver genes for heme degradation (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and utilization (mGST1 and Gclc) were early markers of the oxidative stress response. The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a response to damaged red blood cells, and Hp (haptoglobin) up-regulation is indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8 gene expression suggested an activation of an inflammatory response by liver endothelial cells. In summary, MMI exposure led to an oxidative stress response in blood cells, and an up-regulation of liver genes involved with oxidative stress and heme homeostasis, which was clearly separate and preceded frank hemolysis.

  20. Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

    Science.gov (United States)

    Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

    2012-11-01

    Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

  1. Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

    Science.gov (United States)

    Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

    2010-06-01

    Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

  2. RatMap--rat genome tools and data.

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

  3. RatMap—rat genome tools and data

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

  4. Comparison of the permeability of metoprolol and labetalol in rat, mouse, and Caco-2 cells: use as a reference standard for BCS classification.

    Science.gov (United States)

    Incecayir, Tuba; Tsume, Yasuhiro; Amidon, Gordon L

    2013-03-04

    The purpose of this study was to investigate labetalol as a potential high permeability reference standard for the application of Biopharmaceutics Classification Systems (BCS). Permeabilities of labetalol and metoprolol were investigated in animal intestinal perfusion models and Caco-2 cell monolayers. After isolating specific intestinal segments, in situ single-pass intestinal perfusions (SPIP) were performed in rats and mice. The effective permeabilities (Peff) of labetalol and metoprolol, an FDA standard for the low/high Peff class boundary, were investigated in two different segments of rat intestine (proximal jejunum and distal ileum) and in the proximal jejunum of mouse. No significant difference was found between Peff of metoprolol and labetalol in the jejunum and ileum of rat (0.33 ± 0.11 × 10(-4) vs 0.38 ± 0.06 × 10(-4) and 0.57 ± 0.17 × 10(-4) vs 0.64 ± 0.30 × 10(-4) cm/s, respectively) and in the jejunum of mouse (0.55 ± 0.05 × 10(-4) vs 0.59 ± 0.13 × 10(-4) cm/s). However, Peff of metoprolol and labetalol were 1.7 and 1.6 times higher in the jejunum of mouse, compared to the jejunum of rat, respectively. Metoprolol and labetalol showed segmental-dependent permeability through the rat intestine, with increased Peff in the distal ileum in comparison to the proximal jejunum. Most significantly, Peff of labetalol was found to be concentration-dependent. Decreasing concentrations of labetalol in the perfusate resulted in decreased Peff compared to Peff of metoprolol. The intestinal epithelial permeability of labetalol was lower than that of metoprolol in Caco-2 cells at both apical pH 6.5 and 7.5 (5.96 ± 1.96 × 10(-6) vs 9.44 ± 3.44 × 10(-6) and 15.9 ± 2.2 × 10(-6) vs 23.2 ± 7.1 × 10(-6) cm/s, respectively). Labetalol exhibited higher permeability in basolateral to apical (BL-AP) compared to AP-BL direction in Caco-2 cells at 0.1 times the highest dose strength (HDS) (46.7 ± 6.5 × 10(-6) vs 14.2 ± 1.5 × 10(-6) cm/s). The P

  5. Application of a UPLC–MS/MS method to the protein binding study of TM-2 in rat, human and beagle dog plasma

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2016-02-01

    Full Text Available TM-2 known as a potential antitumor drug is a novel semi-synthetic taxane derivative. As drug–protein interactions contribute to insights into pharmacokinetic and pharmacodynamic properties, we elucidated the binding of TM-2 to plasma protein. In this study, a simple, rapid and reliable method was developed and validated employing equilibrium dialysis for the separation of bound and unbound drugs and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS for the quantitation. Protein binding reached equilibrium within 24 h of incubation at 37 °C. After liquid–liquid extraction with methyl tert-butyl ether, the samples were separated on Thermo Syncronis UPLC® C18 (2.1 mm×50 mm, 1.7 µm, and acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM mode via positive electrospray ionization. The assay was linear over the concentration rang of 5–2000 ng/mL. The intra- and inter-day precisions were 0.1%–14.8%, and the accuracy was from −6.4% to 7.0%. This assay has been successfully applied to a protein binding study of TM-2 in rat, human and beagle dog plasma. TM-2 showed high protein binding of 81.4%±6.5% (rat, 87.9%±3.6% (human and 79.4%±4.0% (beagle dog. The results revealed that there was an insignificant difference among the three species.

  6. Dose patterns for 106RuO4 inhaled by Fischer-344 rats and Beagle dogs

    International Nuclear Information System (INIS)

    Runkle, G.E.; Snipes, M.B.

    1978-01-01

    Ruthenium-106 is an abundant fission product radionuclide in the nuclear fuel cycle which has potential for release as ruthenium tetroxide. Ruthenium tetroxide is a vapor, diffuses rapidly through air and porous materials, is chemically reactive and is rapidly reduced by any organic material to the dioxide form. Current ICRP recommendations consider the lung and gastrointestinal tract as critical organs for inhaled particles of radioactive ruthenium. This study was designed to provide additional data needed to adequately assess the risk for humans potentially exposed to 106 Ru encountered in this vapor form. Fischer-344 rats and Beagle dogs were given a nose-only exposure to 106 RuO 4 vapor to determine its distribution and retention patterns. The largest percentage of the initial body burden was found in the nasopharyngeal region of the respiratory tract. Less than 1% of the initial body burden was deposited in the pulmonary region. Most of the 106 Ru was cleared via the feces. A biomathematical simulation model was developed to fit the tissue and excreta data from the rat. This model was used to assess the short-term and long-term risks after inhalation of 106 RuO 4 . The observed deposition, retention and dose patterns for ruthenium tetroxide indicate the nasopharyngeal region should be considered as a critical region when considering the consequences of human exposure to this vapor

  7. Passive Immunization of Anti bZP3 (Zone Pellucida3 in Wistar Rat (Rattus novergicus and Mouse (Mus musculus

    Directory of Open Access Journals (Sweden)

    Y. Pantiwati

    2012-12-01

    Full Text Available This study was aimed at comparing the influence of anti bZP3’s passive immunization on anti-anti bZP3’s titer and pregnancy level on Wistar rats and mice. This study employed factorial design experiment with completely randomized design. The first factor was immunogenic type. The treated rats were immunized with 100 L anti bZP3 in 100 L Complete Freund’s Adjuvant (CFA, while the treated mice were injected with 50 L anti bZP3 in 50 L CFA. Control Wistar rats and mice were immunized with CFA and Incomplete Freund’s Adjuvant (IFA without anti bZP3. The second factor was animal type. The third factor was the length of serum incubation, i.e. 38, 49, 63, 86, 100, and 126 d. Dot blot on the treated Wistar rats and mice showed positive response proven by blue gradation; pre-immune mice as well as control Wistar rats and mice showed negative response proven by white gradation. The highest antibody titer in treated mouse serum was shown in 63 d incubation. The pregnancy on treated mice, control mice and Wistar rat occurred 100% until day 126; while the failure percentage on the treated mice was 4.5%. The pregnancy on treated mice occurred in 86 d incubation (1 rat, 100 d incubation (1 rat, and 126 d incubation (3 rats. Effective passive immunization on similar hospes occurred until day 63; while different hospes was ineffective. Antibodi anti-bZP3 was potential as a contraception through passive immunization on similar hospes.

  8. [Effect of Dendrobium officinale granule on long-term-alcohol-induced hypertension rats].

    Science.gov (United States)

    Lv, Gui-Yuan; Xia, Chao-Qun; Chen, Su-Hong; Su, Jie; Liu, Xiao-Pang; Li, Bo; Gao, Jian-Li

    2013-10-01

    To observe the effect of Dendrobium officinale granule (DOG) on symptoms, blood pressure and serum biochemical indexes of long-term-alcohol-induced hypertension rats. The alcohol-induced hypertension rat model was established by feeding alcohol drink to normal rats (the alcohol volume fraction increases from 5% to 22%). Since the 4th week, DOG was administered for 32 weeks, once everyday. During the experiment, body weight, kinematic parameters (locomotor activities, grip strength, duration of vertigo) and blood pressures (systolic blood pressure, diastolic blood pressure and mean blood pressure) were detected regularly. On the 28th and 32nd weeks, blood samples were collected to determine serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr), cholesterol (CH) and triglycerides (TG). (1) Sign: The DOG-administered group showed reduction in the duration of vertigo and increase in appetite, body weight, locomotor activities and grip strength. (2) Blood pressure: The DOG-administered group showed significant decrease in blood pressure since the 8th week. (3) Biochemical indexes: The DOG-administered group showed notable decrease in serum ALT, AST, ALP, Cr, UA, TG level, but without significant change in TC level. The long-term administration of DOG can relieve alcohol-induced hypertension, while alleviating general signs, liver and kidney injuries and abnormal blood fat biochemical indexes.

  9. Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

    1995-12-01

    Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region.

  10. Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

    International Nuclear Information System (INIS)

    Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

    1995-01-01

    Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region

  11. Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E B; Poulsen, F R; Zimmer, J

    1995-01-01

    Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo....... Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need...

  12. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P L; Hadi, Mackenzie; Laarakkers, Coby M M; Masereeuw, R.|info:eu-repo/dai/nl/155644033; Groothuis, Geny M M; Russel, Frans G M

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker

  13. Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

    Directory of Open Access Journals (Sweden)

    Andrade A.Q.

    2002-01-01

    Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

  14. [Replacement of dogs as research animals for the approval testing of plant protection products].

    Science.gov (United States)

    Box, Rainer J

    2006-01-01

    The replacement of animal testing using dogs for the registration of plant protection products requires a long-term step-by-step procedure. The first goal should be to achieve international agreement on using only one single study in dogs. This would result in a significant short-term reduction of the use of dogs for this purpose. The competent working groups both in the EU and the United States EPA have declared this to be their intended aim. In this context, the 90-day study is to be the preferred study from the scientific as well as the animal welfare points of view. It is proposed to set up an international expert task force within the next 12 months, which should seek to initiate a process of international harmonization of the testing requirements following the example of the International Conference of Harmonization of Technical Requirements for Medical Products, ICH. The goal should be to achieve international agreement on only one single study with dogs within the next 2 to 3 years. In addition, other valid scientific procedures, with which the use of dogs for testing can be reduced, should be critically assessed. A complete replacement of the use of dogs for plant protection product testing is suggested to take place at a later stage. This may be achieved by either deriving safety threshold values by applying a safety factor to chronic NOAEL values obtained in studies using rats for those groups of substances, for which there is evidence that the dog is the more sensitive species, or by combining the chronic rat study with other animal tests stipulated for the registration of pesticides.

  15. Evaluation of antiemetic activities of alcoholic extract of grewia asiatica in experimental model dog

    International Nuclear Information System (INIS)

    Yaqeen, Z.; Shail, T.; Rahman, A.U.; Saleem, M.

    2008-01-01

    The fruits of Grewia asiatica were evaluated for the antiemetic activity in the experimental model dogs, whereas, acute oral toxicity test was carried out in mice and rats. Maximum oral dose of 200 mg/kg and 600 mg/kg of crude alcoholic extract was found non toxic in mice and rats. Oral dose of crude alcoholic extract (120 mg/kg body weight) caused antiemetic effect in dogs in 3 h and controlled emesis centrally induced by Apomorphine (0.044 mg/kg body weight). This activity of G asiatica was comparable with standard commercial anti-emctic drugs like Maxolon (Metoclopramide) and Largactil tablets 10 mg (Chlorpromazine) of M/s. Aventis Pharma., Pakistan. (author)

  16. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    Science.gov (United States)

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    Science.gov (United States)

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  18. Dogs cloned from adult somatic cells.

    Science.gov (United States)

    Lee, Byeong Chun; Kim, Min Kyu; Jang, Goo; Oh, Hyun Ju; Yuda, Fibrianto; Kim, Hye Jin; Hossein, M Shamim; Shamim, M Hossein; Kim, Jung Ju; Kang, Sung Keun; Schatten, Gerald; Hwang, Woo Suk

    2005-08-04

    Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.

  19. Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin.

    Science.gov (United States)

    Bogdanffy, Matthew S; Stachlewitz, Robert F; van Tongeren, Susan; Knight, Brian; Sharp, Dale E; Ku, Warren; Hart, Susan Emeigh; Blanchard, Kerry

    2014-01-01

    Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin. © The Author(s) 2014.

  20. Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

    Science.gov (United States)

    Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

    2016-07-01

    Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    OpenAIRE

    Jie Li; Jie Li; Jie Li; Xin Li; Xin Li; Xin Li; Yu-Shan Ren; Yu-Shan Ren; Yuan-Yuan Lv; Yuan-Yuan Lv; Yuan-Yuan Lv; Jun-Sheng Zhang; Jun-Sheng Zhang; Jun-Sheng Zhang; Xiao-Li Xu

    2017-01-01

    Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including ...

  2. Role of the domestic dog as a reservoir host of Leishmania donovani in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Schallig Henk DFH

    2009-06-01

    Full Text Available Abstract Background The study aims to determine the role of domestic dogs in transmission of visceral leishmaniasis in eastern Sudan. A cross-sectional survey was conducted in 10 villages along the River Rahad in eastern Sudan to elucidate the role of domestic dogs (Canis familiaris, Linnaeus, 1758 as a reservoir host of Leishmania donovani. In this study, 87 dogs were screened for infection by Leishmania donovani. Blood and lymph node samples were taken from 87 and 33 dogs respectively and subsequently screened by the Polymerase Chain Reaction (PCR and Direct Agglutination Test (DAT test. Additional lymph node smears were processed for microscopy and parasite culture. Host preference of the visceral leishmaniasis (VL vector in the area, Phlebotomus orientalis, and other sandflies for the Nile rat (Arvicanthis niloticus, É. Geoffrey, 1803, the genet (Genetta genetta, Linnaeus, 1758, the mongoose (Herpeistes ichneumon, Linnaeus, 1758, and the domestic dog were determined by counting numbers of sand flies attracted to CDC traps that were baited by these animals. Results DAT on blood samples detected anti-Leishmania antibodies in 6 samples (6.9%. Two out of 87 (2.3% blood samples tested were PCR positive, giving an amplification product of 560 bp. The two positive samples by PCR were also positive by DAT. However, none of the 33 lymph nodes aspirates were Leishmania positive when screened by microscopy, culture and genus-specific PCR. The dog-baited trap significantly attracted the highest number of P. orientalis and sand fly species (P Conclusion It is concluded that the results obtained from host attraction studies indicate that dog is more attractive for P. orientalis than Egyptian mongoose, common genet and Nile rat.

  3. Suppression of mouse-killing in rats following irradiation

    International Nuclear Information System (INIS)

    O'Boyle, M.

    1976-01-01

    Suppression of mouse-killing was produced following pairings of mouse-presentations (CS) with 96 roentgens of ionizing radiation (US) at 0 (less than 2 min.) and 30 min. US-CS interstimulus intervals. No suppression was found at CS-US intervals of 30 min., 1 hr., and 2 hr., or at US-CS intervals of 1 hr. and 2 hr

  4. Role of vegetative nervous system in regulation of excretory function of irradiated dog stomach

    International Nuclear Information System (INIS)

    Kostesha, N.Ya.

    1989-01-01

    Dogs and rats were exposed to γ/neutron- and X-radiation. The anterior part of dog's stomach was exposed to 10 Gy and 13 Gy respectively; rats were subjected to whole-body irradiation with absolutely lethal doses. Prior to irradiation, various parts of the vegetative nervous system of both types of animals were switched off pharmocologically. In addition to clinical investigation of radiation sickness the excretory function of the stomach was studied by the excretion of intravenously injected neutral red. The switching-off of the parasympathetic nervous system prior to irradiation stabilized the excretory processes in the stomach, increased the resistance of animals, and, vice wersa, the switching-off of the sympathetic nervous system destabilized the excetory processes and decreased the resistance of the organism

  5. Interspecies Variation of In Vitro Stability and Metabolic Diversity of YZG-331, a Promising Sedative-Hypnotic Compound

    Directory of Open Access Journals (Sweden)

    Zhihao Liu

    2017-08-01

    Full Text Available YZG-331, a synthetic adenosine derivative, express the sedative and hypnotic effects via binding to the adenosine receptor. The current study was taken to investigate the metabolic pathway of YZG-331 as well as species-specific differences in vitro. YZG-331 was reduced by 14, 11, 6, 46, and 11% within 120 min incubation in human, monkey, dog, rat, and mouse liver microsomes (LMs, respectively. However, YZG-331 was stable in human, monkey, dog, rat, and mouse liver cytoplasm. In addition, YZG-331 was unstable in rat or mouse gut microbiota with more than 50% of prototype drug degraded within 120 min incubation. Interestingly, the systemic exposure of M2 and M3 in rats and mice treated with antibiotics were significantly decreased in the pseudo germ-free group. YZG-331 could be metabolized in rat and human liver under the catalysis of CYP enzymes, and the metabolism showed species variation. In addition, 3 phase I metabolites were identified via hydroxyl (M1, hydrolysis (M2, or hydrolysis/ hydroxyl (M3 pathway. Flavin-containing monooxygenase 1 (FMO1 and FMO3 participated in the conversion of YZG-331 in rat LMs. Nevertheless, YZG-331 expressed stability with recombinant human FMOs, which further confirmed the species variation in the metabolism. Overall, these studies suggested that YZG-331 is not stable in LMs and gut microbiota. CYP450 enzymes and FMOs mediated the metabolism of YZG-331, and the metabolic pathway showed species difference. Special attention must be paid when extrapolating data from other species to humans.

  6. Genetic Characterization of Dog Personality Traits.

    Science.gov (United States)

    Ilska, Joanna; Haskell, Marie J; Blott, Sarah C; Sánchez-Molano, Enrique; Polgar, Zita; Lofgren, Sarah E; Clements, Dylan N; Wiener, Pamela

    2017-06-01

    The genetic architecture of behavioral traits in dogs is of great interest to owners, breeders, and professionals involved in animal welfare, as well as to scientists studying the genetics of animal (including human) behavior. The genetic component of dog behavior is supported by between-breed differences and some evidence of within-breed variation. However, it is a challenge to gather sufficiently large datasets to dissect the genetic basis of complex traits such as behavior, which are both time-consuming and logistically difficult to measure, and known to be influenced by nongenetic factors. In this study, we exploited the knowledge that owners have of their dogs to generate a large dataset of personality traits in Labrador Retrievers. While accounting for key environmental factors, we demonstrate that genetic variance can be detected for dog personality traits assessed using questionnaire data. We identified substantial genetic variance for several traits, including fetching tendency and fear of loud noises, while other traits revealed negligibly small heritabilities. Genetic correlations were also estimated between traits; however, due to fairly large SEs, only a handful of trait pairs yielded statistically significant estimates. Genomic analyses indicated that these traits are mainly polygenic, such that individual genomic regions have small effects, and suggested chromosomal associations for six of the traits. The polygenic nature of these traits is consistent with previous behavioral genetics studies in other species, for example in mouse, and confirms that large datasets are required to quantify the genetic variance and to identify the individual genes that influence behavioral traits. Copyright © 2017 by the Genetics Society of America.

  7. A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis.

    Directory of Open Access Journals (Sweden)

    Erin N McDowell

    Full Text Available Fetal testis steroidogenesis plays an important role in the reproductive development of the male fetus. While regulators of certain aspects of steroidogenesis are known, the initial driver of steroidogenesis in the human and rodent fetal testis is unclear. Through comparative analysis of rodent fetal testis microarray datasets, 54 candidate fetal Leydig cell-specific genes were identified. Fetal mouse testis interstitial expression of a subset of these genes with unknown expression (Crhr1, Gramd1b, Itih5, Vgll3, and Vsnl1 was verified by whole-mount in situ hybridization. Among the candidate fetal Leydig cell-specific factors, three receptors (CRHR1, PRLR, and PROKR2 were tested for a steroidogenic function using ex vivo fetal testes treated with receptor agonists (CRH, PRL, and PROK2. While PRL and PROK2 had no effect, CRH, at low (approximately 1 to 10 nM concentration, increased expression of the steroidogenic genes Cyp11a1, Cyp17a1, Scarb1, and Star in GD15 mouse and GD17 rat testes, and in conjunction, testosterone production was increased. Exposure of GD15 fetal mouse testis to a specific CRHR1 antagonist blunted the CRH-induced steroidogenic gene expression and testosterone responses. Similar to ex vivo rodent fetal testes, ≥ 10 nM CRH exposure of MA-10 Leydig cells increased steroidogenic pathway mRNA and progesterone levels, showing CRH can enhance steroidogenesis by directly targeting Leydig cells. Crh mRNA expression was observed in rodent fetal hypothalamus, and CRH peptide was detected in rodent amniotic fluid. Together, these data provide a resource for discovering factors controlling fetal Leydig cell biology and suggest that CRHR1 activation by CRH stimulates rat and mouse fetal Leydig cell steroidogenesis in vivo.

  8. Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s).

    Science.gov (United States)

    Miyamoto, J; Kaneko, H; Takamatsu, Y

    1986-06-01

    In accordance with in vivo findings, of the four chiral isomers of fenvalerate (S-5602 Sumicidin, Pydrin, [RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-chlorophenyl)isovalerate), only the [2R, alpha S]-isomer (B-isomer) yielded cholesteryl [2R]-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) in the in vitro study using several tissue homogenates of mice, rats, dogs, and monkeys. There were species differences in the extent of CPIA-cholesterol-ester formation, with mouse tissues showing relatively higher activity than those of other animals. The kidney, brain, and spleen of mice showed relatively higher capacities to form this ester compared to other tissues, and the enzyme activity was mainly localized in microsomal fractions. The CPIA-cholesterol ester did not seem to be produced by three known biosynthetic pathways of endogenous cholesterol esters--acyl-CoA:cholesterol O-acyltransferase (ACAT), lecithin:cholesterol O-acyltransferase (LCAT), and cholesterol esterase. Carboxyesterase(s) of mouse kidney microsomes solubilized by digitonin hydrolyzed only the B alpha-isomer of fenvalerate, yielding CPIA, whereas they yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. Thus, it appears that the stereoselective formation of the CPIA-cholesterol ester results from the stereoselective formation of the CPIA-carboxyesterase complex only from the B alpha-isomer, which subsequently undergoes cleavage by cholesterol to yield the CPIA-cholesterol ester.

  9. DNA damage in mouse and rat liver by caprolactam and benzoin, evaluated with three different methods.

    Science.gov (United States)

    Parodi, S; Abelmoschi, M L; Balbi, C; De Angeli, M T; Pala, M; Russo, P; Taningher, M; Santi, L

    1989-11-01

    Benzoin and caprolactam were examined for their capability of inducing alkaline DNA fragmentation in mouse and rat liver DNA after treatment in vivo. Three different methods were used. With the alkaline elution technique we measured an effect presumably related to the conformation of the DNA coil. With a viscometric and a fluorometric unwinding method we measured an effect presumably related to the number of unwinding points in DNA. For both compounds only the alkaline elution technique was clearly positive. The results suggest that both caprolactam and benzoin can induce an important change in the conformation of the DNA coil without inducing true breaks in DNA.

  10. Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

    Science.gov (United States)

    Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

    2017-03-01

    The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

  11. Hepatobiliary Clearance Prediction: Species Scaling From Monkey, Dog, and Rat, and In Vitro-In Vivo Extrapolation of Sandwich-Cultured Human Hepatocytes Using 17 Drugs.

    Science.gov (United States)

    Kimoto, Emi; Bi, Yi-An; Kosa, Rachel E; Tremaine, Larry M; Varma, Manthena V S

    2017-09-01

    Hepatobiliary elimination can be a major clearance pathway dictating the pharmacokinetics of drugs. Here, we first compared the dose eliminated in bile in preclinical species (monkey, dog, and rat) with that in human and further evaluated single-species scaling (SSS) to predict human hepatobiliary clearance. Six compounds dosed in bile duct-cannulated (BDC) monkeys showed biliary excretion comparable to human; and the SSS of hepatobiliary clearance with plasma fraction unbound correction yielded reasonable predictions (within 3-fold). Although dog SSS also showed reasonable predictions, rat overpredicted hepatobiliary clearance for 13 of 24 compounds. Second, we evaluated the translatability of in vitro sandwich-cultured human hepatocytes (SCHHs) to predict human hepatobiliary clearance for 17 drugs. For drugs with no significant active uptake in SCHH studies (i.e., with or without rifamycin SV), measured intrinsic biliary clearance was directly scalable with good predictability (absolute average fold error [AAFE] = 1.6). Drugs showing significant active uptake in SCHH, however, showed improved predictability when scaled based on extended clearance term (AAFE = 2.0), which incorporated sinusoidal uptake along with a global scaling factor for active uptake and the canalicular efflux clearance. In conclusion, SCHH is a useful tool to predict human hepatobiliary clearance, whereas BDC monkey model may provide further confidence in the prospective predictions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Public Perceptions of Service Dogs, Emotional Support Dogs, and Therapy Dogs.

    Science.gov (United States)

    Schoenfeld-Tacher, Regina; Hellyer, Peter; Cheung, Louana; Kogan, Lori

    2017-06-15

    As service dogs, emotional support dogs, and therapy dogs have become more prevalent in the USA, so too has the controversy surrounding their legitimacy. Yet, there is a lack of objective data regarding the public's understanding of the role played by each of these types of animals, as well as their perceptions regarding the legitimacy of their integration. An anonymous, online survey was distributed to examine the perceptions of US adults who do not own any type of assistance animal. A total of 505 individuals responded to the online survey, yielding 284 usable responses. Results suggest widespread misconceptions about definitions, rules, regulations, and rights associated with each type of assistance dog. In general, service dogs are more likely to be perceived as helping with a legitimate need, and their access to public spaces is viewed favorably. While there are some concerns about the legitimacy and necessary access rights for emotional support dogs, members of the public correctly identified the roles and rights of therapy dogs. Despite the media's focus on abuses and false representation of these dogs, most participants reported feeling the majority of people are not taking advantage of the system.

  13. Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

    Science.gov (United States)

    Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

  14. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  15. High detection rate of dog circovirus in diarrheal dogs.

    Science.gov (United States)

    Hsu, Han-Siang; Lin, Ting-Han; Wu, Hung-Yi; Lin, Lee-Shuan; Chung, Cheng-Shu; Chiou, Ming-Tang; Lin, Chao-Nan

    2016-06-17

    Diarrhea is one of the most common clinical symptoms reported in companion animal clinics. Dog circovirus (DogCV) is a new mammalian circovirus that is considered to be a cause of alimentary syndromes such as diarrhea, vomiting and hemorrhagic enteritis. DogCV has previously only been identified in the United States, Italy, Germany (GeneBank accession number: KF887949) and China (GeneBank accession number: KT946839). Therefore, the aims of this study were to determine the prevalence of DogCV in Taiwan and to explore the correlation between diarrhea and DogCV infection. Clinical specimens were collected between 2012 and 2014 from 207 dogs suffering from diarrhea and 160 healthy dogs. In this study, we developed a sensitive and specific SYBR Green-based real-time PCR assays to detected DogCV in naturally infected animals. Of the analyzed fecal samples from diarrheal dogs and health dogs, 58 (28.0 %) and 19 (11.9 %), respectively, were DogCV positive. The difference in DogCV prevalence was highly significant (P = 0.0002755) in diarrheal dogs. This is the first study to reveal that DogCV is currently circulating in domestic dogs in Taiwan and to demonstrate its high detection rate in dogs with diarrhea.

  16. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.

    Science.gov (United States)

    Azpurua, Jorge; Ke, Zhonghe; Chen, Iris X; Zhang, Quanwei; Ermolenko, Dmitri N; Zhang, Zhengdong D; Gorbunova, Vera; Seluanov, Andrei

    2013-10-22

    The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

  17. An update on the mouse liver proteome

    Directory of Open Access Journals (Sweden)

    Borlak Jürgen

    2009-09-01

    Full Text Available Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 DE at two different pH ranges, notably 5-8 and 7-10. Based on 9600 in gel digests a total of 643 mouse liver proteins with high sequence coverage (> 20 peptides per protein could be identified by MALDI-TOF-MS peptide mass finger printing. Notably, 255 proteins are novel and have not been reported so far by conventional two-dimensional electrophoresis proteome mapping. Additionally, the results of the present findings for mouse liver were compared to published data of the rat proteome to compile as many proteins as possible in a rodent liver database. Conclusion Based on 2-DE MALDI-TOF-MS a significantly improved proteome map of mouse liver was obtained. We discuss some prominent members of newly identified proteins for a better understanding of liver biology.

  18. A lab-on-a-chip-based multiplex platform to detect potential fraud of introducing pig, dog, cat, rat and monkey meat into the food chain.

    Science.gov (United States)

    Razzak, Md Abdur; Hamid, Sharifah Bee Abd; Ali, Md Eaqub

    2015-01-01

    Food forgery has posed considerable risk to public health, religious rituals, personal budget and wildlife. Pig, dog, cat, rat and monkey meat are restricted in most religions, but their sporadic adulteration are rampant. Market controllers need a low-cost but reliable technique to track and trace suspected species in the food chain. Considering the need, here we documented a lab-on-a-chip-based multiplex polymerase chain reaction (PCR) assay for the authentication of five non-halal meat species in foods. Using species-specific primers, 172, 163, 141, 129 and 108-bp sites of mitochondrial ND5, ATPase 6 and cytochrome b genes were amplified to detect cat, dog, pig, monkey and rat species under complex matrices. Species-specificity was authenticated against 20 different species with the potential to be used in food. The targets were stable under extreme sterilisation (121°C at 45 psi for 2.5 h) which severely degrades DNA. The assay was optimised under the backgrounds of various commercial meat products and validated for the analysis of meatballs, burgers and frankfurters, which are popular fast food items across the globe. The assay was tested to detect 0.1% suspected meats under commercial backgrounds of marketed foods. Instead of simplex PCR which detects only one species at a time, such a multiplex platform can reduce cost by at least fivefolds by detecting five different species in a single assay platform.

  19. Safety assessment of boron by application of new uncertainty factors and their subdivision.

    Science.gov (United States)

    Hasegawa, Ryuichi; Hirata-Koizumi, Mutsuko; Dourson, Michael L; Parker, Ann; Ono, Atsushi; Hirose, Akihiko

    2013-02-01

    The available toxicity information for boron was reevaluated and four appropriate toxicity studies were selected in order to derive a tolerable daily intake (TDI) using newly proposed uncertainty factors (UFs) presented in Hasegawa et al. (2010). No observed adverse effect levels (NOAELs) of 17.5 and 8.8 mgB/kg/day for the critical effect of testicular toxicity were found in 2-year rat and dog feeding studies. Also, the 95% lower confidence limit of the benchmark doses for 5% reduction of fetal body weight (BMDL(05)) was calculated as 44.9 and 10.3 mgB/kg/day in mouse and rat developmental toxicity studies, respectively. Measured values available for differences in boron clearance between rats and humans and variability in the glomerular filtration rate (GFR) in pregnant women were used to derive chemical specific UFs. For the remaining uncertainty, newly proposed default UFs, which were derived from the latest applicable information with a probabilistic approach, and their subdivided factors for toxicokinetic and toxicodynamic variability were applied. Finally, overall UFs were calculated as 68 for rat testicular toxicity, 40 for dog testicular toxicity, 247 for mouse developmental toxicity and 78 for rat developmental toxicity. It is concluded that 0.13 mgB/kg/day is the most appropriate TDI for boron, based on rat developmental toxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Effect of α-naphthylisothiocyanate on blood clearance of 99mTc-phytate in dogs

    International Nuclear Information System (INIS)

    Shibata, Hiroshi; Kohno, Masahiro; Katoh, Hirotake

    1989-01-01

    The effect of α-naphthylisothiocyanate (ANIT) on blood clearance of 99m Tc-phytate ( 99m Tc-P) in dogs was examined, and blood clearance test of 99m Tc-P was compared with the cases of serum transaminase test or serum bilirubin test. Serum transaminase and bilirubin levels in dogs increased after ANIT administration, however, the degree of increase in these parameters was much lower than the cases in rats. The disappearance rate of 99m Tc-P from blood in dogs decreased with the increase in dose of ANIT and with the passage of time after the ANIT administration. Changes of the blood clearance of 99m Tc-P after ANIT treatment in dogs may be influenced by the disorder in the hepatocytes rather than in the bile ductule cells. The blood clearance test of 99m Tc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by ANIT equally to the serum transaminase test or the serum bilirubin test. (author)

  1. Molecular structure, bioinformatics analysis, expression and bioactivity of BAFF (TNF13B) in dog (Canis familiaris).

    Science.gov (United States)

    Shen, Yuefen; Wang, Shule; Ai, Hongxin; Min, Cui; Chen, Yuqing; Zhang, Shuangquan

    2011-07-15

    B cell activating factor (BAFF), belonging to the tumor necrosis factor (TNF) family, plays an important role in B cell survival, proliferation and differentiation. In the present study, we amplified the cDNA of dog (Canis familiaris) BAFF (designated doBAFF) from spleen by reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends (RACE) strategies. The open reading frame (ORF) of doBAFF covers 879 bp encoding 292 amino acids, with a 152-aa mature peptide. The soluble mature part of doBAFF (dosBAFF) shares 91.5%, 72.1%, 96.7%, 94.0% and 91.5% identity with the human, mouse, cattle, pig and rabbit counterparts, respectively. The predicted three-dimensional (3D) structural analysis of dosBAFF analyzed by "comparative protein modeling" revealed that it was very similar to its human counterpart. Real-time quantitative PCR analysis revealed that doBAFF was mainly expressed in spleen. Two fusion proteins SUMO-dosBAFF and GFP/dosBAFF were efficiently expressed in Escherichia coli BL21 (DE3) and purified using metal chelate affinity chromatography (Ni-NTA). Laser scanning confocal microscopy analysis showed that GFP/dosBAFF could bind to the mouse splenic B-cell. In vitro, SUMO-dosBAFF and GFP/dosBAFF were able to promote the survival/proliferation of dog lymphocytes or mouse splenic B cells with/without anti-IgM. Therefore, BAFF may be a potential immunologic factor for enhancing immunological efficacy in dog. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Identification of the porcine homologous of human disease causing trinucleotide repeat sequences

    DEFF Research Database (Denmark)

    Madsen, Lone Bruhn; Thomsen, Bo; Sølvsten, Christina Ane Elisabeth

    2007-01-01

    in this paper the identification of porcine noncoding and polyglutamine-encoding TNR regions and the comparison to the homologous TNRs from human, chimpanzee, dog, opossum, rat, and mouse. Several of the porcine TNR regions are highly polymorphic both within and between different breeds. The TNR regions...

  3. Dogs recognize dog and human emotions.

    Science.gov (United States)

    Albuquerque, Natalia; Guo, Kun; Wilkinson, Anna; Savalli, Carine; Otta, Emma; Mills, Daniel

    2016-01-01

    The perception of emotional expressions allows animals to evaluate the social intentions and motivations of each other. This usually takes place within species; however, in the case of domestic dogs, it might be advantageous to recognize the emotions of humans as well as other dogs. In this sense, the combination of visual and auditory cues to categorize others' emotions facilitates the information processing and indicates high-level cognitive representations. Using a cross-modal preferential looking paradigm, we presented dogs with either human or dog faces with different emotional valences (happy/playful versus angry/aggressive) paired with a single vocalization from the same individual with either a positive or negative valence or Brownian noise. Dogs looked significantly longer at the face whose expression was congruent to the valence of vocalization, for both conspecifics and heterospecifics, an ability previously known only in humans. These results demonstrate that dogs can extract and integrate bimodal sensory emotional information, and discriminate between positive and negative emotions from both humans and dogs. © 2016 The Author(s).

  4. Clinical Signs and Organ Pathology in Rats Exposed To Graded ...

    African Journals Online (AJOL)

    Olaleye

    pyrethroids-containing insecticides on farm and market produce and in human ... Key words: Pyrethroids, insecticides, rats, tissue pathology, public health hazard ... ingredients, differing in chemical structure or in ... meat shops, in poultry pens and on dogs and cats ... A total of 54 (27 male and 27 female) albino rats.

  5. Risk factors associated with Trypanosoma cruzi exposure in domestic dogs from a rural community in Panama.

    Science.gov (United States)

    Saldaña, Azael; Calzada, José E; Pineda, Vanessa; Perea, Milixa; Rigg, Chystrie; González, Kadir; Santamaria, Ana Maria; Gottdenker, Nicole L; Chaves, Luis F

    2015-11-01

    Chagas disease, caused by Trypanosoma cruzi infection, is a zoonosis of humans, wild and domestic mammals, including dogs. In Panama, the main T. cruzi vector is Rhodnius pallescens, a triatomine bug whose main natural habitat is the royal palm, Attalea butyracea. In this paper, we present results from three T. cruzi serological tests (immunochromatographic dipstick, indirect immunofluorescence and ELISA) performed in 51 dogs from 24 houses in Trinidad de Las Minas, western Panama. We found that nine dogs were seropositive (17.6% prevalence). Dogs were 1.6 times more likely to become T. cruzi seropositive with each year of age and 11.6 times if royal palms where present in the peridomiciliary area of the dog's household or its two nearest neighbours. Mouse-baited-adhesive traps were employed to evaluate 12 peridomestic royal palms. All palms were found infested with R. pallescens with an average of 25.50 triatomines captured per palm. Of 35 adult bugs analysed, 88.6% showed protozoa flagellates in their intestinal contents. In addition, dogs were five times more likely to be infected by the presence of an additional domestic animal species in the dog's peridomiciliary environment. Our results suggest that interventions focused on royal palms might reduce the exposure to T. cruzi infection.

  6. In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

    International Nuclear Information System (INIS)

    Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

    2006-01-01

    Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

  7. DogPulse

    DEFF Research Database (Denmark)

    Skovgaard, Christoffer; Thomsen, Josephine Raun; Verdezoto, Nervo

    2015-01-01

    This paper presents DogPulse, an ambient awareness system to support the coordination of dog walking among family members at home. DogPulse augments a dog collar and leash set to activate an ambient shape-changing lamp and visualize the last time the dog was taken for a walk. The lamp gradually...... changes its form and pulsates its lights in order to keep the family members aware of the dog walking activity. We report the iterative prototyping of DogPulse, its implementation and its preliminary evaluation. Based on our initial findings, we present the limitations and lessons learned as well...

  8. Prevalence of Giardia and Cryptosporidium species in dog park attending dogs compared to non-dog park attending dogs in one region of Colorado.

    Science.gov (United States)

    Wang, Andrea; Ruch-Gallie, Rebecca; Scorza, Valeria; Lin, Philip; Lappin, Michael R

    2012-03-23

    Dog parks are very popular in urban areas, but there are no current studies attempting to correlate visits to dog parks and risk of colonization by enteric parasites. The purpose of this study was to determine whether dog park visitation is associated with an increased prevalence of enteric parasites or an increase in prevalence of gastrointestinal signs in dogs in northern Colorado. Feces from dogs owned by veterinary students or Veterinary Teaching Hospital staff members were submitted with a completed survey form detailing dog park attendance rates, fecal character scores, and other clinical information. Feces were examined microscopically for parasites after sugar centrifugation, for Giardia spp. cysts and Cryptosporidium spp. oocysts by a commercially available immunofluorescence assay (FA) and the FA positive samples were genotyped after PCR amplification. The Giardia assemblages were determined using the glutamate dehydrogenase (GDH) β-giardin and triose phosphate isomerase (TPI) genes and the Cryptosporidium species were determined using the heat shock protein-70 gene. A total of 129 fecal samples were assayed; 66 were from dog park attending dogs and 63 were from non-dog park-attending dogs. The overall parasite prevalence rate was 7.0% (9 of 129 samples). Dog park attending dogs were more likely to be positive for Giardia or Cryptosporidium than non-dog park-attending dogs (p=0.0279), but there was no association of gastrointestinal signs with dog park attendance or with fecal flotation or FA results. The five Giardia isolates were assemblage C and/or D and the one Cryptosporidium isolate was Ctenocephalides canis. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Environmental Assessment: Black-Tailed Prairie Dog Management Cannon Air Force Base and Melrose Air Force Range, New Mexico

    Science.gov (United States)

    2005-12-01

    requirements are met by metabolizing grazed vegetation. Prairie dogs dig burrows to an average depth of 2-3 meters with some tunnels interconnecting with...the potential to impact non- target species such as mice, kangaroo rats, and some songbirds. Establishing control zones at CAFB and MAFR could not be...Gutierrezia sarothrae), and Russian thistle (Salsola iberica). Water requirements are met by metabolizing grazed vegetation. Prairie dogs dig burrows

  10. The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.

    Science.gov (United States)

    David, Dahlgren; Carl, Roos; Pernilla, Johansson; Christer, Tannergren; Anders, Lundqvist; Peter, Langguth; Markus, Sjöblom; Erik, Sjögren; Hans, Lennernäs

    2018-05-11

    Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients (CPEs), or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs/CPEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME/CPE effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME/CPE evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations. Copyright © 2018. Published by Elsevier B.V.

  11. An Efficient Method for Generation of Transgenic Rats Avoiding Embryo Manipulation

    Directory of Open Access Journals (Sweden)

    Bhola Shankar Pradhan

    2016-01-01

    Full Text Available Although rats are preferred over mice as an animal model, transgenic animals are generated predominantly using mouse embryos. There are limitations in the generation of transgenic rat by embryo manipulation. Unlike mouse embryos, most of the rat embryos do not survive after male pronuclear DNA injection which reduces the efficiency of generation of transgenic rat by this method. More importantly, this method requires hundreds of eggs collected by killing several females for insertion of transgene to generate transgenic rat. To this end, we developed a noninvasive and deathless technique for generation of transgenic rats by integrating transgene into the genome of the spermatogonial cells by testicular injection of DNA followed by electroporation. After standardization of this technique using EGFP as a transgene, a transgenic disease model displaying alpha thalassemia was successfully generated using rats. This efficient method will ease the generation of transgenic rats without killing the lives of rats while simultaneously reducing the number of rats used for generation of transgenic animal.

  12. Dog and owner demographic characteristics and dog personality trait associations.

    Science.gov (United States)

    Kubinyi, Eniko; Turcsán, Borbála; Miklósi, Adám

    2009-07-01

    The aim of this study was to analyze the relationships between four personality traits (calmness, trainability, dog sociability and boldness) of dogs (Canis familiaris) and dog and owner demographics on a large sample size with 14,004 individuals. German speaking dog owners could characterize their dog by filling out a form on the Internet. There were five demographic variables for dogs and nine for owners. Two statistical methods were used for investigating the associations between personality and demographic traits: the more traditional general linear methods and regression trees that are ideal for analyzing non-linear relationships in the structure of the data. The results showed that calmness is influenced primarily by the dog's age, the neutered status, the number of different types of professional training courses (e.g. obedience, agility) the dog had experienced and the age of acquisition. The least calm dogs were less than 2.5 years old, neutered and acquired after the first 12 weeks of age, while the calmest dogs were older than 6.9 years. Trainability was affected primarily by the training experiences, the dog's age, and the purpose of keeping the dog. The least trainable dogs had not received professional training at all and were older than 3 years. The most trainable dogs were those who participated in three or more types of professional training. Sociability toward conspecifics was mainly determined by the age, sex, training experience and time spent together. The least sociable dogs were older than 4.8 years and the owners spent less than 3h with the dog daily. The most sociable dogs were less than 1.5 years old. Males were less sociable toward their conspecifics than females. Boldness was affected by the sex and age of the dog and the age of acquisition. The least bold were females acquired after the age of 1 year or bred by the owner. The boldest dogs were males, acquired before the age of 12 weeks, and were younger than 2 years old. Other variables

  13. [Affective behavioural responses by dogs to tactile human-dog interactions].

    Science.gov (United States)

    Kuhne, Franziska; Hössler, Johanna C; Struwe, Rainer

    2012-01-01

    The communication of dogs is based on complex, subtle body postures and facial expressions. Some social interaction between dogs includes physical contact. Humans generally use both verbal and tactile signals to communicate with dogs. Hence, interaction between humans and dogs might lead to conflicts because the behavioural responses of dogs to human-dog interaction may be misinterpreted and wrongly assessed. The behavioural responses of dogs to tactile human-dog interactions and human gestures are the focus of this study. The participating dogs (n = 47) were privately owned pets.They were of varying breed and gender.The test consisted of nine randomised test sequences (e. g. petting the dog's head or chest). A test sequence was performed for a period of 30 seconds. The inter-trial interval was set at 60 seconds and the test-retest interval was set at 10 minutes. The frequency and duration of the dogs'behavioural responses were recorded using INTERACT. To examine the behavioural responses of the dogs, a two-way analysis of variance within the linear mixed models procedure of IBM SPSS Statistics 19 was conducted. A significant influence of the test-sequenc order on the dogs' behaviour could be analysed for appeasement gestures (F8,137 = 2.42; p = 0.018), redirected behaviour (F8,161 = 6.31; p = 0.012) and socio-positive behaviour (F8,148 = 6.28; p = 0.012). The behavioural responses of the dogs, which were considered as displacement activities (F8,109 = 2.5; p = 0.014) differed significantly among the test sequences. The response of the dogs, measured as gestures of appeasement, redirected behaviours, and displacement activities, was most obvious during petting around the head and near the paws.The results of this study conspicuously indicate that dogs respond to tactile human-dog interactions with gestures of appeasement and displacement activities. Redirected behaviours, socio-positive behaviours as well displacement activities are behavioural responses which dogs

  14. Effects of clofibric acid on mRNA expression profiles in primary cultures of rat, mouse and human hepatocytes.

    Science.gov (United States)

    Richert, Lysiane; Lamboley, Christelle; Viollon-Abadie, Catherine; Grass, Peter; Hartmann, Nicole; Laurent, Stephane; Heyd, Bruno; Mantion, Georges; Chibout, Salah-Dine; Staedtler, Frank

    2003-09-01

    The mRNA expression profile in control and clofibric acid (CLO)-treated mouse, rat, and human hepatocytes was analyzed using species-specific oligonucleotide DNA microarrays (Affymetrix). A statistical empirical Bayes procedure was applied in order to select the significantly differentially expressed genes. Treatment with the peroxisome proliferator CLO induced up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent but not of human origin. CLO treatment induced up-regulation of microsomal cytochrome P450 4a genes in rodent hepatocytes and in two of six human hepatocyte cultures. In addition, genes encoding phenobarbital-inducible cytochrome P450s were also up-regulated by CLO in rodent and human hepatocyte cultures. Up-regulation of phenobarbital-inducible UDP-glucuronosyl-transferase genes by CLO was observed in both rat and human but not in mouse hepatocytes. CLO treatment induced up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. However, while genes of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism were up-regulated by CLO in both rodent and human hepatocyte cultures, genes of the peroxisomal pathway of lipid metabolism were up-regulated in rodents only. An up-regulation of hepatocyte nuclear factor 1alpha (HNF1alpha) by CLO was observed only in human hepatocyte cultures, suggesting that this trans-activating factor may play a key role in the regulation of fatty acid metabolism in human liver as well as in the nonresponsiveness of human liver to CLO-induced regulation of cell proliferation and apoptosis.

  15. Effects of clofibric acid on mRNA expression profiles in primary cultures of rat, mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Richert, Lysiane; Lamboley, Christelle; Viollon-Abadie, Catherine; Grass, Peter; Hartmann, Nicole; Laurent, Stephane; Heyd, Bruno; Mantion, Georges; Chibout, Salah-Dine; Staedtler, Frank

    2003-01-01

    The mRNA expression profile in control and clofibric acid (CLO)-treated mouse, rat, and human hepatocytes was analyzed using species-specific oligonucleotide DNA microarrays (Affymetrix). A statistical empirical Bayes procedure was applied in order to select the significantly differentially expressed genes. Treatment with the peroxisome proliferator CLO induced up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent but not of human origin. CLO treatment induced up-regulation of microsomal cytochrome P450 4a genes in rodent hepatocytes and in two of six human hepatocyte cultures. In addition, genes encoding phenobarbital-inducible cytochrome P450s were also up-regulated by CLO in rodent and human hepatocyte cultures. Up-regulation of phenobarbital-inducible UDP-glucuronosyl-transferase genes by CLO was observed in both rat and human but not in mouse hepatocytes. CLO treatment induced up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. However, while genes of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism were up-regulated by CLO in both rodent and human hepatocyte cultures, genes of the peroxisomal pathway of lipid metabolism were up-regulated in rodents only. An up-regulation of hepatocyte nuclear factor 1α (HNF1α) by CLO was observed only in human hepatocyte cultures, suggesting that this trans-activating factor may play a key role in the regulation of fatty acid metabolism in human liver as well as in the nonresponsiveness of human liver to CLO-induced regulation of cell proliferation and apoptosis

  16. Job-Related Stress in Forensic Interviewers of Children with Use of Therapy Dogs Compared with Facility Dogs or No Dogs.

    Science.gov (United States)

    Walsh, Diane; Yamamoto, Mariko; Willits, Neil H; Hart, Lynette A

    2018-01-01

    Sexually abused children providing essential testimony regarding crimes in forensic interviews now sometimes are provided facility dogs or therapy dogs for comfort. Facility dogs are extensively trained to work with forensic interviewers; when using therapy dogs in interviews, volunteers are the dog handlers. Interviews can impact child welfare workers' mental health causing secondary traumatic stress (STS). To investigate this stress, first data were gathered on stress retrospectively for when interviewers initially started the job prior to working with a dog, and then currently, from forensic interviewers using a facility dog, a therapy or pet dog, or no dog. These retrospective and secondary traumatic stress scale (STSS) data compared job stress among interviewers of children using: a certified, workplace facility dog ( n  = 16), a volunteer's trained therapy dog or the interviewer's pet dog ( n  = 13/3), or no dog ( n  = 198). Retrospective scores of therapy dog and no dog interviewers' stress were highest for the first interviewing year 1 and then declined. Extremely or very stressful retrospective scores differed among the three groups in year 1 ( p  therapy dog group as compared with the facility dog group ( p  therapy dog users than no dog users ( p  dog users more consistently used dogs during interviews and conducted more interviews than therapy/pet dog users; both groups favored using dogs. Interviewers currently working with therapy dogs accompanied by their volunteers reported they had experienced heightened stress when they began their jobs; their high stress levels still persisted, indicating lower inherent coping skills and perhaps greater empathy among interviewers who later self-selected to work with therapy dogs. Results reveal extreme avoidant stress for interviewers witnessing children who are suffering and their differing coping approaches.

  17. A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors.

    Science.gov (United States)

    Blevitt, Jonathan M; Hack, Michael D; Herman, Krystal; Chang, Leon; Keith, John M; Mirzadegan, Tara; Rao, Navin L; Lebsack, Alec D; Milla, Marcos E

    2016-06-10

    5-Lipoxygenase activating protein (FLAP) plays a critical role in the metabolism of arachidonic acid to leukotriene A4, the precursor to the potent pro-inflammatory mediators leukotriene B4 and leukotriene C4 Studies with small molecule inhibitors of FLAP have led to the discovery of a drug binding pocket on the protein surface, and several pharmaceutical companies have developed compounds and performed clinical trials. Crystallographic studies and mutational analyses have contributed to a general understanding of compound binding modes. During our own efforts, we identified two unique chemical series. One series demonstrated strong inhibition of human FLAP but differential pharmacology across species and was completely inactive in assays with mouse or rat FLAP. The other series was active across rodent FLAP, as well as human and dog FLAP. Comparison of rodent and human FLAP amino acid sequences together with an analysis of a published crystal structure led to the identification of amino acid residue 24 in the floor of the putative binding pocket as a likely candidate for the observed speciation. On that basis, we tested compounds for binding to human G24A and mouse A24G FLAP mutant variants and compared the data to that generated for wild type human and mouse FLAP. These studies confirmed that a single amino acid mutation was sufficient to reverse the speciation observed in wild type FLAP. In addition, a PK/PD method was established in canines to enable preclinical profiling of mouse-inactive compounds. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

    Science.gov (United States)

    Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

    2008-04-01

    The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.

  19. Upper Airway Injury in Dogs Secondary to Trauma: 10 Dogs (2000-2011).

    Science.gov (United States)

    Basdani, Eleni; Papazoglou, Lysimachos G; Patsikas, Michail N; Kazakos, Georgios M; Adamama-Moraitou, Katerina K; Tsokataridis, Ioannis

    2016-01-01

    Ten dogs that presented with trauma-induced upper airway rupture or stenosis were reviewed. Tracheal rupture was seen in seven dogs, tracheal stenosis in one dog, and laryngeal rupture in two dogs. Clinical abnormalities included respiratory distress in five dogs, subcutaneous emphysema in eight, air leakage through the cervical wound in seven, stridor in three dogs, pneumomediastinum in four and pneumothorax in one dog. Reconstruction with simple interrupted sutures was performed in four dogs, tracheal resection and end-to-end anastomosis in five dogs, and one dog was euthanized intraoperatively. Complications were seen in three dogs including aspiration pneumonia in one and vocalization alterations in two dogs.

  20. Cloning and expression of canine CD25 for validation of an anti-human CD25 antibody to compare T regulatory lymphocytes in healthy dogs and dogs with osteosarcoma.

    Science.gov (United States)

    Rissetto, K C; Rindt, H; Selting, K A; Villamil, J A; Henry, C J; Reinero, C R

    2010-05-15

    T regulatory cells (Tregs) are a unique subset of T helper cells that serve to modify/inhibit effector cells of the immune system and thus are essential to prevent autoimmunity. Overzealous Treg activity may contribute to impaired immune responses to cancer. Tregs can be phenotypically identified by proteins expressed on the cell surface (CD4 and CD25) and inside the cell (forkhead box3 (FoxP3)), although in dogs, no anti-canine CD25 antibody exists. We hypothesized that a mouse anti-human CD25 antibody definitively recognizes the canine protein and can be used to identify Tregs in dogs. We describe cloning and transfection of the canine CD25 gene into human HeLa cells with subsequent expression of the canine protein on the cell surface detected using an anti-human CD25 antibody in a flow cytometric assay. Validation of this antibody was used to identify CD4+CD25+FoxP3+ Tregs in 39 healthy dogs and 16 dogs with osteosarcoma (OSA). Results were expressed in five different ways and showed significantly fewer %CD4+CD25+ T lymphocytes expressing FoxP3 in blood of older dogs (>/=7 years) compared with the other two age groups (<2 and 2-6 years) (p<0.001) and fewer %CD4+CD25+FoxP3+ Tregs in the tumor draining lymph nodes of OSA patients compared to the unrelated lymph node (p=0.049). However, there was no significant difference in % Tregs in the peripheral blood or lymph nodes between the control dogs and those with OSA. While the CD25 antibody can be successfully used in a flow cytometric assay to identify Tregs, this study does not support clinical utility of phenotypic recognition of Tregs in dogs with OSA. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Is your dog empathic? Developing a Dog Emotional Reactivity Survey.

    Science.gov (United States)

    Szánthó, Flóra; Miklósi, Ádám; Kubinyi, Enikő

    2017-01-01

    Dogs' seemingly empathic behaviour attracts general and scientific attention alike. Behaviour tests are usually not sufficiently realistic to evoke empathic-like behaviour; therefore we decided to ask owners about their experiences with their dogs in emotionally loaded situations. Owners from Hungary (N = 591) and from Germany (N = 2283) were asked to rate their level of agreement on a 1-5 Likert scale with statements about the reactivity of their dogs to their emotions and to other dogs' behaviour. We created two scales with satisfactory internal reliability: reactivity to the owner's emotion and reactivity to other dogs' behaviour. Based on an owner-dog personality matching theory, we hypothesised that the owner's empathy, as measured by the subscale on the cooperativeness character factor of the human personality, will correlate with their dog's emotional reactivity in emotionally loaded situations. In addition we also examined how anthropomorphism, contagious yawning, attitude toward the dog are related to emotional reactivity in dogs as perceived by the owner. In addition we examined how owners rate dog pictures. We found that the scale scores were largely independent from demographic and environmental variables like breed, sex, age, age at acquiring, keeping practices, training experiences and owner's age. However, anthropomorphic and emotional attitude of the owners probably biased the responses. In the German sample more empathic owners reported to have more emotionally reactive dog, as expected by the personality matching theory. More empathic owners reported to have fewer problems with their dogs and they rated a puppy picture as more cute in both countries. 62% of owners from Hungary and 36% of owner from Germany agreed with the statement "My dog is more important for me than any human being". In Germany, more empathic owners agreed less with this statement and indicated that their dogs have a tendency for contagious yawning. Owners whose attitudes

  2. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-07-18

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

  3. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years1–3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4,5. In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2,6. Here we identify a mechanism responsible for the naked mole-rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high molecular weight hyaluronan (HA), which is over five times larger than human or mouse HA. This high molecular weight HA accumulates abundantly in naked mole rat tissues due to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as the naked mole rat cells have a higher affinity to HA than the mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become susceptible to malignant transformation and readily form tumors in mice. We speculate that naked mole-rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. PMID:23783513

  4. Job-Related Stress in Forensic Interviewers of Children with Use of Therapy Dogs Compared with Facility Dogs or No Dogs

    Directory of Open Access Journals (Sweden)

    Diane Walsh

    2018-03-01

    Full Text Available Sexually abused children providing essential testimony regarding crimes in forensic interviews now sometimes are provided facility dogs or therapy dogs for comfort. Facility dogs are extensively trained to work with forensic interviewers; when using therapy dogs in interviews, volunteers are the dog handlers. Interviews can impact child welfare workers’ mental health causing secondary traumatic stress (STS. To investigate this stress, first data were gathered on stress retrospectively for when interviewers initially started the job prior to working with a dog, and then currently, from forensic interviewers using a facility dog, a therapy or pet dog, or no dog. These retrospective and secondary traumatic stress scale (STSS data compared job stress among interviewers of children using: a certified, workplace facility dog (n = 16, a volunteer’s trained therapy dog or the interviewer’s pet dog (n = 13/3, or no dog (n = 198. Retrospective scores of therapy dog and no dog interviewers’ stress were highest for the first interviewing year 1 and then declined. Extremely or very stressful retrospective scores differed among the three groups in year 1 (p < 0.038, and were significantly elevated for the therapy dog group as compared with the facility dog group (p < 0.035. All interviewing groups had elevated STSS scores; when compared with other healthcare groups that have been studied, sub-scores were especially high for Avoidance: a psychological coping mechanism to avoid dealing with a stressor. STSS scores differed among groups (p < 0.016, primarily due to Avoidance sub-scores (p < 0.009, reflecting higher Avoidance scores for therapy dog users than no dog users (p < 0.009. Facility dog users more consistently used dogs during interviews and conducted more interviews than therapy/pet dog users; both groups favored using dogs. Interviewers currently working with therapy dogs accompanied by their volunteers reported

  5. Job-Related Stress in Forensic Interviewers of Children with Use of Therapy Dogs Compared with Facility Dogs or No Dogs

    Science.gov (United States)

    Walsh, Diane; Yamamoto, Mariko; Willits, Neil H.; Hart, Lynette A.

    2018-01-01

    Sexually abused children providing essential testimony regarding crimes in forensic interviews now sometimes are provided facility dogs or therapy dogs for comfort. Facility dogs are extensively trained to work with forensic interviewers; when using therapy dogs in interviews, volunteers are the dog handlers. Interviews can impact child welfare workers’ mental health causing secondary traumatic stress (STS). To investigate this stress, first data were gathered on stress retrospectively for when interviewers initially started the job prior to working with a dog, and then currently, from forensic interviewers using a facility dog, a therapy or pet dog, or no dog. These retrospective and secondary traumatic stress scale (STSS) data compared job stress among interviewers of children using: a certified, workplace facility dog (n = 16), a volunteer’s trained therapy dog or the interviewer’s pet dog (n = 13/3), or no dog (n = 198). Retrospective scores of therapy dog and no dog interviewers’ stress were highest for the first interviewing year 1 and then declined. Extremely or very stressful retrospective scores differed among the three groups in year 1 (p pet dog users; both groups favored using dogs. Interviewers currently working with therapy dogs accompanied by their volunteers reported they had experienced heightened stress when they began their jobs; their high stress levels still persisted, indicating lower inherent coping skills and perhaps greater empathy among interviewers who later self-selected to work with therapy dogs. Results reveal extreme avoidant stress for interviewers witnessing children who are suffering and their differing coping approaches. PMID:29594160

  6. Unusual patch-matrix organization in the retrosplenial cortex of the reeler mouse and Shaking rat Kawasaki.

    Science.gov (United States)

    Ichinohe, Noritaka; Knight, Adrian; Ogawa, Masaharu; Ohshima, Toshio; Mikoshiba, Katsuhiko; Yoshihara, Yoshihiro; Terashima, Toshio; Rockland, Kathleen S

    2008-05-01

    The rat granular retrosplenial cortex (GRS) is a simplified cortex, with distinct stratification and, in the uppermost layers, distinct modularity. Thalamic and cortical inputs are segregated by layers and in layer 1 colocalize, respectively, with apical dendritic bundles originating from neurons in layers 2 or 5. To further investigate this organization, we turned to reelin-deficient reeler mouse and Shaking rat Kawasaki. We found that the disrupted lamination, evident in Nissl stains in these rodents, is in fact a patch-matrix mosaic of segregated afferents and dendrites. Patches consist of thalamocortical connections, visualized by vesicular glutamate transporter 2 (VGluT2) or AChE. The surrounding matrix consists of corticocortical terminations, visualized by VGluT1 or zinc. Dendrites concentrate in the matrix or patches, depending on whether they are OCAM positive (matrix) or negative (patches). In wild-type rodents and, presumably, mutants, OCAM(+) structures originate from layer 5 neurons. By double labeling for dendrites (filled by Lucifer yellow in fixed slice) and OCAM immunofluorescence, we ascertained 2 populations in reeler: dendritic branches either preferred (putative layer 5 neurons) or avoided (putative supragranular neurons) the OCAM(+) matrix. We conclude that input-target relationships are largely preserved in the mutant GRS and that dendrite-dendrite interactions involving OCAM influence the formation of the mosaic configuration.

  7. Toxicological study of DTPA as a drug, (4). Effect of intravenously injected DTPA on cardiovascular system in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi; Iida, Haruzo

    1988-09-01

    We have previously reported that the side effects on cardiovascular system such as the heart failure, increases of blood pressure and pulse accompanied with hypocalcemia occurred in rats when Zn-DTPA was injected intravenously, but those did not occur by Ca-DTPA. This is in the reverse that it is generally said that Zn-DTPA is more safe than Ca-DTPA. This study was carried out to examine whether the same side effects occurred in different animal species or not. Zn-DTPA or Ca-DTPA (30, 150, 300 and 600 ..mu..mol/kg) was injected intravenously to beagle dogs. The hypocalcemia was observed in the dogs by Zn-DTPA injection, but it was not by Ca-DTPA. After Zn-DTPA injection, the increase of blood pressure and pulse, and heart failure was observed in 3 out of 5 dogs at 300 ..mu..mol/kg dose, and in 3 out of 8 dogs at 600 ..mu..mol/kg dose. These changes were the same degrees as those in rats. In the present study, it is suggested that the side effects induced by Zn-DTPA intravenous injection occur independently of animal species and the data obtained from animal experiments can be available to estimate DTPA toxicity in humans.

  8. Dog and owner characteristics affecting the dog-owner relationship

    DEFF Research Database (Denmark)

    Meyer, Iben Helene Coakley; Forkman, Björn

    2014-01-01

    The nature of the relationship between companion dogs and their owners has important impact on the effect of life for both dog and owner. Identifying factors that affect the dogeowner relationship will assist the understanding of how the successful relationship is achieved and how the less...... successful relationship is mended, with potential benefits for the welfare of both species. In the present study, we investigated the effect of several dog and owner characteristics, including the personality of the dog, on the dogeowner relationship as measured by the Monash Dog Owner Relationship Scale...... (MDORS). Data were collected by inviting owners of dogs that had been tested on the Danish Dog Mentality Assessment (DMA) to answer an online questionnaire. We were able to match 421 owner answers with their dogs’ DMA test results. The questionnaire consisted of the 28 items of the MDORS, as well...

  9. Levels of α7 integrin and laminin-α2 are increased following prednisone treatment in the mdx mouse and GRMD dog models of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Ryan D. Wuebbles

    2013-09-01

    Duchenne muscular dystrophy (DMD is a fatal neuromuscular disease for which there is no cure and limited treatment options. Prednisone is currently the first line treatment option for DMD and studies have demonstrated that it improves muscle strength. Although prednisone has been used for the treatment of DMD for decades, the mechanism of action of this drug remains unclear. Recent studies have shown that the α7β1 integrin is a major modifier of disease progression in mouse models of DMD and is therefore a target for drug-based therapies. In this study we examined whether prednisone increased α7β1 integrin levels in mdx mouse and GRMD dog models and myogenic cells from humans with DMD. Our results show that prednisone promotes an increase in α7 integrin protein in cultured myogenic cells and in the muscle of mdx and GRMD animal models of DMD. The prednisone-mediated increase in α7 integrin was associated with increased laminin-α2 in prednisone-treated dystrophin-deficient muscle. Together, our results suggest that prednisone acts in part through increased merosin in the muscle basal lamina and through sarcolemmal stabilization of α7β1 integrin in dystrophin-deficient muscle. These results indicate that therapies that target an increase in muscle α7β1 integrin, its signaling pathways and/or laminin could be therapeutic in DMD.

  10. Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague–Dawley rats and C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Nault, Rance; Kim, Suntae; Zacharewski, Timothy R., E-mail: tzachare@msu.edu

    2013-03-01

    Although the structure and function of the AhR are conserved, emerging evidence suggests that downstream effects are species-specific. In this study, rat hepatic gene expression data from the DrugMatrix database (National Toxicology Program) were compared to mouse hepatic whole-genome gene expression data following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For the DrugMatrix study, male Sprague–Dawley rats were gavaged daily with 20 μg/kg TCDD for 1, 3 and 5 days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7 days after a single oral gavage of 30 μg/kg TCDD. A total of 649 rat and 1386 mouse genes (|fold change| ≥ 1.5, P1(t) ≥ 0.99) were differentially expressed following treatment. HomoloGene identified 11,708 orthologs represented across the rat Affymetrix 230 2.0 GeneChip (12,310 total orthologs), and the mouse 4 × 44K v.1 Agilent oligonucleotide array (17,578 total orthologs). Comparative analysis found 563 and 922 orthologs differentially expressed in response to TCDD in the rat and mouse, respectively, with 70 responses associated with immune function and lipid metabolism in common to both. Moreover, QRTPCR analysis of Ceacam1, showed divergent expression (induced in rat; repressed in mouse) functionally consistent with TCDD-elicited hepatic steatosis in the mouse but not the rat. Functional analysis identified orthologs involved in nucleotide binding and acetyltransferase activity in rat, while mouse-specific responses were associated with steroid, phospholipid, fatty acid, and carbohydrate metabolism. These results provide further evidence that TCDD elicits species-specific regulation of distinct gene networks, and outlines considerations for future comparisons of publicly available microarray datasets. - Highlights: ► We performed a whole-genome comparison of TCDD-regulated genes in mice and rats. ► Previous species comparisons were extended using data from the DrugMatrix database. ► Less than 15% of TCDD

  11. In vitro and in silico derived relative effect potencies of ah-receptor-mediated effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX cell lines.

    Science.gov (United States)

    Ghorbanzadeh, Mehdi; van Ede, Karin I; Larsson, Malin; van Duursen, Majorie B M; Poellinger, Lorenz; Lücke-Johansson, Sandra; Machala, Miroslav; Pěnčíková, Kateřina; Vondráček, Jan; van den Berg, Martin; Denison, Michael S; Ringsted, Tine; Andersson, Patrik L

    2014-07-21

    For a better understanding of species-specific relative effect potencies (REPs), responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated using chemical-activated luciferase gene expression assays (CALUX) derived from guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the rodent cell lines were partial agonists and less efficacious than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for each congener using concentrations at which 20% of the maximal TCDD response was reached (REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with their toxic equivalency factors assigned by the World Health Organization (WHO-TEF), while those for PCBs were in general lower than the WHO-TEF values. Moreover, the guinea pig cell line was the most sensitive as indicated by the 20% effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and mouse cells, respectively. A similar response pattern was observed using multivariate statistical analysis between the three CALUX assays and the WHO-TEFs. The mouse assay showed minor deviation due to higher relative induction potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8-hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was more than two times more potent in the mouse assay as compared with that of rat and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In order to provide REP20TCDD values for all WHO-TEF assigned compounds, quantitative structure-activity relationship (QSAR) models were developed. The QSAR models showed that specific electronic properties and molecular surface characteristics play important roles in the AhR-mediated response. In silico derived REP20TCDD values were generally consistent with the WHO

  12. Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse pep-3 (Dip-1) and human PEP-c.

    Science.gov (United States)

    Womack, J E; Cramer, D V

    1980-10-01

    Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).

  13. Primer registro del ratón de los volcanes (Neotomodon alstoni para el estado de Hidalgo, México First record of the volcano mouse (Neotomodon alstoni from the State of Hidalgo, Mexico

    Directory of Open Access Journals (Sweden)

    Alejandro García-Becerra

    2012-06-01

    Full Text Available El ratón de los volcanes (Neotomodon alstoni se registra por primera vez en el estado de Hidalgo, México. Los ejemplares se recolectaron en diciembre de 2010, en el municipio de Almoloya, aproximadamente a 32.8 km al norte de la localidad documentada más cercana al estado de Tlaxcala, por lo que este nuevo registro se convierte en el más norteño para la distribución conocida del ratón de los volcanes.The volcano mouse (Neotomodon alstoni is firstly recorded in the State of Hidalgo. Specimens were collected in December 2010, at the municipality of Almoloya, approximately 32.8 km to the north from the nearest locality in the state of Tlaxcala. Therefore, this is the northernmost record for the range of the Mexican volcano mouse.

  14. The Metabolism of Separase Inhibitor Sepin-1 in Human, Mouse, and Rat Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Feng Li

    2018-05-01

    Full Text Available Separase, a known oncogene, is widely overexpressed in numerous human tumors of breast, bone, brain, blood, and prostate. Separase is an emerging target for cancer therapy, and separase enzymatic inhibitors such as sepin-1 are currently being developed to treat separase-overexpressed tumors. Drug metabolism plays a critical role in the efficacy and safety of drug development, as well as possible drug–drug interactions. In this study, we investigated the in vitro metabolism of sepin-1 in human, mouse, and rat liver microsomes (RLM using metabolomic approaches. In human liver microsomes (HLM, we identified seven metabolites including one cysteine–sepin-1 adduct and one glutathione–sepin-1 adduct. All the sepin-1 metabolites in HLM were also found in both mouse and RLM. Using recombinant CYP450 isoenzymes, we demonstrated that multiple enzymes contributed to the metabolism of sepin-1, including CYP2D6 and CYP3A4 as the major metabolizing enzymes. Inhibitory effects of sepin-1 on seven major CYP450s were also evaluated using the corresponding substrates recommended by the US Food and Drug Administration. Our studies indicated that sepin-1 moderately inhibits CYP1A2, CYP2C19, and CYP3A4 with IC50 < 10 μM but weakly inhibits CYP2B6, CYP2C8/9, and CYP2D6 with IC50 > 10 μM. This information can be used to optimize the structures of sepin-1 for more suitable pharmacological properties and to predict the possible sepin-1 interactions with other chemotherapeutic drugs.

  15. Investigation into knowledge about dogs, dog ownership and the behavior of dog owners living in Germany

    OpenAIRE

    Brengelmann, Nathaly

    2010-01-01

    The aim of this work was to find out the level of knowledge of dog owners living in Germany; covering various aspects of dog handling, which personal and social circumstances have influence on this, and in which areas and which groups of people possible knowledge gaps exist. For this purpose, a multiple choice test was developed. This contained eight subject areas: “man-dog-relationship”, “puppy purchase and raising”, “learning behavior and training”, “dog behavior”, “keeping”, “dog and th...

  16. Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal mapping

    DEFF Research Database (Denmark)

    Ibaraki, K; Kozak, C A; Wewer, U M

    1995-01-01

    regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76......(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed...

  17. "She's a dog at the end of the day": Guide dog owners' perspectives on the behaviour of their guide dog.

    Directory of Open Access Journals (Sweden)

    Peter J Craigon

    Full Text Available A guide dog is a domestic dog (Canis familiaris that is specifically educated to provide mobility support to a blind or visually impaired owner. Current dog suitability assessments focus on behavioural traits, including: trainability, reactivity or attention to environmental stimuli, low aggressiveness, fearfulness and stress behaviour, energy levels, and attachment behaviour. The aim of this study was to find out which aspects of guide dog behaviour are of key importance to guide dog owners themselves. Sixty-three semi-structured interview surveys were carried out with guide dog owners. Topics included the behaviour of their guide dog both within and outside their working role, and also focused on examples of behaviour which might be considered outside a guide dog owner's typical expectations. Both positive and negative examples and situations were covered. This allowed for the discovery of new perspectives and emerging themes on living and working with a guide dog. Thematic analysis of the results reveals that a dog's safe behaviour in the face of traffic was the most important positive aspect of a guide dog's behaviour and pulling or high tension on the lead and /or harness was the most discussed negative aspect. Other aspects of guide dog behaviour were highlighted as particularly pleasing or disappointing by owners including attentiveness to the task, work, environment and owner; confidence in work and decision making (with confident dogs resulting in confident owners obedience and control; calmness and locating objectives. The results reveal important areas of behaviour that are not currently considered priorities in guide dog assessments; these key areas were consistency of behaviour, the dog's maturity and the dog's behaviour in relation to children. The survey revealed a large range in what owners considered problematic or pleasing behaviours and this highlights the heterogeneity in guide dog owners and the potential multifarious roles

  18. [Lens luxation in dogs: a retrospective study of 134 dogs (2000-2011)].

    Science.gov (United States)

    Betschart; Hässig; Spiess

    2014-03-01

    This retrospective study evaluated cases of lens luxation in dogs that were documented at the University of Zurich Veterinary Teaching Hospital between 2000 and 2011. A total 134 dogs were included in the study. This population of dogs with lens luxation represents 0.41 % of all dogs presented to the Zurich Veterinary Teaching Hospital (32'523) and 3.02 % of all dogs presented to the ophthalmology service during the same time period. The 134 dogs represented over 40 different breeds, including mixed breeds. 63 of the dogs were male, 71 were female. The 134 dogs were divided in primary lens luxation (86 of the 134 dogs, 64 %) and secondary lens luxation (48 dogs, 36 %). The most frequent causes for secondary lens luxation were glaucoma (58 %), cataract (19 %) and trauma (17 %). This study shows the predisposition for primary lens luxations in terrier breeds, Chinese Crested dogs, Pinscher and Spitz. In contrast, Siberian Huskies, Basset Hounds, Bearded Collies, Cairn Terriers, mixed breed dogs, Bolonka Zwetna, Boston Terriers, Borzoi, Doberman, Eurasian, Leonberg, Luzerner Niederlaufhund and Weimaraner suffered significantly more often from secondary lens luxation. There was no sex predilection for primary or secondary lens luxation. Dogs with primary lens luxation were on average 7.39 ± 3.02 years old, which is significantly younger than the dogs with secondary lens luxation (9.12 ± 3.38 years). Dogs with primary lens luxation showed a significantly higher rate of a bilateral development than those with secondary lens luxation (85.5 % of the dogs with primary lens luxation and only 14.5 % of the dogs with secondary lens luxation showed it in both their eyes).

  19. Radiographic liver size in Pekingese dogs versus other dog breeds.

    Science.gov (United States)

    Choi, Jihye; Keh, Seoyeon; Kim, Hyunwook; Kim, Junyoung; Yoon, Junghee

    2013-01-01

    Differential diagnoses for canine liver disease are commonly based on radiographic estimates of liver size, however little has been published on breed variations. Aims of this study were to describe normal radiographic liver size in Pekingese dogs and to compare normal measurements for this breed with other dog breeds and Pekingese dogs with liver disease. Liver measurements were compared for clinically normal Pekingese (n = 61), normal non-Pekingese brachycephalic (n = 45), normal nonbrachycephalic (n = 71), and Pekingese breed dogs with liver disease (n = 22). For each dog, body weight, liver length, T11 vertebral length, thoracic depth, and thoracic width were measured on right lateral and ventrodorsal abdominal radiographs. Liver volume was calculated using a formula and ratios of liver length/T11 vertebral length and liver volume/body weight ratio were determined. Normal Pekingese dogs had a significantly smaller liver volume/body weight ratio (16.73 ± 5.67, P dogs (19.54 ± 5.03) and normal nonbrachycephalic breed dogs (18.72 ± 6.52). The liver length/T11 vertebral length ratio in normal Pekingese (4.64 ± 0.65) was significantly smaller than normal non-Pekingese brachycephalic breed dogs (5.16 ± 0.74) and normal nonbrachycephalic breed dogs (5.40 ± 0.74). Ratios of liver volume/body weight and liver length/T11 vertebral length in normal Pekingese were significantly different from Pekingese with liver diseases (P dogs have a smaller normal radiographic liver size than other breeds. We recommend using 4.64× the length of the T11 vertebra as a radiographic criterion for normal liver length in Pekingese dogs. © 2012 Veterinary Radiology & Ultrasound.

  20. How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study.

    Directory of Open Access Journals (Sweden)

    Zdeněk Kříž

    Full Text Available Progressive cerebral deposition of amyloid beta occurs in Alzheimers disease and during the aging of certain mammals (human, monkey, dog, bear, cow, cat but not others (rat, mouse. It is possibly due to different amino acid sequences at positions 5, 10 and 13. To address this issue, we performed series of 100 ns long trajectories (each trajectory was run twice with different initial velocity distribution on amyloid beta (1-42 with the human and rat amino acid sequence in three different environments: water with only counter ions, water with NaCl at a concentration of 0.15 M as a model of intracellular Na(+ concentration at steady state, and water with NaCl at a concentration of 0.30 M as a model of intracellular Na(+ concentration under stimulated conditions. We analyzed secondary structure stability, internal hydrogen bonds, and residual fluctuation. It was observed that the change in ionic strength affects the stability of internal hydrogen bonds. Increasing the ionic strength increases atomic fluctuation in the hydrophobic core of the human amyloid, and decreases the atomic fluctuation in the case of rat amyloid. The secondary structure analyses show a stable α-helix part between residues 10 and 20. However, C-terminus of investigated amyloids is much more flexible showing no stable secondary structure elements. Increasing ionic strength of the solvent leads to decreasing stability of the secondary structural elements. The difference in conformational behavior of the three amino acids at position 5, 10 and 13 for human and rat amyloids significantly changes the conformational behavior of the whole peptide.

  1. In vitro gamma irradiation Medical Center of leukemic cells in mice, rats, and guinea pigs

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.; Ehrenreich, T.; Feldman, D.; Limbert, L.M.

    1980-01-01

    In vitro gamma irradiation of virus-induced (Gross) mouse leukemia cells at doses of 350 to 1600 rads (1 rad = 0.01 gray) had no effect on their ability to induce leukemia, usually within 2 weeks, after transplantation into syngeneic mice. However, when cells irradiated at doses of 2000-20,000 rads were transplanted, they induced leukemia after a latency period exceeding 2.5 months, similar to the results observed in mice inoculated with filtered mouse leukemia extracts. Similar results were also obtained after irradiation of leukemic cells derived from rats in which leukemia had been induced by rat-adapted mouse leukemia virus. Apparently, gamma irradiation at a dose of, or exceeding, 2000 rads, inhibits the ability of mouse and rat leukemic cells to induce leukemia after transplantation into syngeneic hosts; however, it does not inactivate the virus carried by such cells nor prevent it from inducing leukemia. [In previous experiments, doses of more than 4,500,000 rads were needed to inactivate the passage A (Gross) leukemia virus carried in either mouse or rat leukemic cells.] In vitro gamma irradiation of L2C guinea pig leukemic cells at doses of 750 to 2500 rads had no apparent effect on their ability to induce leukemia after transplantation into strain 2 guinea pigs. However, irradiation at doses of 3250 to 20,000 rads inactivated their ability to do so. The morphology of mouse, rat, and guinea pig leukemic cells and the virus particles present in such cells was not affected by irradiation at doses of 20,000 rads

  2. Dog-walking behaviours affect gastrointestinal parasitism in park-attending dogs.

    Science.gov (United States)

    Smith, Anya F; Semeniuk, Christina A D; Kutz, Susan J; Massolo, Alessandro

    2014-09-04

    In urban parks, dogs, wildlife and humans can be sympatric, introducing the potential for inter- and intra-specific transmission of pathogens among hosts. This study was conducted to determine the prevalence of zoonotic and non-zoonotic gastrointestinal parasites in dogs in Calgary city parks, and assess if dog-walking behaviour, park management, history of veterinary care, and dog demographics were associated with parasitism in dogs From June to September 2010, 645 questionnaires were administered to dog owners in nine city parks to determine behavioural and demographic factors, and corresponding feces from 355 dogs were collected. Dog feces were analyzed for helminth and some protozoan species using a modified sugar flotation technique and microscopic examination, a subsample was analyzed for Giardia spp. and Cryptosporidium spp. using a direct immunofluorescence assay. Descriptive and multivariate statistics were conducted to determine associations among behaviours, demographics, and parasite prevalence and infection intensities Parasite prevalence was 50.2%. Giardia spp. (24.7%), Cryptosporidium spp. (14.7%), and Cystoisospora spp. (16.8%) were the most prevalent parasites. Helminth prevalence was low (4.1%). Presence of Giardia spp. was more likely in intact and young dogs; and infection with any parasite and Giardia spp. intensity were both positively associated with dogs visiting multiple parks coupled with a high frequency of park use and off-leash activity, and with being intact and young. Cryptosporidium spp. intensity was associated with being intact and young, and having visited the veterinarian within the previous year Our results indicate a higher overall prevalence of protozoa in dogs than previously found in Calgary. The zoonotic potential of some parasites found in park-attending dogs may be of interest for public health. These results are relevant for informing park managers, the public health sector, and veterinarians.

  3. Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260

    International Nuclear Information System (INIS)

    Harrill, Alison H.; Eaddy, John S.; Rose, Kelly; Cullen, John M.; Ramanathan, Lakshmi; Wanaski, Stephen; Collins, Stephen; Ho, Yu; Watkins, Paul B.; LeCluyse, Edward L.

    2014-01-01

    NP260 was designed as a first-in-class selective antagonist of α4-subtype GABA A receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog > human > rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity. - Highlights: • NP260 caused ALT elevations in dogs without evidence of hepatocellular injury. • SDH, GLDH, and miRNA-122 elevations occurred, confirming hepatocellular necrosis. • NP260 toxicity is greater in dog and human hepatocytes than in rat hepatocytes. • Species sensitivity may explain why the rodent studies failed to indicate risk. • Diagnostic biomarkers and hepatocyte studies aid interpretation of hepatotoxicity

  4. Gastrointestinal absorption of plutonium in mice, rats, and dogs: application to establishing values of f1 for soluble plutonium

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Moretti, E.S.; Spaletto, M.I.

    1985-04-01

    The gastrointestinal (GI) absorption of plutonium was measured in mice, rats, and dogs under conditions relevant to setting drinking water standards. The fractional GI absorption of Pu(VI) in adult mice was 2 x 10 -4 (0.02%) in fed mice and 2 x 10 -3 (0.2%) in fasted mice. The GI absorption of plutonium was independent of plutonium oxidation state, administration medium, and plutonium concentration; absorption was dependent upon animal species, state of animal fasting, state of Pu(IV) hydrolysis, and age of the animal. Fractional GI absorption values ranged from 3 x 10 -5 (0.003%) for hydrolyzed Pu(IV) administered to fed adult mice to 7 x 10 -3 (0.7%) for Pu(VI) administered to fed neonatal rats. From analysis of our data, we suggested values of f 1 (the fraction transferred from gut to blood in humans) for use in establishment of oral limits of exposure to plutonium. For an acute exposure in the occupational setting, we proposed one value of f 1 for fed (2 x 10 -4 ) and one for fasted (2 x 10 -3 ) individuals. For the environmental setting, we developed two approaches to obtaining values of f 1 ; suggested values were 6 x 10 -4 and 4 x 10 -3 , respectively. Both approaches took into account effects of animal age and fasting. We discussed uncertainties in proposed values of f 1 and made recommendations for further research. 41 refs., 8 figs., 24 tabs

  5. Canine periodontitis: the dog as an important model for periodontal studies.

    Science.gov (United States)

    Albuquerque, Carlos; Morinha, Francisco; Requicha, João; Martins, Teresa; Dias, Isabel; Guedes-Pinto, Henrique; Bastos, Estela; Viegas, Carlos

    2012-03-01

    Periodontal disease (PD) refers to a group of inflammatory diseases caused by bacterial plaque in the periodontium and ranges from an early stage (gingivitis) to an advanced stage (periodontitis). It is a multifactorial disease that results from the interaction of the host defence mechanisms with the plaque microorganisms. Early detection, diagnosis and treatment are essential in the control of this disease. PD has an enormous impact on human and veterinary medicine due to its high prevalence. The most common animal PD models use dogs and non-human primates, although other animals (rats, mice, hamsters, rabbits, miniature pigs, ferrets, and sheep) have also been employed. Dog models have contributed significantly to the current understanding of periodontology. The most important clinical aspects of canine PD are considered in this review and the various animal models are examined with an emphasis on the role of the dog as the most useful approach for understanding human PD and in the development of new therapeutic and preventive measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Energy dispersive X-ray microanalysis of zinc and calcium in organelles of insulin-producing cells of the mouse, rat, and a fish

    Energy Technology Data Exchange (ETDEWEB)

    Falkmer, S; Odselius, R [Lund Univ. (Sweden); Blondel, B; Prentki, M; Wollheim, C B [Geneva Univ. (Switzerland)

    1985-01-01

    By means of energy dispersive X-ray microanalysis in the scanning-transmission electron microscope, spectra were obtained from quick-frozen, cryo-ultramicrotome-cut, freeze-dried sections of insulin cells from a fish and a mouse. It was shown that both zinc and calcium are present in significant quantities in native islet cell ..beta.. granules. In the ..beta.. granules of the rat RINm5F insuloma cells calcium, but not zinc, seemed to accumulate; the zinc contents in the secretion granules of these neoplastic ..beta.. cells were probably below the detection limit.

  7. Histological evaluation of the pulp in teeth from dogs with naturally occurring periodontal disease.

    Science.gov (United States)

    Nemec, Ana; Pavlica, Zlatko; Stiblar-Martincic, Draga; Petelin, Milan; Erzen, Damjan; Crossley, David

    2007-12-01

    The purpose of this investigation was to evaluate the pulp of dog teeth affected by advanced periodontal disease. Histological examination was done on demineralized teeth extracted during clinical treatment of mature, client owned small and medium-size breed dogs with either good periodontal health or with advanced naturally occurring periodontal disease. Routinely stained sections from 5 clinically normal teeth and 22 teeth with advanced periodontitis from dogs between 5 and 12-years of age were examined using light microscopy. The pulp cavities of most teeth were narrow with low cellularity and some fibrosis of the pulp. Findings specific to periodontally affected teeth included acute and chronic pulpitis, vascular congestion, and pulp necrosis. A glomus body was identified in the pulp of one tooth and areas of poorly mineralized cementum were seen in both normal and diseased teeth. Age related changes in dog teeth appear similar to those reported for man and the rat. In addition to age related changes, the pulp of dog teeth with advanced periodontal disease were frequently inflamed or necrotic. This may reflect the advanced periodontitis affecting these teeth or a mechanical effect related to excessive tooth mobility. Further study is required to determine the etiology and significance of these findings and to investigate pulp status in less severely diseased teeth.

  8. Dogs

    Science.gov (United States)

    ... Digital Press Kit Connect With Us New & Noteworthy Dogs Recommend on Facebook Tweet Share Compartir Overview Diseases ... healthy. Diseases The most common diseases associated with dogs that can cause human illness are: Campylobacteriosis ( Campylobacter ...

  9. Lasting engraftment of histoincompatible bone marrow cells in dogs

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-01-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed

  10. Lasting engraftment of histoincompatible bone marrow cells in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.C.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasng the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradiation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-h interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplotype-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  11. Lasting engraftment of histoincompatible bone marrow cells in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Vriesendorp, H.M.; Klapwijk, W.M.; van Kessel, A.M.; Zurcher, C.; van Bekkum, D.W.

    1981-05-01

    Conditioning protocols were tested for their efficacy in increasing the incidence of engraftment of histoincompatible dog bone marrow cells. Cyclophosphamide and total body irradation (TBI), Corynebacterium parvum and TBI, a 3- or 5-day delayed transfusion of bone marrow cells after TBI, or an increase in the number of donor bone marrow cells or lymphocytes appeared to be ineffective. These protocols were previously reported to promote recovery of splenic hemopoiesis in mice in short-term assays. The noted discrepancy between studies with mice and dogs invalidated allogeneic resistance as measured in the mouse spleen assay as a model for bone marrow allograft rejection. Intravenous treatment with silica particles or L-asparaginase did improve the engraftment rate after 7.5 Gy TBI. Low efficiency and significant extra toxicity restrict the applicability of these procedures. The most promising conditioning schedule found appeared to be two fractions of 6.0 Gy TBI separated by a 72-hr interval. Prolonged survival was noted after transplantation of bone marrow cells from a one-DLA haplo-type-mismatched donor. Possibilities for further improvement of this protocol are discussed.

  12. Do Dog Behavioral Characteristics Predict the Quality of the Relationship between Dogs and Their Owners?

    Science.gov (United States)

    Hoffman, Christy L; Chen, Pan; Serpell, James A; Jacobson, Kristen C

    This paper explores whether dog behavioral characteristics predict the quality of the relationship between dogs and their owners (i.e., owner attachment to dog), and whether relations between dog behavior and owner attachment are moderated by demographic characteristics. In this study, N = 92 children and N = 60 adults from 60 dog-owning families completed questionnaires about their attachment to their pet dog, their level of responsibility for that dog, and their general attitudes toward pets. They also rated their dogs on observable behavioral characteristics. Individuals who held positive attitudes about pets and who provided much of their dog's care reported stronger attachments to their dogs. The strength of owners' attachments to their dogs was associated with dog trainability and separation problems. Relationships between owner attachment and both dog excitability and attention-seeking behavior were further moderated by demographic characteristics: for Caucasians but not for non-Caucasians, dog excitability was negatively associated with owner attachment to dog; and for adults, dog attention-seeking behavior was positively associated with owner attachment, but children tended to be highly attached to their dogs, regardless of their dogs' attention-seeking behaviors. This study demonstrates that certain dog behavioral traits are indeed associated with the strength of owners' attachments to their dogs.

  13. Metabolism of cibenzoline in dogs

    International Nuclear Information System (INIS)

    Loh, A.C.; Williams, T.H.; Tilley, J.W.; Sasso, G.J.; Carbone, J.J.; Leinweber, F.J.; Cazes, M.

    1986-01-01

    The disposition of 14 C-cibenzoline in male dogs after oral administration of 13.8 mg/kg of cibenzoline base, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole, was investigated. Unchanged drug was the major excreted component in 0-24 h urine from 3 dogs, ranging from 32.2-56.6% of the dose. A phenolic metabolite was purified by TLC after Glusulase hydrolysis and identified by NMR and MS as p-hydroxycibenzoline in rearranged form, rac-4-[5-phenyl(2,3,6,7-tetrahydro-5H-pyrrolo-[1,2-a]imidazol-5-yl)] phenol. The 0-24 h urine contained 4-5% of the dose as this compound. The conditions leading to rearrangement of synthetic p-hydroxycibenzoline, trans-rac-4-[2-(4,5-dihydro-1H-imidazol-2-yl)-phenylcyclopropyl] phenol, were investigated. These studies suggested that unrearranged p-hydroxycibenzoline was excreted and that rearrangement occurred predominantly during the purification procedure. Unchanged cibenzoline, purified from urine, was analyzed by ORD/CD and found to display slight optical activity, corresponding to an optical purity of 15%. Shape of the spectra and sign (minus) were those of reference S(-) cibenzoline. p-Hydroxycibenzoline and its rearranged analog were only slightly active in inhibiting ventricular arrhythmia in rats induced by i.v. infusion of aconitine

  14. Digital three-dimensional reconstruction and ultrastructure of the mouse proximal tubule

    DEFF Research Database (Denmark)

    Zhai, X.Y.; Birn, H.; Jensen, K.B.

    2003-01-01

    . In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice......, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from...

  15. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting

    Science.gov (United States)

    Miller, Katherine A.; Touroo, Rachel; Spain, C. Victor; Jones, Kelly; Reid, Pamela; Lockwood, Randall

    2016-01-01

    Simple Summary Organizations responsible for placing dogs seized from dogfighting investigations often must determine if a particular dog should be euthanized because it is too dangerous or if it is safe to place the dog in an adoptive home. In this study, we examine whether the extent of scarring from dog fighting is a reliable predictor of aggression towards other dogs and therefore could be used to help make that decision. We found that dogs with 10 or more scars in the three body zones where dogfighting injuries tend to be concentrated were more likely, on average, to show aggression to other dogs. The relationship is imperfect, however. Many unscarred dogs were dog aggressive while some highly scarred dogs were not. Therefore, we recommend also assessing a dog’s behavior before making decisions about its disposition. Abstract When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs’ scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher’s Exact p < 0.001) than female dogs (Fisher’s Exact p = 0.05). Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to

  16. Improving guide dog team play with accessible dog toys

    NARCIS (Netherlands)

    Hauser, S.; Wakkary, R.L.; Neustaedter, C.

    2014-01-01

    People with vision impairment have been a longstanding well-recognized user group addressed in HCI. Despite the recent interest in studying sighted dog owners and their pets in HCI, there is a noticeable gap in the field with regards to research on visually impaired owners and their dogs (guide dog

  17. Genetic maps of polymorphic DNA loci on rat chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yan-Ping; Remmers, E.F.; Longman, R.E. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1996-09-01

    Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

  18. Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABA{sub A} receptor antagonist NP260

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Alison H., E-mail: ahharrill@uams.edu [College of Public Health, The University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Eaddy, John S. [The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Rose, Kelly [The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Cullen, John M. [College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607 (United States); Ramanathan, Lakshmi [QPS, Newark, DE 19711 (United States); Wanaski, Stephen; Collins, Stephen; Ho, Yu [NeuroTherapeutics Pharma, Inc., Chicago, IL 60631 (United States); Watkins, Paul B. [The Hamner-University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Schools of Pharmacy and Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); LeCluyse, Edward L. [The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2014-06-01

    NP260 was designed as a first-in-class selective antagonist of α4-subtype GABA{sub A} receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog > human > rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity. - Highlights: • NP260 caused ALT elevations in dogs without evidence of hepatocellular injury. • SDH, GLDH, and miRNA-122 elevations occurred, confirming hepatocellular necrosis. • NP260 toxicity is greater in dog and human hepatocytes than in rat hepatocytes. • Species sensitivity may explain why the rodent studies failed to indicate risk. • Diagnostic biomarkers and hepatocyte studies aid interpretation of hepatotoxicity.

  19. Incidence and impact of dog attacks on guide dogs in the UK: an update.

    Science.gov (United States)

    Moxon, R; Whiteside, H; England, G C W

    2016-04-09

    Data on dog attacks on Guide Dogs' stock were reviewed to investigate the characteristics of the attacks. An average of 11.2 attacks occurred each month. Nearly all of the attacks occurred in public areas, 68.4 per cent of victim dogs were qualified guide dogs and 55.5 per cent of victim dogs were working in harness when they were attacked. Guide Dogs' stock were injured in 43.2 per cent of attacks and veterinary costs for attacks were estimated at £34,514.30. Over 40 per cent of qualified guide dogs' working ability was affected and >20 per cent of qualified guide dogs required some time off from working after a dog attack. Twenty dogs were permanently withdrawn from the Guide Dogs' programme as a result of dog attacks, 13 of which were qualified and working with guide dog owners at the time of the withdrawal; this resulted in a financial cost of >£600,000 to the charity. More importantly perhaps, temporary and permanent withdrawals have a significant impact upon the mobility and independence of guide dog owners and in many cases significantly impacted their emotional well-being. British Veterinary Association.

  20. Comparison of P-wave dispersion in healthy dogs, dogs with chronic valvular disease and dogs with disturbances of supraventricular conduction

    Directory of Open Access Journals (Sweden)

    Nicpoń Józef

    2011-03-01

    Full Text Available Abstract Background P-wave dispersion (Pd is a new ECG index used in human cardiology and veterinary medicine. It is defined as the difference between the maximum and the minimum P-wave duration recorded from multiple different ECG leads. So far no studies were performed assessing the importance of P-wave dispersion in dogs. Methods The current study was aimed at determining proper value of Pd in healthy dogs (group I, dogs with chronic valvular disease (group II and dogs with disturbances of supraventricular conduction (group III. The tests were carried out in 53 healthy dogs, 23 dogs with chronic valvular disease and 12 dogs with disturbances of supraventricular conduction of various breeds, sexes and body weight from 1,5 to 80 kg, aged between 0,5 and 17 years, submitted to the ECG examination. ECG was acquired in dogs in a standing position with BTL SD-8 electrocardiographic device and analyzed once the recording was enlarged. P-wave duration was calculated in 9 ECG leads (I, II, III, aVR, aVL, aVF, V1, V2, V4 from 5 cardiac cycles. Results The proper P-wave dispersion in healthy dogs was determined at up to 24 ms. P-wave dispersion was statistically significant increased (p Conclusions The P-wave dispersion is a constant index in healthy dogs, that is why it can be used for evaluating P wave change in dogs with chronic valvular disease and in dogs with disturbances of supraventricular conduction.

  1. Do Dog Behavioral Characteristics Predict the Quality of the Relationship between Dogs and Their Owners?

    Science.gov (United States)

    Hoffman, Christy L.; Chen, Pan; Serpell, James A.; Jacobson, Kristen C.

    2014-01-01

    This paper explores whether dog behavioral characteristics predict the quality of the relationship between dogs and their owners (i.e., owner attachment to dog), and whether relations between dog behavior and owner attachment are moderated by demographic characteristics. In this study, N = 92 children and N = 60 adults from 60 dog-owning families completed questionnaires about their attachment to their pet dog, their level of responsibility for that dog, and their general attitudes toward pets. They also rated their dogs on observable behavioral characteristics. Individuals who held positive attitudes about pets and who provided much of their dog’s care reported stronger attachments to their dogs. The strength of owners’ attachments to their dogs was associated with dog trainability and separation problems. Relationships between owner attachment and both dog excitability and attention-seeking behavior were further moderated by demographic characteristics: for Caucasians but not for non-Caucasians, dog excitability was negatively associated with owner attachment to dog; and for adults, dog attention-seeking behavior was positively associated with owner attachment, but children tended to be highly attached to their dogs, regardless of their dogs’ attention-seeking behaviors. This study demonstrates that certain dog behavioral traits are indeed associated with the strength of owners’ attachments to their dogs. PMID:25685855

  2. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting

    Directory of Open Access Journals (Sweden)

    Katherine A. Miller

    2016-11-01

    Full Text Available When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs’ scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher’s Exact p < 0.001 than female dogs (Fisher’s Exact p = 0.05. Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to supplement scar counts when making disposition decisions about dogs seized in dogfighting investigations.

  3. Serial plasma glucose changes in dogs suffering from severe dog bite wounds.

    Science.gov (United States)

    Schoeman, J P; Kitshoff, A M; du Plessis, C J; Thompson, P N

    2011-03-01

    The objective of this study was to describe the changes in plasma glucose concentration in 20 severely injured dogs suffering from dog bite wounds over a period of 72 hours from the initiation of trauma. Historical, signalment, clinical and haematological factors were investigated for their possible effect on plasma glucose concentration. Haematology was repeated every 24 hours and plasma glucose concentrations were measured at 8-hourly intervals post-trauma. On admission, 1 dog was hypoglycaemic, 8 were normoglycaemic and 11 were hyperglycaemic. No dogs showed hypoglycaemia at any other stage during the study period. The median blood glucose concentrations at each of the 10 collection points, excluding the 56-hour and 64-hour collection points, were in the hyperglycaemic range (5.8- 6.2 mmol/l). Puppies and thin dogs had significantly higher median plasma glucose concentrations than adult and fat dogs respectively (P dogs survived the 72-hour study period. Overall 13 dogs (81.3 %) made a full recovery after treatment. Three of 4 dogs that presented in a collapsed state died, whereas all dogs admitted as merely depressed or alert survived (P = 0.004). The high incidence of hyperglycaemia can possibly be explained by the "diabetes of injury" phenomenon. However, hyperglycaemia in this group of dogs was marginal and potential benefits of insulin therapy are unlikely to outweigh the risk of adverse effects such as hypoglycaemia.

  4. A village dog is not a stray : human-dog interactions in coastal Mexico

    NARCIS (Netherlands)

    Ruiz Izaguirre, E.

    2013-01-01

    Dogs (Canis familiaris) are considered one of the most numerous carnivores worldwide. Although in the Global North dogs are popular companions, that live inside homes, about 80% of the dogs in the world are village dogs. Village dogs are typically free-roaming, scavenge refuse around

  5. Incidence and impact of dog attacks on guide dogs in the UK.

    Science.gov (United States)

    Brooks, A; Moxon, R; England, G C W

    2010-06-19

    In a retrospective survey, researchers identified 100 incidents of attacks on guide dogs by other dogs. These were reviewed in order to determine the number, severity and impact on the handler and dog, and the characteristics of the aggressors and victims. During the study period there were more than three attacks reported each month, with 61 per cent of the attacks being upon dogs that were in harness and working with an owner or trainer. The majority of the dogs that were attacked were male (62 per cent), and the breeds that were over-represented (relative to their prevalence in the general guide dog population) were the labrador and the golden retriever x flat-coated retriever crossbreed. Most of the attacks occurred in public places between 09.00 and 15.00 and the majority (61 per cent) of the attacking dogs were off the lead at the time of the attack. Thirty-eight per cent of the attacking dogs were of bull breeds, which were over-represented among attackers compared with the proportion of this breed type in the general dog population. Veterinary attention was sought after 41 per cent of the attacks, and in 19 per cent of instances there was injury to the handler or to a member of the public. The attacks were reported to have affected the working performance and behaviour of the victim dog in 45 per cent of the instances, and two dogs had to be subsequently withdrawn from working as guide dogs.

  6. Complex population structure in African village dogs and its implications for inferring dog domestication history.

    Science.gov (United States)

    Boyko, Adam R; Boyko, Ryan H; Boyko, Corin M; Parker, Heidi G; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A; Schoenebeck, Jeffrey; Todhunter, Rory J; Jones, Paul; Bustamante, Carlos D

    2009-08-18

    High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication.

  7. Generation and characterization of rat and mouse monoclonal antibodies specific for MeCP2 and their use in X-inactivation studies.

    Directory of Open Access Journals (Sweden)

    K Laurence Jost

    Full Text Available Methyl CpG binding protein 2 (MeCP2 binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates in heterochromatin. Even though it is expressed ubiquitously MeCP2 is particularly important during neuronal maturation. This is underscored by the fact that in Rett syndrome, a neurological disease, 80% of patients carry a mutation in the MECP2 gene. Since the MECP2 gene lies on the X chromosome and is subjected to X chromosome inactivation, affected patients are usually chimeric for wild type and mutant MeCP2. Here, we present the generation and characterization of the first rat monoclonal MeCP2 specific antibodies as well as mouse monoclonal antibodies and a rabbit polyclonal antibody. We demonstrate that our antibodies are suitable for immunoblotting, (chromatin immunoprecipitation and immunofluorescence of endogenous and ectopically expressed MeCP2. Epitope mapping revealed that most of the MeCP2 monoclonal antibodies recognize the C-terminal domain and one the N-terminal domain of MeCP2. Using slot blot analysis, we determined a high sensitivity of all antibodies, detecting amounts as low as 1 ng of MeCP2 protein. Moreover, the antibodies recognize MeCP2 from different species, including human, mouse, rat and pig. Lastly, we have validated their use by analyzing and quantifying X chromosome inactivation skewing using brain tissue of MeCP2 heterozygous null female mice. The new MeCP2 specific monoclonal antibodies described here perform well in a large variety of immunological applications making them a very valuable set of tools for studies of MeCP2 pathophysiology in situ and in vitro.

  8. Comparison of minipig, dog, monkey and human drug metabolism and disposition.

    Science.gov (United States)

    Dalgaard, Lars

    2015-01-01

    This article gives an overview of the drug metabolism and disposition (ADME) characteristics of the most common non-rodent species used in toxicity testing of drugs (minipigs, dogs, and monkeys) and compares these to human characteristics with regard to enzymes mediating the metabolism of drugs and the transport proteins which contribute to the absorption, distribution and excretion of drugs. Literature on ADME and regulatory guidelines of relevance in drug development of small molecules has been gathered. Non-human primates (monkeys) are the species that is closest to humans in terms of genetic homology. Dogs have an advantage due to the ready availability of comprehensive background data for toxicological safety assessment and dogs are easy to handle. Pigs have been used less than dogs and monkeys as a model in safety assessment of drug candidates. However, when a drug candidate is metabolised by aldehyde oxidase (AOX1), N-acetyltransferases (NAT1 and NAT2) or cytochrome (CYP2C9-like) enzymes which are not expressed in dogs, but are present in pigs, this species may be a better choice than dogs, provided that adequate exposure can be obtained in pigs. Conversely, pigs might not be the right choice if sulfation, involving 3-phospho-adenosyl-5-phosphosulphate sulphotransferase (PAPS) is an important pathway in the human metabolism of a drug candidate. In general, the species selection should be based on comparison between in vitro studies with human cell-based systems and animal-cell-based systems. Results from pharmacokinetic studies are also important for decision-making by establishing the obtainable exposure level in the species. Access to genetically humanized mouse models and highly sensitive analytical methods (accelerator mass spectrometry) makes it possible to improve the chance of finding all metabolites relevant for humans before clinical trials have been initiated and, if necessary, to include another animal species before long term toxicity studies are

  9. Urban dogs in rural areas: Human-mediated movement defines dog populations in southern Chile.

    Science.gov (United States)

    Villatoro, Federico J; Sepúlveda, Maximiliano A; Stowhas, Paulina; Silva-Rodríguez, Eduardo A

    2016-12-01

    Management strategies for dog populations and their diseases include reproductive control, euthanasia and vaccination, among others. However, the effectiveness of these strategies can be severely affected by human-mediated dog movement. If immigration is important, then the location of origin of dogs imported by humans will be fundamental to define the spatial scales over which population management and research should apply. In this context, the main objective of our study was to determine the spatial extent of dog demographic processes in rural areas and the proportion of dogs that could be labeled as immigrants at multiple spatial scales. To address our objective we conducted surveys in households located in a rural landscape in southern Chile. Interviews allowed us to obtain information on the demographic characteristics of dogs in these rural settings, human influence on dog mortality and births, the localities of origin of dogs living in rural areas, and the spatial extent of human-mediated dog movement. We found that most rural dogs (64.1%) were either urban dogs that had been brought to rural areas (40.0%), or adopted dogs that had been previously abandoned in rural roads (24.1%). Some dogs were brought from areas located as far as ∼700km away from the study area. Human-mediated movement of dogs, especially from urban areas, seems to play a fundamental role in the population dynamics of dogs in rural areas. Consequently, local scale efforts to manage dog populations or their diseases are unlikely to succeed if implemented in isolation, simply because dogs can be brought from surrounding urban areas or even distant locations. We suggest that efforts to manage or study dog populations and related diseases should be implemented using a multi-scale approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Nicolas O. Jørgensen

    2018-04-01

    Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

  11. Allegheny County Dog Licenses

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A list of dog license dates, dog breeds, and dog name by zip code. Currently this dataset does not include City of Pittsburgh dogs.

  12. High-performance liquid chromatography of rat and mouse islet polypeptides

    DEFF Research Database (Denmark)

    Linde, S; Hansen, B; Welinder, B S

    1990-01-01

    After preparative high-performance liquid chromatography of mouse islet culture medium, concentrated on disposable C18 cartridges (Sep-Pak), an unexpected insulin immunoreactive peak eluting earlier than mouse insulin I and II was detected. Molecular mass determination by mass spectrometry...... on the buffer, the organic modifier and the procedure. In particular the use of methanol-trifluoroacetic acid resulted in extensive oxidation. The oxidation could be minimized by adding 2 mM dithiothreitol to the buffer and by degassing and/or nitrogen-bubbling of the buffer. Minimal formation of Met...

  13. Serial plasma glucose changes in dogs suffering from severe dog bite wounds

    Directory of Open Access Journals (Sweden)

    J. P. Schoeman

    2011-04-01

    Full Text Available The objective of this study was to describe the changes in plasma glucose concentration in 20 severely injured dogs suffering from dog bite wounds over a period of 72 hours from the initiation of trauma. Historical, signalment, clinical and haematological factors were investigated for their possible effect on plasma glucose concentration. Haematology was repeated every 24 hours and plasma glucose concentrations were measured at 8-hourly intervals post-trauma. On admission, 1 dog was hypoglycaemic, 8 were normoglycaemic and 11 were hyperglycaemic. No dogs showed hypoglycaemia at any other stage during the study period. The median blood glucose concentrations at each of the 10 collection points, excluding the 56-hour and 64-hour collection points, were in the hyperglycaemic range (5.8– 6.2 mmol/ . Puppies and thin dogs had significantly higher median plasma glucose concentrations than adult and fat dogs respectively (P < 0.05 for both. Fifteen dogs survived the 72-hour study period. Overall 13 dogs (81.3 % made a full recovery after treatment. Three of 4 dogs that presented in a collapsed state died, whereas all dogs admitted as merely depressed or alert survived (P = 0.004. The high incidence of hyperglycaemia can possibly be explained by the ’diabetes of injury“ phenomenon. However, hyperglycaemia in this group of dogs was marginal and potential benefits of insulin therapy are unlikely to outweigh the risk of adverse effects such as hypoglycaemia.

  14. Assisting Handlers Following Attacks on Dog Guides: Implications for Dog Guide Teams

    Science.gov (United States)

    Godley, Cheryl A.; Gillard, Marc A.

    2011-01-01

    Attacks by dogs on dog guides are traumatic for dog guide teams. One variable that affects a team's recovery is how handlers cope with emotional responses to the attack. This article presents a three-stage model for assisting handlers that is useful for handlers and dog guide instructors.

  15. Interspecific and geographic variation in the diets of sympatric carnivores: dingoes/wild dogs and red foxes in south-eastern Australia.

    Directory of Open Access Journals (Sweden)

    Naomi E Davis

    Full Text Available Dingoes/wild dogs (Canis dingo/familiaris and red foxes (Vulpes vulpes are widespread carnivores in southern Australia and are controlled to reduce predation on domestic livestock and native fauna. We used the occurrence of food items in 5875 dingo/wild dog scats and 11,569 fox scats to evaluate interspecific and geographic differences in the diets of these species within nine regions of Victoria, south-eastern Australia. The nine regions encompass a wide variety of ecosystems. Diet overlap between dingoes/wild dogs and foxes varied among regions, from low to near complete overlap. The diet of foxes was broader than dingoes/wild dogs in all but three regions, with the former usually containing more insects, reptiles and plant material. By contrast, dingoes/wild dogs more regularly consumed larger mammals, supporting the hypothesis that niche partitioning occurs on the basis of mammalian prey size. The key mammalian food items for dingoes/wild dogs across all regions were black wallaby (Wallabia bicolor, brushtail possum species (Trichosurus spp., common wombat (Vombatus ursinus, sambar deer (Rusa unicolor, cattle (Bos taurus and European rabbit (Oryctolagus cuniculus. The key mammalian food items for foxes across all regions were European rabbit, sheep (Ovis aries and house mouse (Mus musculus. Foxes consumed 6.1 times the number of individuals of threatened Critical Weight Range native mammal species than did dingoes/wild dogs. The occurrence of intraguild predation was asymmetrical; dingoes/wild dogs consumed greater biomass of the smaller fox. The substantial geographic variation in diet indicates that dingoes/wild dogs and foxes alter their diet in accordance with changing food availability. We provide checklists of taxa recorded in the diets of dingoes/wild dogs and foxes as a resource for managers and researchers wishing to understand the potential impacts of policy and management decisions on dingoes/wild dogs, foxes and the food

  16. Cloning of rat thymic stromal lymphopoietin receptor (TSLPR) and characterization of genomic structure of murine Tslpr gene

    DEFF Research Database (Denmark)

    Blagoev, Blagoy; Nielsen, Mogens M; Angrist, Misha

    2002-01-01

    , a cytokine involved in B- and T-cell function. We have cloned the TSLP receptor from rat and find that the WSXWX motif commonly found in extracellular domains of cytokine receptors is conserved as a W(T/S)XV(T/A) motif among TSLP receptors from mouse, rat and human. As in the mouse, TSLP receptor is widely...

  17. Tracing the origin of 'blue Weimaraner' dogs by molecular genetics.

    Science.gov (United States)

    Gerding, W M; Schreiber, S; Dekomien, G; Epplen, J T

    2011-04-01

    Weimaraner dogs are defined by light brown coat colour termed grey including several shadings ranging from silver and deer to mouse grey. In contrast, the so-called blue Weimaraners (BW) with lightened black-pigmented coat have been proposed to represent spontaneous revertants in the Weimaraner breed. In order to investigate the genetic determinants of the characteristic grey coat colour versus those of BW, known variation in coat colour genes including TYRP1 and MLPH were analysed in a number of grey and blue dogs. Variations at the B locus cause grey coat colour in Weimaraners via two non-functional TYRP1 copies (bb) including the b(s), b(d) and b(c) alleles. In all BW, at least one functional TYRP1 allele (Bb or BB genotype) was identified. Defined microsatellite alleles in TYRP1 intron 4 are linked to this functional B allele in BW. These alleles were also detected in various other dog breeds, but not in grey Weimaraners. The combination of a dominant trait for blue versus grey together with a specific TYRP1 haplotype in BW suggests that blue coat colour is not the result of spontaneous (back-) mutation in grey Weimaraners. This inference is even emphasized by the presence of a unique Y-chomosomal haplotype in a male offspring of the supposed ancestor of the BW population which - according to pedigree information - carries a copy of the original Y chromosome. Thus, molecular genetic analyses of coat colours combined with Y-chromosomal haplotypes allow tracing the origin of atypical dogs in respective canine populations. © 2010 Blackwell Verlag GmbH.

  18. Distribution of sulfhydryl boranes in mice and rats

    International Nuclear Information System (INIS)

    Slatkin, D.N.; Micca, P.L.; Laster, B.H.; Fairchild, R.G.

    1986-01-01

    The distribution of boron in mice bearing transplanted Harding-Passey melanomas after rapid and slow administration of monomer were studied. Thin layer chromatographic analysis of the corresponding infusion solution revealed a slow-moving principal band that was later shown to correspond to Na 4 B 24 H 22 S 2 , the dimer of Na 2 B 12 H 11 SH. It was found that while monomer and chemically synthesized dimer yielded similar boron concentrations when they were given rapidly intraperitoneally to mice, the dimer yielded higher boron concentrations in mouse melanoma and higher melanoma-blood boron concentration when each was infused slowly intraperitoneally for 8 to 9 days. Studies have been started on the uptake of dimer into an intracerebrally implanted rat glioma. Boron levels in the rat glioma and in the mouse melanoma from slow intraperitoneal infusion of proportionately comparable amounts of dimer, are similar. However, after these slow infusions boron levels in rat blood are about as high as boron levels in rat brain tumor. 6 refs., 1 fig., 4 tabs

  19. Dog ownership, dog walking, and leisure-time walking among Taiwanese metropolitan and nonmetropolitan older adults.

    Science.gov (United States)

    Liao, Yung; Huang, Pin-Hsuan; Chen, Yi-Ling; Hsueh, Ming-Chun; Chang, Shao-Hsi

    2018-04-04

    This study examined the prevalence of dog ownership and dog walking and its association with leisure-time walking among metropolitan and nonmetropolitan older adults. A telephone-based cross-sectional survey targeting Taiwanese older adults was conducted in November 2016. Data related to dog ownership, time spent dog walking (categorized as non-dog owner, non-dog walkers, and dog walkers), and sociodemographic variables were obtained from 1074 older adults. Adjusted binary logistic regression was then performed. In this sample, 12% of Taiwanese older adults owned a dog and 31% of them walked their dogs for an average of 232.13 min over 5.9 days/week (standard deviation = 2.03). Older adults living in nonmetropolitan areas were more likely to own a dog (14.7% vs. 9.1%) but less likely to walk their dog (25.9% vs. 39.6%) than were those living in metropolitan areas. Compared with non-dog owners, only older adults living in nonmetropolitan areas who were dog walkers achieved 150 min of leisure-time walking (odds ratio: 3.03, 95% confidence interval: 1.05-8.77), after adjustment for potential confounders. Older Taiwanese adults living in nonmetropolitan areas who owned and walked their dogs were more likely to achieve health-enhancing levels of leisure-time walking. Tailored physical activity interventions for promoting dog walking should be developed for older adults who are dog owners living in nonmetropolitan areas and who do not engage in dog walking.

  20. Antibody response to an anti-rabies vaccine in a dog population under field conditions in Bolivia.

    Science.gov (United States)

    Suzuki, K; González, E T; Ascarrunz, G; Loza, A; Pérez, M; Ruiz, G; Rojas, L; Mancilla, K; Pereira, J A C; Guzman, J A; Pecoraro, M R

    2008-10-01

    Rabies remains an important public health issue in Bolivia, South America. Public concern and fears are most focussed on dogs as the source of rabies. The objective of the present study was to assess immunity of an inactivated suckling mouse brain vaccine against canine rabies used for the official vaccination campaigns under field conditions in an endemic area of rabies in Bolivia. A total of 236 vaccinated and 44 unvaccinated dogs in Santa Cruz de la Sierra, selected using stratified random sampling, were investigated in order to obtain owned dog characteristics and antibody titres against rabies in April 2007. The proportion of vaccinated dogs with an antibody titre exceeded the protection threshold value of 0.5 EU/ml was 58% [95% confidence intervals (CI): 52-65], indicating that vaccination is likely to elicit an antibody response (odds ratio 6.3, 95% CI: 1.2-11.5). The range of geometric mean of antibody titre for vaccinated dogs (0.89 EU/ml; 95% CI: 0.75-1.04) was considered to meet the minimal acceptable level indicating an adequate immune response to the vaccine. However, the titre level was not satisfactory in comparison with the results from other field investigations with inactivated tissue culture vaccines. It is recommended for public health authorities to (1) consider modernizing their vaccine manufacturing method because the level of immunity induced by the current vaccine is comparably low, (2) conduct frequent vaccination campaigns to maintain high levels of vaccination coverage, and (3) actively manage the domestic dog population in the study area, which is largely responsible for rabies maintenance.

  1. 'Who's a good boy?!' Dogs prefer naturalistic dog-directed speech.

    Science.gov (United States)

    Benjamin, Alex; Slocombe, Katie

    2018-05-01

    Infant-directed speech (IDS) is a special speech register thought to aid language acquisition and improve affiliation in human infants. Although IDS shares some of its properties with dog-directed speech (DDS), it is unclear whether the production of DDS is functional, or simply an overgeneralisation of IDS within Western cultures. One recent study found that, while puppies attended more to a script read with DDS compared with adult-directed speech (ADS), adult dogs displayed no preference. In contrast, using naturalistic speech and a more ecologically valid set-up, we found that adult dogs attended to and showed more affiliative behaviour towards a speaker of DDS than of ADS. To explore whether this preference for DDS was modulated by the dog-specific words typically used in DDS, the acoustic features (prosody) of DDS or a combination of the two, we conducted a second experiment. Here the stimuli from experiment 1 were produced with reversed prosody, meaning the prosody and content of ADS and DDS were mismatched. The results revealed no significant effect of speech type, or content, suggesting that it is maybe the combination of the acoustic properties and the dog-related content of DDS that modulates the preference shown for naturalistic DDS. Overall, the results of this study suggest that naturalistic DDS, comprising of both dog-directed prosody and dog-relevant content words, improves dogs' attention and may strengthen the affiliative bond between humans and their pets.

  2. Immunohistochemical analysis of the distribution of desmoglein 1 and 2 in the skin of dogs and cats.

    Science.gov (United States)

    Miragliotta, Vincenzo; Coli, Alessandra; Ricciardi, Maria P; Podestà, Adriano; Abramo, Francesca

    2005-11-01

    To compare the distribution of desmoglein (Dsg) 1 and 2 in skin specimens obtained from dogs and cats to provide information about the possible role of the density of Dsg 1 and 2 in the localization of lesions attributable to pemphigus foliaceus in these 2 species. Skin biopsy specimens obtained from 4 dogs and 4 cats. Biopsy specimens were collected from the muzzle, bridge of the nose, ear, dorsum, abdomen, area adjacent to the teats, and footpads of each animal. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded skin samples by use of a biotinylated mouse monoclonal anti-Dsg 1 and 2 antibody raised against bovine muzzle. Color development was performed by use of the streptavidin-biotin-peroxidase method with a chromogenic substrate. Immunohistochemical staining yielded a positive reaction in skin samples obtained from all anatomic sites. The intensity and distribution of staining were related to the number of layers of the stratum spinosum. No differences were detected between samples obtained from dogs and cats. No differences in intensity of Dsg 1 and 2 antigen were observed in the stratum spinosum between skin samples obtained from dogs and cats. Analysis of this result suggests that factors other than the distribution of Dsg may be responsible for the differences in localization of primary clinical lesions in dogs and cats with pemphigus foliaceus.

  3. Be your dog

    OpenAIRE

    Bartram, Angela

    2016-01-01

    Be Your Dog is about establishing relationships beyond the hierarchies of pet and owner. This saw participants and their dogs attend workshops over two consecutive weekends to learn how to establish empathy, equality and connection. This included learning strategies for dog and human to ‘be’ equals with each other. A concluding public event was staged at KARST (Plymouth) following the workshops on 6 November 2016 where all participants, human and dog, performed as collaborators. This proj...

  4. (New imaging systems in nuclear medicine)

    Energy Technology Data Exchange (ETDEWEB)

    1990-01-01

    Further progress has been made on improving the uniformity and stability of PCR-I, the single ring analog coded tomograph. This camera has been employed in a wide range of animal studies described below. Data from PCR-I have been used in various image processing procedures. These include motion pictures of dog heart, comparison of PET and MRI image in dog heart and rat brain and quantitation of tumor metabolism in the nude mouse using blood data from heart images. A SUN workstation with TAAC board has been used to produce gated three-dimensional images of the dog heart. The ANALYZE program from the Mayo Clinic has also been mounted on a SUN workstation for comparison of images and image processing. 15 refs., 6 figs.

  5. [New imaging systems in nuclear medicine

    International Nuclear Information System (INIS)

    1990-01-01

    Further progress has been made on improving the uniformity and stability of PCR-I, the single ring analog coded tomograph. This camera has been employed in a wide range of animal studies described below. Data from PCR-I have been used in various image processing procedures. These include motion pictures of dog heart, comparison of PET and MRI image in dog heart and rat brain and quantitation of tumor metabolism in the nude mouse using blood data from heart images. A SUN workstation with TAAC board has been used to produce gated three-dimensional images of the dog heart. The ANALYZE program from the Mayo Clinic has also been mounted on a SUN workstation for comparison of images and image processing. 15 refs., 6 figs

  6. Cat and Dog Bites

    Science.gov (United States)

    ... Wellness Staying Healthy Pets and Animals Cat and Dog Bites Cat and Dog Bites Share Print Cat and dog bites are common injuries. A family pet or ... bites. Path to safety If a cat or dog bites you, you should: Wash the wound gently ...

  7. “She’s a dog at the end of the day”: Guide dog owners’ perspectives on the behaviour of their guide dog

    Science.gov (United States)

    Craigon, Peter J.; Hobson- West, Pru; England, Gary C. W.; Whelan, Chantelle; Lethbridge, Emma; Asher, Lucy

    2017-01-01

    A guide dog is a domestic dog (Canis familiaris) that is specifically educated to provide mobility support to a blind or visually impaired owner. Current dog suitability assessments focus on behavioural traits, including: trainability, reactivity or attention to environmental stimuli, low aggressiveness, fearfulness and stress behaviour, energy levels, and attachment behaviour. The aim of this study was to find out which aspects of guide dog behaviour are of key importance to guide dog owners themselves. Sixty-three semi-structured interview surveys were carried out with guide dog owners. Topics included the behaviour of their guide dog both within and outside their working role, and also focused on examples of behaviour which might be considered outside a guide dog owner’s typical expectations. Both positive and negative examples and situations were covered. This allowed for the discovery of new perspectives and emerging themes on living and working with a guide dog. Thematic analysis of the results reveals that a dog’s safe behaviour in the face of traffic was the most important positive aspect of a guide dog’s behaviour and pulling or high tension on the lead and /or harness was the most discussed negative aspect. Other aspects of guide dog behaviour were highlighted as particularly pleasing or disappointing by owners including attentiveness to the task, work, environment and owner; confidence in work and decision making (with confident dogs resulting in confident owners) obedience and control; calmness and locating objectives. The results reveal important areas of behaviour that are not currently considered priorities in guide dog assessments; these key areas were consistency of behaviour, the dog’s maturity and the dog’s behaviour in relation to children. The survey revealed a large range in what owners considered problematic or pleasing behaviours and this highlights the heterogeneity in guide dog owners and the potential multifarious roles of the

  8. Borders and Comparative Cytoarchitecture of the Perirhinal and Postrhinal Cortices in an F1 Hybrid Mouse

    Science.gov (United States)

    Beaudin, Stephane A.; Singh, Teghpal; Agster, Kara L.

    2013-01-01

    We examined the cytoarchitectonic and chemoarchitectonic organization of the cortical regions associated with the posterior rhinal fissure in the mouse brain, within the framework of what is known about these regions in the rat. Primary observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1 hybrid was chosen because of the many advantages afforded in the study of the molecular and cellular bases of learning and memory. Comparisons with the parent strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was processed for visualization of Nissl material, myelin, acetyl cholinesterase, parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm’s method was particularly useful in the assignment of borders and in the comparative analyses because the patterns of staining were similar across species and strains. As in the rat, the areas examined were parcellated into 2 regions, the perirhinal and the postrhinal cortices. The perirhinal cortex was divided into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd) and ventral (PORv) subregions. In addition to identifying the borders of the perirhinal cortex, we were able to identify a region in the mouse brain that shares signature features with the rat postrhinal cortex. PMID:22368084

  9. Pet dogs and child physical activity: the role of child-dog attachment.

    Science.gov (United States)

    Gadomski, A M; Scribani, M B; Krupa, N; Jenkins, P

    2017-10-01

    Dog ownership has been associated with increased physical activity in children which in turn may mitigate childhood obesity. To measure the association between child-dog attachment and child physical activity and screen time. Cross-sectional study including 370 children (ages 4-10) who had pet dogs in the home. Parents completed the DartScreen, a web-based screener, before a well-child visit. Screener domains included child body mass index (BMI), physical activity, screen time and dog-related questions. The Companion Animal Bonding Scale (CABS) was used to measure child attachment to the dog. Clinic nurses weighed and measured the children. Associations between CABS, BMI z-score, screen time and physical activity were estimated. CABS was strongly associated with time spent being active with the dog (F = 22.81, p dog is associated with increased child physical activity. © 2016 World Obesity Federation.

  10. Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

    DEFF Research Database (Denmark)

    Overgaard, Agnete; Tena-Sempere, Manuel; Franceschini, Isabelle

    2013-01-01

    cells, only after axonal transport inhibition. Interestingly, the density of kisspeptin innervation in the anterior periventricular area was higher in female compared to male in both species. Species differences in the ARC were evident, with the mouse ARC containing dense fibers, while the rat ARC......-immunoreactivity in the mouse compared to the rat, independently of brain region and gender. In the female mouse AVPV high numbers of kisspeptin-immunoreactive neurons were present, while in the rat, the female AVPV displays a similar number of kisspeptin-immunoreactive neurons compared to the level of Kiss1 mRNA expressing...... contains clearly discernable cells. In addition, we show a marked sex difference in the ARC, with higher kisspeptin levels in females. These findings show that the translation of Kiss1 mRNA and/or the degradation/transportation/release of kisspeptins are different in mice and rats....

  11. Dog-directed speech: why do we use it and do dogs pay attention to it?

    Science.gov (United States)

    Ben-Aderet, Tobey; Gallego-Abenza, Mario; Reby, David; Mathevon, Nicolas

    2017-01-11

    Pet-directed speech is strikingly similar to infant-directed speech, a peculiar speaking pattern with higher pitch and slower tempo known to engage infants' attention and promote language learning. Here, we report the first investigation of potential factors modulating the use of dog-directed speech, as well as its immediate impact on dogs' behaviour. We recorded adult participants speaking in front of pictures of puppies, adult and old dogs, and analysed the quality of their speech. We then performed playback experiments to assess dogs' reaction to dog-directed speech compared with normal speech. We found that human speakers used dog-directed speech with dogs of all ages and that the acoustic structure of dog-directed speech was mostly independent of dog age, except for sound pitch which was relatively higher when communicating with puppies. Playback demonstrated that, in the absence of other non-auditory cues, puppies were highly reactive to dog-directed speech, and that the pitch was a key factor modulating their behaviour, suggesting that this specific speech register has a functional value in young dogs. Conversely, older dogs did not react differentially to dog-directed speech compared with normal speech. The fact that speakers continue to use dog-directed with older dogs therefore suggests that this speech pattern may mainly be a spontaneous attempt to facilitate interactions with non-verbal listeners. © 2017 The Author(s).

  12. Dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

    Science.gov (United States)

    Kujala, Miiamaaria V; Kujala, Jan; Carlson, Synnöve; Hari, Riitta

    2012-01-01

    We read conspecifics' social cues effortlessly, but little is known about our abilities to understand social gestures of other species. To investigate the neural underpinnings of such skills, we used functional magnetic resonance imaging to study the brain activity of experts and non-experts of dog behavior while they observed humans or dogs either interacting with, or facing away from a conspecific. The posterior superior temporal sulcus (pSTS) of both subject groups dissociated humans facing toward each other from humans facing away, and in dog experts, a distinction also occurred for dogs facing toward vs. away in a bilateral area extending from the pSTS to the inferior temporo-occipital cortex: the dissociation of dog behavior was significantly stronger in expert than control group. Furthermore, the control group had stronger pSTS responses to humans than dogs facing toward a conspecific, whereas in dog experts, the responses were of similar magnitude. These findings suggest that dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

  13. Dog Ownership, Dog Walking, and Children's and Parents' Physical Activity

    Science.gov (United States)

    Salmon, Jo; Timperio, Anna; Chu, Binh; Veitch, Jenny

    2010-01-01

    This study aimed to determine cross-sectional associations of dog ownership, dog walking, and physical activity (PA) among children and their parents. Objective measures of PA were obtained for children ages 5-6 and 10-12 years from 19 primary schools across Melbourne, Australia. Parents self-reported their PA, dog ownership, and frequency of dog…

  14. Home - DOG

    Science.gov (United States)

    Newsroom Services Information Why Alaska? DOG 101 Director & Deputy Bios Division Experts Applications — Give Feedback Thanks for giving feedback! The captcha entered is not valid. Send Close DOG DOA DNR

  15. Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Ramensky Vasily E

    2007-01-01

    Full Text Available Abstract Background The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci ( Description To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at http://bioinfo.embl.it/SnpApplet/. For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. Conclusion We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously

  16. Dogs catch human yawns

    OpenAIRE

    Joly-Mascheroni, Ramiro M; Senju, Atsushi; Shepherd, Alex J

    2008-01-01

    This study is the first to demonstrate that human yawns are possibly contagious to domestic dogs (Canis familiaris). Twenty-nine dogs observed a human yawning or making control mouth movements. Twenty-one dogs yawned when they observed a human yawning, but control mouth movements did not elicit yawning from any of them. The presence of contagious yawning in dogs suggests that this phenomenon is not specific to primate species and may indicate that dogs possess the capacity for a rudimentary f...

  17. Do Dogs Provide Information Helpfully?

    Directory of Open Access Journals (Sweden)

    Patrizia Piotti

    Full Text Available Dogs are particularly skilful during communicative interactions with humans. Dogs' abilities to use human communicative cues in cooperative contexts outcompete those of other species, and might be the result of selection pressures during domestication. Dogs also produce signals to direct the attention of humans towards outside entities, a behaviour often referred to as showing behaviour. This showing behaviour in dogs is thought to be something dogs use intentionally and referentially. However, there is currently no evidence that dogs communicate helpfully, i.e. to inform an ignorant human about a target that is of interest to the human but not to the dog. Communicating with a helpful motive is particularly interesting because it might suggest that dogs understand the human's goals and need for information. In study 1, we assessed whether dogs would abandon an object that they find interesting in favour of an object useful for their human partner, a random novel distractor, or an empty container. Results showed that it was mainly self-interest that was driving the dogs' behaviour. The dogs mainly directed their behaviour towards the object they had an interest in, but dogs were more persistent when showing the object relevant to the human, suggesting that to some extent they took the humans interest into account. Another possibility is that dogs' behaviour was driven by an egocentric motivation to interact with novel targets and that the dogs' neophila might have masked their helpful tendencies. Therefore, in study 2 the dogs had initial access to both objects, and were expected to indicate only one (relevant or distractor. The human partner interacted with the dog using vocal communication in half of the trials, and remaining silent in the other half. Dogs from both experimental groups, i.e. indicating the relevant object or indicating the distractor, established joint attention with the human. However, the human's vocal communication and the

  18. Do Dogs Provide Information Helpfully?

    Science.gov (United States)

    Piotti, Patrizia; Kaminski, Juliane

    2016-01-01

    Dogs are particularly skilful during communicative interactions with humans. Dogs' abilities to use human communicative cues in cooperative contexts outcompete those of other species, and might be the result of selection pressures during domestication. Dogs also produce signals to direct the attention of humans towards outside entities, a behaviour often referred to as showing behaviour. This showing behaviour in dogs is thought to be something dogs use intentionally and referentially. However, there is currently no evidence that dogs communicate helpfully, i.e. to inform an ignorant human about a target that is of interest to the human but not to the dog. Communicating with a helpful motive is particularly interesting because it might suggest that dogs understand the human's goals and need for information. In study 1, we assessed whether dogs would abandon an object that they find interesting in favour of an object useful for their human partner, a random novel distractor, or an empty container. Results showed that it was mainly self-interest that was driving the dogs' behaviour. The dogs mainly directed their behaviour towards the object they had an interest in, but dogs were more persistent when showing the object relevant to the human, suggesting that to some extent they took the humans interest into account. Another possibility is that dogs' behaviour was driven by an egocentric motivation to interact with novel targets and that the dogs' neophila might have masked their helpful tendencies. Therefore, in study 2 the dogs had initial access to both objects, and were expected to indicate only one (relevant or distractor). The human partner interacted with the dog using vocal communication in half of the trials, and remaining silent in the other half. Dogs from both experimental groups, i.e. indicating the relevant object or indicating the distractor, established joint attention with the human. However, the human's vocal communication and the presence of the

  19. Nasal carriage of Staphylococcus schleiferi from healthy dogs and dogs with otitis, pyoderma or both.

    Science.gov (United States)

    May, Elizabeth R; Kinyon, Joann M; Noxon, James O

    2012-12-07

    In veterinary medicine, Staphylococcus schleiferi was previously assumed to be an inhabitant of carnivore skin, however, more recently, it has been repeatedly documented in the literature as both an inhabitant and as a pathogen. In order to determine the frequency of nasal carriage, and the methicillin susceptibility pattern of S. schleiferi from healthy dogs as well as dogs with otitis and/or pyoderma, a prospective study including 24 dogs with healthy ears and skin, 27 dogs with healthy ears and pyoderma, 15 dogs with otitis without pyoderma and 20 dogs with both otitis and pyoderma was performed. Specimens were obtained and cultured and isolates were identified as S. schleiferi based on growth and biochemical characteristics. S. schleiferi was isolated from the nares of 1 healthy dog, 3 dogs with recurrent pyoderma, 2 dogs with recurrent otitis, and 1 dog with both recurrent otitis and pyoderma. One of the S. schleiferi isolates was methicillin resistant. Nasal carriage of S. schleiferi does occur in healthy dogs as well as dogs with otitis and pyoderma. Methicillin resistant and sensitive S. schleiferi can be found in the nares of dogs with diseased ears and skin. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Analysis of purified gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and tandem mass spectrometry.

    Science.gov (United States)

    Fairburn, B; Muthana, M; Hopkinson, K; Slack, L K; Mirza, S; Georgiou, A S; Espigares, E; Wong, C; Pockley, A G

    2006-09-01

    The stress protein gp96 exhibits a number of immunological activities, the majority of studies into which have used gp96 purified from a variety of tissues. On the basis of 1-D gel electrophoresis, the purity of these preparations has been reported to range between 70% and 99%. This study analyzed gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry (MS-MS). The procedure for purifying gp96 was reproducible, as similar protein profiles were observed in replicate gels of gp96 preparations. The purity of the preparations was typically around 70%, with minor co-purified proteins of varying molecular weights and mobilities being present. Dominant bands at 95-100 kDa in preparations from Wistar rats and C57BL/6 mice were identified as gp96 by ECL Western blotting. Multiple bands having similar, yet distinct molecular weights and differing pI mobility on ECL Western blots were confirmed as being gp96 in preparations from Wistar rats using MS-MS. The most striking feature of the 2-D gel analysis was the presence of additional dominant bands at 55 kDa in preparations from Wistar rats, and at 75-90 kDa in preparations from C57BL/6 mice. These were identified as gp96 by ECL Western blotting and, in the case of preparations from Wistar rats, by MS-MS. Although the lower molecular weight, gp96-related molecules might be partially degraded gp96, their reproducible presence, definition and characteristics suggest that they are alternative, species-specific isoforms of the molecule. A 55 kDa protein which exhibited a lower pI value than gp96 was present in all preparations and this was identified as calreticulin, another putative immunoregulatory molecule. This study confirms the reproducibility of the gp96 purification protocol and reveals the presence of multiple gp96 isoforms, some of which likely result from post-translational modifications such as differential glycosylation and

  1. Demography and dog-human relationships of the dog population in Zimbabwean communal lands.

    Science.gov (United States)

    Butler, J R; Bingham, J

    2000-10-14

    Dogs are Zimbabwe's primary vector for rabies, and the majority live in communal lands (traditional agropastoralist rural areas). In 1994, a household questionnaire survey was conducted to provide baseline data on the demography and dog-human relationships of the dogs in the communal lands. The survey showed that all the dogs were owned, and there was no evidence of a feral population. They were unrestricted and semi-dependent on people. The numbers of dogs per capita varied little in each communal land, resulting in higher dog densities in communal lands with higher human densities, and indicating that people were not intolerant of dogs at higher densities. The population turnover was rapid: the life expectancy of the dogs was 1.1 years, the mean age 2.0 years, and 71.8 per cent died in their first year. The population was heavily skewed towards juveniles, with 40.8 per cent aged less than 12 months. Despite the high juvenile mortality, the population was growing by 6.52 per cent per annum. It was estimated that in 1994 there were 1.36 million dogs in communal lands.

  2. Cloning of cDNAs that encode human mast cell carboxypeptidase A, and comparison of the protein with mouse mast cell carboxypeptidase A and rat pancreatic carboxypeptidases

    International Nuclear Information System (INIS)

    Reynolds, D.S.; Gurley, D.S.; Stevens, R.L.; Austen, K.F.; Serafin, W.E.; Sugarbaker, D.J.

    1989-01-01

    Human skin and lung mast cells and rodent peritoneal cells contain a carboxypeptidase in their secretory granules. The authors have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA. The 5' end of the human MC-CPA transcript was defined by direct mRNA sequencing and by isolation and partial sequencing of the human MC-CPA gene. Human MC-CPA is predicted to be translated as a 417 amino acid preproenzyme which includes a 15 amino acid signal peptide and a 94-amino acid activation peptide. The mature human MC-CPA enzyme has a predicted size of 36.1 kDa, a net positive charge of 16 at neutral pH, and 86% amino acid sequence identity with mouse MC-CPA. DNA blot analyses showed that human MC-CPA mRNA is transcribed from a single locus in the human genome. Comparison of the human MC-CPA with mouse MC-CPA and with three rat pancreatic carboxypeptidases shows that these enzymes are encoded by distinct but homologous genes

  3. 9 CFR 355.16 - Control of flies, rats, mice, etc.

    Science.gov (United States)

    2010-01-01

    ... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF...

  4. Histological changes of the adult albino rats entorhinal cortex under ...

    African Journals Online (AJOL)

    Ibrahim K. Ragab

    2016-06-03

    Jun 3, 2016 ... Treated group received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks. All ani- ... withdrawal reactions include restlessness, agitation, anxiety, ... (in particular, selective serotonin reuptake inhibitors and ... out in rats, dogs and rabbits. ... tionally accepted principles for laboratory animal use and care.

  5. Care of dogs and attitudes of dog owners in Port-au-Prince, the Republic of Haiti.

    Science.gov (United States)

    Fielding, William J; Gall, Melanie; Green, Dick; Eller, Warren S

    2012-01-01

    This article reports the first known study on dogs in Port-au-Prince. Interviews with 1,290 residents provided information on 1,804 dogs. More than 57.7% of homes kept dogs. Not all the dogs received vaccinations for rabies (41.6%), even though 28.2% of households had had a household member bitten by a dog. Although the "owned" dog population had decreased as a result of the earthquake in January 2010, the number of roaming dogs appeared to have been uninfluenced by the disaster. Given that 64.8% of dogs probably had access to the street and only 6.0% of the females were spayed, to humanely contain the dog population will require both confinement and neutering. Although roaming dogs were considered a nuisance by 63.3% of respondents, 42.6% of households fed dogs they did not own.

  6. Dietary hyperthyroidism in dogs.

    Science.gov (United States)

    Köhler, B; Stengel, C; Neiger, R

    2012-03-01

    Evaluation of dogs with elevated plasma thyroxine concentration fed raw food before and after changing the diet. Between 2006 and 2011 all dogs presented with an elevated plasma thyroxine concentration and a dietary history of feeding raw food were included. Thyroxine (reference interval: 19·3 to 51·5 nmol/L) and in many cases also thyroid-stimulating hormone concentrations (reference interval: weight loss, aggressiveness, tachycardia, panting and restlessness while six dogs had no clinical signs. After changing the diet eight dogs were examined: thyroxine concentration normalised in all dogs and clinical signs resolved. Dietary hyperthyroidism can be seen in dogs on a raw meat diet or fed fresh or dried gullets. Increased plasma thyroxine concentration in a dog, either with or without signs of hyperthyroidism, should prompt the veterinarian to obtain a thorough dietary history. © 2012 British Small Animal Veterinary Association.

  7. Simultaneous quantitation of polygalaxanthone III and four ginsenosides by ultra-fast liquid chromatography with tandem mass spectrometry in rat and beagle dog plasma after oral administration of Kai-Xin-San: application to a comparative pharmacokinetic study.

    Science.gov (United States)

    Lv, Chunxiao; Li, Qing; Zhang, Xiaowen; He, Bosai; Xu, Huarong; Yin, Yidi; Liu, Ran; Liu, Jingjing; Chen, Xiaohui; Bi, Kaishun

    2014-05-01

    A fast, selective, and quantitative ultra-fast liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation of polygalaxanthone III, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1 in the plasma of rat and beagle dog after oral administration of Kai-Xin-San. After addition of the internal standard, salidroside, the plasma samples were extracted by liquid-liquid extraction and separated on a Venusil MP C18 column with methanol/0.01% acetic acid water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in a switching ionization mode. The method was examined, and found to be precise and accurate with the linearity range of the compounds. The intra- and interday precision and accuracy of the analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard were all >75.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat and beagle dog plasma. The results indicated that no significant differences were observed in pharmacokinetic parameters of ginsenoside Rg1, while the others had significant differences, which may due to the different mechanisms of absorption and metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Splenitis in 33 Dogs.

    Science.gov (United States)

    Ferri, F; Zini, E; Auriemma, E; Castagnaro, M; Coppola, L M; Peano, A; Martella, V; Decaro, N; Kuhnert, P; Ferro, S

    2017-01-01

    Splenitis is uncommonly reported in dogs. Herein, the authors describe its prevalence, clinical findings and outcomes, histologic patterns, and causes. Splenic samples of dogs diagnosed with splenitis between 2005 and 2013 were collected and stained with hematoxylin and eosin, Gram, green-Gram, Giemsa, periodic acid-Schiff, and Ziehl-Neelsen. Samples were processed for polymerase chain reaction (PCR) to detect bacteria, fungi, and protozoa ( Leishmania infantum, Hepatozoon canis). Thirty-three of 660 splenic samples (5%) had splenitis. Clinical findings and outcomes were available in 19 dogs (58%); 49% had weakness, 33% had fever, and 84% survived. The most frequent inflammatory patterns included purulent splenitis (27%), pyogranulomatous splenitis (24%), and neutrophilic perisplenitis (15%). One dog had a putative diagnosis of primary splenitis; in 8 dogs, microorganisms were identified histologically or by PCR in the spleen without obvious comorbidities. Twenty-four dogs (73%) had concurrent diseases; a permissive role in the development of splenitis was suspected in 21 of these cases. Histologic examination identified the cause of splenitis in 10 dogs. Bacteria were identified by PCR in 23 cases, but the bacteria were confirmed histologically in only 6 of these. Leishmania was detected with PCR in 6 dogs. Leishmania was identified in 1 dog and H. canis in another histologically, but both were PCR negative. Fungi were identified in 8 spleens by PCR and in 1 by histology. This study suggests that splenitis is uncommon in dogs and is frequently associated with systemic diseases. Prognosis is favorable in most cases. Identification of bacteria, fungi, and protozoa in the spleens of affected dogs with PCR should be interpreted cautiously, because the findings are not confirmed histologically in many cases.

  9. Toxicity studies on the radioprotective agent WR-2721 in CDF1 mice and beagle dogs

    International Nuclear Information System (INIS)

    Palmer, T.E.; Glaza, S.M.; Dickie, B.C.; Weltman, R.H.; Greenspun, K.S.

    1985-01-01

    WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is used extensively to protect normal cells during the irradiation of neoplastic cells. Dose levels for human radiotherapy are based on results obtained from laboratory animal lethality and toxicity studies. WR-2721 was administered intravenously to CDF1 mice and beagle dogs. Single dose lethality studies in mice showed the average 1/10 of the lethal dose, the median lethal dose and 9/10 the lethal dose to be 508 (1523 mg/m2), 589 (1766 mg/m2), and 682 mg/kg (2047 mg/m2), respectively. The lethal dose for female mice was lower than that for males. The 1/10 lethal dose in mice was slightly toxic to dogs; 1/10 of that dose was nontoxic. The lethal dose for dogs (6000 mg/m2) was higher than that for mice (2000 mg/m2). Clinical signs of toxicosis in the single-dose mouse toxicity study were evident in the 1st week following treatment and declined during the recovery period; signs of toxicosis were transient in dogs. Acute drug-induced pathologic changes included elevated BUN and SGOT levels, lymphoid necrosis, and renal tubular degeneration in mice. These changes were evident in the 1st week following treatment, but had dissipated by study termination. Generalized vascular changes (congestion, hemorrhage, and edema) and renal tubular degeneration occurred in treated dogs that had died or were killed moribund 7 days postinjection. These findings indicate sex-dependent and interspecies variation in the toxicity of WR-2721 with acute, but reversible, pathologic changes

  10. Owned and Unowned Dog Population Estimation, Dog Management and Dog Bites to Inform Rabies Prevention and Response on Lombok Island, Indonesia

    Science.gov (United States)

    Mustiana, Ana; Toribio, Jenny-Ann; Abdurrahman, Muktasam; Suadnya, I. Wayan; Hernandez-Jover, Marta; Putra, Anak Agung Gde; Ward, Michael P.

    2015-01-01

    Although Indonesia has been rabies-infected since at least the 1880s, some islands remain rabies-free, such as Lombok. However, due to its adjacency to rabies-infected islands such as Bali and Flores, there is considerable risk of a rabies incursion. As part of a rabies risk assessment project, surveys were conducted to estimate the size of the dog population and to describe dog management practices of households belonging to different ethnic groups. A photographic-recapture method was employed and the number of unowned dogs was estimated. A total of 400 dog owning households were interviewed, 300 at an urban site and 100 at a rural site. The majority of the interviewed households belonged to the Balinese ethnic group. Owned dogs were more likely male, and non-pedigree or local breed. These households kept their dogs either fully restricted, semi-free roaming or free-roaming but full restriction was reported only at the urban site. Dog bite cases were reported to be higher at the urban site, and commonly affected children/young adults to 20 years old and males. A higher number of unowned dogs was observed at the urban site than at the rural site. Data generated within these surveys can inform rabies risk assessment models to quantify the probability of rabies being released into Lombok and resulting in the infection of the local dog population. The information gained is critical for efforts to educate dog owners about rabies, as a component of preparedness to prevent the establishment of rabies should an incursion occur. PMID:25932916

  11. Transthoracic lung ultrasound in normal dogs and dogs with cardiogenic pulmonary edema: a pilot study.

    Science.gov (United States)

    Rademacher, Nathalie; Pariaut, Romain; Pate, Julie; Saelinger, Carley; Kearney, Michael T; Gaschen, Lorrie

    2014-01-01

    Pulmonary edema is the most common complication of left-sided heart failure in dogs and early detection is important for effective clinical management. In people, pulmonary edema is commonly diagnosed based on transthoracic ultrasonography and detection of B line artifacts (vertical, narrow-based, well-defined hyperechoic rays arising from the pleural surface). The purpose of this study was to determine whether B line artifacts could also be useful diagnostic predictors for cardiogenic pulmonary edema in dogs. Thirty-one normal dogs and nine dogs with cardiogenic pulmonary edema were prospectively recruited. For each dog, presence or absence of cardiogenic pulmonary edema was based on physical examination, heartworm testing, thoracic radiographs, and echocardiography. A single observer performed transthoracic ultrasonography in all dogs and recorded video clips and still images for each of four quadrants in each hemithorax. Distribution, sonographic characteristics, and number of B lines per thoracic quadrant were determined and compared between groups. B lines were detected in 31% of normal dogs (mean 0.9 ± 0.3 SD per dog) and 100% of dogs with cardiogenic pulmonary edema (mean 6.2 ± 3.8 SD per dog). Artifacts were more numerous and widely distributed in dogs with congestive heart failure (P dogs. © 2014 American College of Veterinary Radiology.

  12. Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs

    Science.gov (United States)

    Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

    2012-01-01

    Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon. PMID:22293095

  13. Complex population structure in African village dogs and its implications for inferring dog domestication history

    OpenAIRE

    Boyko, Adam R.; Boyko, Ryan H.; Boyko, Corin M.; Parker, Heidi G.; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D.; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A.; Schoenebeck, Jeffrey; Todhunter, Rory J.; Jones, Paul; Bustamante, Carlos D.

    2009-01-01

    High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318...

  14. [Age-related characteristics of the surface bioelectrical potential of human, canine and rat teeth and features of its distribution over the surface of the crown].

    Science.gov (United States)

    Donskiĭ, G I; Pavliuchenko, O N; Palamarchuk, Iu N; Makarova, N Ia

    1989-01-01

    Using a digital electron voltmeter, bioelectrical potentials (BEPs) of dental crowns have been recorded in 180 patients, 36 dogs, and 93 white non-inbred rats. It has been established that the surface BEP is a marker of dental enamel maturation and does not depend on the species of mammals. On the other hand maturation processes differ in their rate on the cutting edge, equator, and neck: with advancing age algebraic difference between the magnitudes of surface BEPs decreases in humans and increases in dogs and rats.

  15. Toxicity of inhaled Ca-DTPA in the beagle dog

    International Nuclear Information System (INIS)

    Smith, V.H.; Ragan, H.A.; Lund, J.E.; Hackett, P.L.

    1975-01-01

    There are several advantages to the administration of Ca- DTPA by inhalation rather than intravenous drip for the decorporation of certain radionuclides. Among these are the possibility of treating very promptly following an accidental incorporation to achieve maximum treatment effectiveness and convenince for medical management, even to the extent that treatment can be self-administered. The present investigational New Drug permit allows treatment of humans only by the intravenous route and animal studies are required to justify the new route. Earlier work in rats and hamsters showed five successive daily inhalations of Ca-DTPA aerosols (dose 1 to 4 times human i.v. dose) produced a transitory emphysema in 17/40 rats serially sacrificed up to 3 weeks following the last exposure and in 10/20 hamsters up to 1 week after exposure. No emphysema was seen in rats sacrificed after 3 weeks and in hamsters after 1 week following the exposures. Results of tests in dogs administered DTPA by inhalation showed hyperplasia of the gastric submucosal lymphoid follicles observed 1 week following the last exposure may be treatment-related, but other observed changes were considered unrelated. (U.S.)

  16. Developmental-stage-dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses

    International Nuclear Information System (INIS)

    Hoshino, K.; Kameyama, Y.

    1988-01-01

    Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats

  17. Tooele Army Depot Revised Final Site-Wide Ecological Risk Assessment. Volume IV.

    Science.gov (United States)

    1998-02-01

    SS!5!55 "^ **i "i *n Q ti ti d ci *»S «S «n *n «n 6 Ö Ö «*$ «ri «r> *r) Wj «1 «rj o c> o <a fr^ «•! *rj f) rrj «*j fry ...Venugopal and Luckey 1978. Arsenic 0.94 (mouse, AsIII and AsV) 0.95 (dog, AsV) 60 - 90 (rat) 2.5 ( chicken ) 2.4 (dog) 0.0077-0.012 0.277 0.288...reservation. A pan of that investigation involves a search for rare plant species, those that might be included under stipulations of the Endangered

  18. N-isopropyl-[123I]p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

    International Nuclear Information System (INIS)

    Winchell, H.S.; Horst, W.D.; Braun, L.; Oldendorf, W.H.; Hattner, R.; Parker, H.

    1980-01-01

    The kinetics of N-isopropyl-p-[ 123 I]iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours. The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism

  19. Communication between domestic dogs (Canis familiaris) and humans: dogs are good learners.

    Science.gov (United States)

    Elgier, Angel M; Jakovcevic, Adriana; Barrera, Gabriela; Mustaca, Alba E; Bentosela, Mariana

    2009-07-01

    Communication involves a wide range of behaviours that animals emit in their daily lives and can take place between different species, as is the case of domestic dogs (Canis familiaris) and humans. Dogs have shown to be successful at following human cues to solve the object choice task. The question is what are the mechanisms involved in these communicative abilities. This article presents a review of studies about the communicative capacities of domestic dogs emphasizing the ones that considered the effect of associative learning upon these skills. In addition, evidence about differences in dogs' performance in following physical or social cues is summarized and two studies where both signals compete are presented here. The obtained results suggest that the training of a colour cue reverses the dogs' preference for the social one. These results are discussed in light of the findings that gave importance to the learning effect, concluding that the dogs fundamentally follow those cues that allowed them to obtain reinforcers in their previous learning history.

  20. Comparison between cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs.

    Science.gov (United States)

    Gaitero, Luis; Nykamp, Stephanie; Daniel, Rob; Monteith, Gabrielle

    2013-01-01

    Cranial thoracic intervertebral disc herniations have been reported to be rare in dogs due to the presence of the intercapital ligament, however some studies have proposed they may not be uncommon in German Shepherd dogs. The purpose of this retrospective study was to compare cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs (control group). Medical records at the Ontario Veterinary College were searched for German Shepherd dogs and other large breed dogs that had magnetic resonance imaging studies including the T1-T9 region. For each dog and each disc space from T1-T9, three variables (compression, disc degeneration, and herniation) were recorded and graded based on review of sagittal T2-weighted images. Twenty-three German Shepherd dogs and 47 other large breed dogs met inclusion criteria. The German Shepherd dog group had higher scores than the control group for compression (P = 0.0099) and herniation (P dog group, intervertebral discs T2-T3 and T4-T5 had an increased risk for compression and T3-T4 had an increased risk for compression and herniation. Findings from this study indicated that German Shepherd dogs may be more likely than other large breed dogs to have spinal cord compression due to cranial thoracic disc herniations. Imaging of the cranial thoracic spine, including T2-T3, is recommended for German Shepherd dogs with T3-L3 neurological signs. © 2012 Veterinary Radiology & Ultrasound.

  1. Cystic meningiomas in 2 dogs

    International Nuclear Information System (INIS)

    Bagley, R.S.; Kornegay, J.N.; Lane, S.B.; Thrall, D.L.; Page, R.L.

    1996-01-01

    Two dogs with signs of forebrain disease had hypodense lesions on computed tomography evaluation. Magnetic resonance imaging of the first dog showed a hypointense lesion on the T1-weighted scan and a hyperintense lesion on T2-weighted scanning. At surgery, both dogs had a primary cystic intracranial lesion, and the abnormal tissue adjacent to the cyst had histological features of meningioma. Each dog underwent whole brain irradiation after surgery, and 1 dog lived for 3 years after treatment. While uncommon, meningioma should be considered as a differential diagnosis in dogs with cystic intracranial lesions

  2. Human perception of fear in dogs varies according to experience with dogs.

    Directory of Open Access Journals (Sweden)

    Michele Wan

    Full Text Available To investigate the role of experience in humans' perception of emotion using canine visual signals, we asked adults with various levels of dog experience to interpret the emotions of dogs displayed in videos. The video stimuli had been pre-categorized by an expert panel of dog behavior professionals as showing examples of happy or fearful dog behavior. In a sample of 2,163 participants, the level of dog experience strongly predicted identification of fearful, but not of happy, emotional examples. The probability of selecting the "fearful" category to describe fearful examples increased with experience and ranged from.30 among those who had never lived with a dog to greater than.70 among dog professionals. In contrast, the probability of selecting the "happy" category to describe happy emotional examples varied little by experience, ranging from.90 to.93. In addition, the number of physical features of the dog that participants reported using for emotional interpretations increased with experience, and in particular, more-experienced respondents were more likely to attend to the ears. Lastly, more-experienced respondents provided lower difficulty and higher accuracy self-ratings than less-experienced respondents when interpreting both happy and fearful emotional examples. The human perception of emotion in other humans has previously been shown to be sensitive to individual differences in social experience, and the results of the current study extend the notion of experience-dependent processes from the intraspecific to the interspecific domain.

  3. Dogs and their human companions: the effect of familiarity on dog-human interactions.

    Science.gov (United States)

    Kerepesi, Andrea; Dóka, Antal; Miklósi, Ádám

    2015-01-01

    There are few quantitative examinations of the extent to which dogs discriminate between familiar and unfamiliar persons. In our study we have investigated whether dogs show differential behaviour towards humans of different degrees of familiarity (owner, familiar person, unfamiliar person). Dogs and humans were observed in eight test situations: (1) Three-way strange situation test, (2) Calling in from food, (3) Obedience test, (4) Walking away, (5) Threatening approach, (6) Playful interaction, (7) Food inhibition test and (8) Manipulation of the dog's body. Dogs distinguished between the owner and the two other test partners in those tests which involved separation from the owner (Test 1, 4), were aversive for the dog (Test 5) or involved playing interaction (Test 6). Our results revealed that the owner cannot be replaced by a familiar person in situations provoking elevated anxiety and fear. In contrasts, dogs did not discriminate between the owner and the familiar person in those tests that were based on obedient behaviour or behaviour towards an assertive person (Tests 2, 3, 7 and 8). Dogs' former training experience reduced the difference between their behaviour towards the owner and the familiar person in situations requiring obedience but it did not mask it totally. The dogs' behaviour towards each of the humans participating in the tests was consistent all over the test series. In summary, dogs discriminated between their owner and the unfamiliar person and always preferred the owner to the unfamiliar person. However, the discrimination between the owner and the familiar person is context-specific. This article is part of a Special Issue entitled: Canine Behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

    Science.gov (United States)

    Furrow, E; Jaeger, J Q; Parker, V J; Hinchcliff, K W; Johnson, S E; Murdoch, S J; de Boer, I H; Sherding, R G; Brunzell, J D

    2016-06-01

    Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Review on dog rabies vaccination coverage in Africa: a question of dog accessibility or cost recovery?

    Science.gov (United States)

    Jibat, Tariku; Hogeveen, Henk; Mourits, Monique C M

    2015-02-01

    Rabies still poses a significant human health problem throughout most of Africa, where the majority of the human cases results from dog bites. Mass dog vaccination is considered to be the most effective method to prevent rabies in humans. Our objective was to systematically review research articles on dog rabies parenteral vaccination coverage in Africa in relation to dog accessibility and vaccination cost recovery arrangement (i.e.free of charge or owner charged). A systematic literature search was made in the databases of CAB abstracts (EBSCOhost and OvidSP), Scopus, Web of Science, PubMed, Medline (EBSCOhost and OvidSP) and AJOL (African Journal Online) for peer reviewed articles on 1) rabies control, 2) dog rabies vaccination coverage and 3) dog demography in Africa. Identified articles were subsequently screened and selected using predefined selection criteria like year of publication (viz. ≥ 1990), type of study (cross sectional), objective(s) of the study (i.e. vaccination coverage rates, dog demographics and financial arrangements of vaccination costs), language of publication (English) and geographical focus (Africa). The selection process resulted in sixteen peer reviewed articles which were used to review dog demography and dog ownership status, and dog rabies vaccination coverage throughout Africa. The main review findings indicate that 1) the majority (up to 98.1%) of dogs in African countries are owned (and as such accessible), 2) puppies younger than 3 months of age constitute a considerable proportion (up to 30%) of the dog population and 3) male dogs are dominating in numbers (up to 3.6 times the female dog population). Dog rabies parenteral vaccination coverage was compared between "free of charge" and "owner charged" vaccination schemes by the technique of Meta-analysis. Results indicate that the rabies vaccination coverage following a free of charge vaccination scheme (68%) is closer to the World Health Organization recommended coverage rate

  6. Social behaviour of domestic dogs (Canis familiaris) in a public off-leash dog park.

    Science.gov (United States)

    Howse, Melissa S; Anderson, Rita E; Walsh, Carolyn J

    2018-03-13

    This study examines the activity budgets and social behaviours initiated and received by 69 focal dogs in an off-leash dog park for 400 s after entry, a time of high activity about which little is known. Using motivationally-neutral labels for social behaviour categories, we describe the frequency of behaviours, and correlations among them. We then examine these relationships in the context of proposed functions for some behaviours in dogs, in terms of information gathering and communication, including visual and tactile signalling. Time spent with other dogs decreased rapidly over the visit, and much of this early interaction involved greeting the park newcomer. Snout-muzzle contact behaviours were ubiquitous, while other behaviours were rarely observed, including aggressive behaviours. Correlations among certain non-contact behaviours initiated and received by focal dogs are consistent with their function as visual signals that may influence the continuation and form of social interactions, and their possible role in social mimicry (i.e., play bow and pull-rear away). Age, sex, and number of dogs present in the park influenced specific aspects of dogs' activity budgets, and a few behaviours. This ethological study provides fundamental data on dog social behaviour in dog parks, about which surprisingly little has been published. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Lessons learned from cloning dogs.

    Science.gov (United States)

    Kim, M J; Oh, H J; Kim, G A; Park, J E; Park, E J; Jang, G; Ra, J C; Kang, S K; Lee, B C

    2012-08-01

    The aim of this article is to review dog cloning research and to suggest its applications based on a discussion about the normality of cloned dogs. Somatic cell nuclear transfer was successfully used for production of viable cloned puppies despite limited understanding of in vitro dog embryo production. Cloned dogs have similar growth characteristics to those born from natural fertilization, with no evidence of serious adverse effects. The offspring of cloned dogs also have similar growth performance and health to those of naturally bred puppies. Therefore, cloning in domestic dogs can be applied as an assisted reproductive technique to conserve endangered species, to treat sterile canids or aged dogs, to improve reproductive performance of valuable individuals and to generate disease model animals. © 2012 Blackwell Verlag GmbH.

  8. Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.

    Science.gov (United States)

    Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A

    2017-08-19

    We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.

  9. Differentiation of minute virus of mice and mouse parvovirus by high resolution melting curve analysis.

    Science.gov (United States)

    Rao, Dan; Wu, Miaoli; Wang, Jing; Yuan, Wen; Zhu, Yujun; Cong, Feng; Xu, Fengjiao; Lian, Yuexiao; Huang, Bihong; Wu, Qiwen; Chen, Meili; Zhang, Yu; Huang, Ren; Guo, Pengju

    2017-12-01

    Murine parvovirus is one of the most prevalent infectious pathogens in mouse colonies. A specific primer pair targeting the VP2 gene of minute virus of mice (MVM) and mouse parvovirus (MPV) was utilized for high resolution melting (HRM) analysis. The resulting melting curves could distinguish these two virus strains and there was no detectable amplification of the other mouse pathogens which included rat parvovirus (KRV), ectromelia virus (ECT), mouse adenovirus (MAD), mouse cytomegalovirus (MCMV), polyoma virus (Poly), Helicobactor hepaticus (H. hepaticus) and Salmonella typhimurium (S. typhimurium). The detection limit of the standard was 10 copies/μL. This study showed that the PCR-HRM assay could be an alternative useful method with high specificity and sensitivity for differentiating murine parvovirus strains MVM and MPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Phylogenetic Distinctiveness of Middle Eastern and Southeast Asian Village Dog Y Chromosomes Illuminates Dog Origins

    Science.gov (United States)

    Brown, Sarah K.; Pedersen, Niels C.; Jafarishorijeh, Sardar; Bannasch, Danika L.; Ahrens, Kristen D.; Wu, Jui-Te; Okon, Michaella; Sacks, Benjamin N.

    2011-01-01

    Modern genetic samples are commonly used to trace dog origins, which entails untested assumptions that village dogs reflect indigenous ancestry or that breed origins can be reliably traced to particular regions. We used high-resolution Y chromosome markers (SNP and STR) and mitochondrial DNA to analyze 495 village dogs/dingoes from the Middle East and Southeast Asia, along with 138 dogs from >35 modern breeds to 1) assess genetic divergence between Middle Eastern and Southeast Asian village dogs and their phylogenetic affinities to Australian dingoes and gray wolves (Canis lupus) and 2) compare the genetic affinities of modern breeds to regional indigenous village dog populations. The Y chromosome markers indicated that village dogs in the two regions corresponded to reciprocally monophyletic clades, reflecting several to many thousand years divergence, predating the Neolithic ages, and indicating long-indigenous roots to those regions. As expected, breeds of the Middle East and East Asia clustered within the respective regional village dog clade. Australian dingoes also clustered in the Southeast Asian clade. However, the European and American breeds clustered almost entirely within the Southeast Asian clade, even sharing many haplotypes, suggesting a substantial and recent influence of East Asian dogs in the creation of European breeds. Comparison to 818 published breed dog Y STR haplotypes confirmed this conclusion and indicated that some African breeds reflect another distinct patrilineal origin. The lower-resolution mtDNA marker consistently supported Y-chromosome results. Both marker types confirmed previous findings of higher genetic diversity in dogs from Southeast Asia than the Middle East. Our findings demonstrate the importance of village dogs as windows into the past and provide a reference against which ancient DNA can be used to further elucidate origins and spread of the domestic dog. PMID:22194840

  11. Food engorgement in 35 dogs (2009-2013) compared with 36 dogs with gastric dilation and volvulus.

    Science.gov (United States)

    Smart, Lisa; Reese, Shona; Hosgood, Giselle

    2017-11-25

    The clinical features and management of food engorgement (FE) in dogs have not been previously described. This retrospective observational study describes characteristics and outcome of 35 dogs with FE, and compares features on presentation to 36 dogs with gastric dilation and volvulus (GDV). Cases were retrospectively reviewed for history, clinical findings and outcome. Gastric distension was measured by caudal gastric margin (CGM), level with lumbar vertebrae, on a lateral abdominal radiograph. Frequent characteristics of dogs with FE included tachycardia, tachypnoea, hyperproteinaemia, increased base excess (BE), mild hypernatraemia and hyperlactataemia. There was overlap in CGM between dogs with GDV (CGM range L3 to >L6) and dogs with FE (CGM range dogs with GDV, lactate concentration in dogs with FE was not associated with CGM or BE. Dogs with FE mostly received medical intervention consisting of fluid therapy and analgesia, and all dogs survived to discharge. In conclusion, dogs with FE frequently presented with acid-base and electrolyte derangements, including hyperlactataemia. While dogs with FE can have gastric distension as severe as that seen with GDV, outcome with supportive care only is excellent. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. The association between dog ownership or dog walking and fitness or weight status in childhood.

    Science.gov (United States)

    Westgarth, C; Boddy, L M; Stratton, G; German, A J; Gaskell, R M; Coyne, K P; Bundred, P; McCune, S; Dawson, S

    2017-12-01

    Health benefits of dog walking are established in adults: dog owners are on average more physically active, and those walking their dogs regularly have lower weight status than those who do not. However, there has been little research on children. This study aimed to examine the association between dog ownership or dog walking and childhood fitness or weight status. A survey of pet ownership and involvement in dog walking was combined with fitness and weight status measurements of 1021 9 to 10-year-old children in the Liverpool SportsLinx study. We found little evidence to support that children who live with, or walk with, dogs are any fitter or less likely to be obese than those who do not. This is an important finding, as it suggests that the activity that children currently do with dogs is not sufficient enough to impact weight status or fitness. © 2016 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

  13. Nonverbal Communication and Human–Dog Interaction

    DEFF Research Database (Denmark)

    Meyer, Iben Helene Coakley; Forkman, Björn

    2014-01-01

    Human–dog interaction relies to a large extent on nonverbal communication, and it is therefore plausible that human sensitivity to nonverbal signals affects interactions between human and dog. Experience with dogs is also likely to influence human–dog interactions, and it has been suggested...... and answered a questionnaire on their experience with dogs. The data obtained were then used to investigate the relationship between experience with dogs and sensitivity to human nonverbal communication. The results did not indicate that experience with dogs improves human nonverbal sensitivity. In study 2, 16...... that it influences human social skills. The present study investigated possible links between human nonverbal sensitivity, experience with dogs, and the quality of human–dog interactions. Two studies are reported. In study 1, 97 veterinary students took a psychometric test assessing human nonverbal sensitivity...

  14. Mitral stenosis in 15 dogs

    International Nuclear Information System (INIS)

    Lehmkuhl, L.B.; Ware, W.A.; Bonagura, J.D.

    1994-01-01

    Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age

  15. Highly Educated Men Establish Strong Emotional Links with Their Dogs: A Study with Monash Dog Owner Relationship Scale (MDORS) in Committed Spanish Dog Owners

    Science.gov (United States)

    Bulbena, Antoni; Tobeña, Adolf

    2016-01-01

    The characteristics of the human-animal bond may be influenced by both owner-related and dog-related factors. A study was designed to explore the existence of different dog ownership patterns and their related factors. We created an on line questionnaire that included demographic questions about the dog and the owner, a Spanish version of the Monash Dog Owner Relationship Scale (MDORS) and a validated measure of satisfaction with life (Cantril’s ladder). We collected 1140 valid responses from adult dog owners, who were recruited using the client databases of Spanish veterinary practices. We explored the presence of groups within the population using Principal Components Analysis (PCA) of the MDORS variables combined with Hierarchical Cluster Analysis (HCA). Two groups were found; Group I having a higher level of emotional involvement with their dogs compared with Group II. Binary logistic regression was used to explore demographic factors that influenced group membership. Four variables were significantly associated with membership of Group I (pdog-ownership may be present within a population of owner-dog dyads, and that certain owner characteristics are associated with the type of owner-dog relationship. Future research could apply a similar approach to different types of sample population in order to identify specific patterns of dog-ownership. PMID:28033397

  16. Highly Educated Men Establish Strong Emotional Links with Their Dogs: A Study with Monash Dog Owner Relationship Scale (MDORS) in Committed Spanish Dog Owners.

    Science.gov (United States)

    Calvo, Paula; Bowen, Jonathan; Bulbena, Antoni; Tobeña, Adolf; Fatjó, Jaume

    2016-01-01

    The characteristics of the human-animal bond may be influenced by both owner-related and dog-related factors. A study was designed to explore the existence of different dog ownership patterns and their related factors. We created an on line questionnaire that included demographic questions about the dog and the owner, a Spanish version of the Monash Dog Owner Relationship Scale (MDORS) and a validated measure of satisfaction with life (Cantril's ladder). We collected 1140 valid responses from adult dog owners, who were recruited using the client databases of Spanish veterinary practices. We explored the presence of groups within the population using Principal Components Analysis (PCA) of the MDORS variables combined with Hierarchical Cluster Analysis (HCA). Two groups were found; Group I having a higher level of emotional involvement with their dogs compared with Group II. Binary logistic regression was used to explore demographic factors that influenced group membership. Four variables were significantly associated with membership of Group I (pdog-ownership may be present within a population of owner-dog dyads, and that certain owner characteristics are associated with the type of owner-dog relationship. Future research could apply a similar approach to different types of sample population in order to identify specific patterns of dog-ownership.

  17. Near-term and late biological effects of acute and low-dose-rate continuous gamma-ray exposure in dogs and monkeys

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.

    1979-07-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (inury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with gamma rays at 35 r/day until death to determine the amount of radiation-induced injry remaining in conditioned animals as a reduction in mean survival time. Dogs (50%) and monkeys (8%) died from injury incurred during conditioning exposures. Thus, the comparative response (in terms of lethality) of dogs and monkeys to dose protraction by acute dose fractionation was similar to what we would expect from a single acute dose. The mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approx. 1400 h). Thus, the hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35-R/day gamma-ray challenge exposure were greater (significant in dogs but not in monkeys) than for their control counterparts. Thus, long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than 4 times the acute LD 50 30 in dogs and approximately 2 times that in monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 Rat/day

  18. Identification of a third form of NaK-ATPase catalytic subunit in rat brain by photoaffinity labeling

    International Nuclear Information System (INIS)

    Lowndes, J.M.; Millan, N.M.; Ruoho, A.E.; Hokin-Neaverson, M.

    1987-01-01

    Using photoaffinity labeling, they have found a form of the NaK-ATPase catalytic subunit, α(-), in the rat brain that is distinct from the α and α(+) forms. Strong radiolabeling of α(-) was obtained with [ 125 I]azido-iodophenethylamido-succinyl-cymarin (AISC). AISC is a new cardiotonic steroid photolabel which they have synthesized and characterized chemically and biochemically. This compound labels α(-) better than the photolabels that they have previously reported. SDS-PAGE (5%) of photolabeled rat brain microsomes showed that α(-) migrated with faster mobility than the dog kidney α subunit. The α(-) appears to have different specificity for different cardiotonic steroids than either α(+) or α. The radiolabeling of rat brain α(+) and dog kidney α with [ 125 I]AISC was protectable by ouabain; in contrast, 1 mM ouabain did not reduce the [ 125 I]AISC-labeling of α(-), although the labeling was protected with 200 μM cymarin or AISC. The results indicate that the α(-) form of the NaK-ATPase in rat brain binds cymarin and its derivative but has little affinity for ouabain. It is possible that α(-) may be the translation product of the rat brain α(III) mRNA which has recently been described

  19. Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs

    Directory of Open Access Journals (Sweden)

    Lieske Camilla L

    2011-12-01

    Hg ratios were not similar to human concentrations and ratios, the sled dog toxicokinetics of Hg in blood, was more similar to that of humans than traditional laboratory animals (such as the rat.

  20. Ureterocolonic anastomosis in clinically normal dogs

    International Nuclear Information System (INIS)

    Stone, E.A.; Walter, M.C.; Goldschmidt, M.H.; Biery, D.N.; Bovee, K.C.

    1988-01-01

    Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degress of metabolic acidosis, hyperammonemia, and neurologic disease may result

  1. Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs.

    Science.gov (United States)

    Hanson, J M; Tengvall, K; Bonnett, B N; Hedhammar, Å

    2016-01-01

    Naturally occurring adrenocortical insufficiency (NOAI) in dogs is considered an uncommon disease with good prognosis with hormonal replacement treatment. However, there are no epidemiological studies with estimates for the general dog population. To investigate the epidemiological characteristics of NOAI in a large population of insured dogs. Data were derived from 525,028 client-owned dogs insured by a Swedish insurance company representing 2,364,652 dog-years at risk (DYAR) during the period between 1995-2006. Retrospective cohort study. Incidence rates, prevalences, and relative risks for dogs with NOAI (AI with no previous claim for hypercortisolism), were calculated for the whole dog population, and for subgroups divided by breed and sex. Mortality rates were calculated and compared in dogs with NOAI and the remaining dogs overall. In total 534 dogs were identified with NOAI. The overall incidence was 2.3 cases per 10,000 DYAR. The relative risk of disease was significantly higher in the Portuguese Water Dog, Standard Poodle, Bearded Collie, Cairn Terrier, and Cocker Spaniel compared with other breeds combined. Female dogs overall were at higher risk of developing AI than male dogs (RR 1.85; 95% CI, 1.55-2.22; P dogs with NOAI than in dogs overall. The data supports the existence of breed-specific differences in incidence rates of NOAI in dogs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. Dog ownership and dog walking to promote physical activity and health in patients.

    Science.gov (United States)

    Epping, Jacqueline N

    2011-07-01

    Lack of physical activity is a significant risk factor for many chronic diseases and conditions and is associated with significant medical costs. Approximately half of adults and more than a third of adolescents and youth in the United States do not achieve recommended levels of physical activity. Effective population-level strategies are needed to promote activities that are practical, accessible, and sustainable and that can reach a large proportion of the population. Dog walking may be such a strategy. Walking is popular, easy, and sustainable and has a low risk of injury. Owning dogs confers many health benefits, and dog walking, in particular, can help promote physical activity and improve health. Physicians and other health care providers can play a unique and integral role in promoting physical activity among patients by recommending dog walking both to dog owners and to non-dog owners as a purposeful, enjoyable, and sustainable form of regular physical activity.

  3. Characterisation of Cdkl5 transcript isoforms in rat.

    Science.gov (United States)

    Hector, Ralph D; Dando, Owen; Ritakari, Tuula E; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

    2017-03-01

    CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically and experimentally, the rat Cdkl5 gene structure and its associated transcript isoforms. New exonic regions, splice sites and UTRs are described, confirming the presence of four distinct transcript isoforms. The predominant isoform in the brain, which we name rCdkl5_1, is orthologous to the human hCDKL5_1 and mouse mCdkl5_1 isoforms and is the most highly expressed isoform across all brain regions tested. This updated gene model of Cdkl5 in rat provides a framework for studies into its protein products and provides a reference for the development of molecular therapies for testing in rat models of CDKL5 disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A consensus definition of cataplexy in mouse models of narcolepsy.

    Science.gov (United States)

    Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

  5. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

    Directory of Open Access Journals (Sweden)

    Marie E Barabas

    Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is

  6. TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

    Science.gov (United States)

    Stucky, Cheryl L.

    2012-01-01

    Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed

  7. Do Dogs Provide Information Helpfully?

    Science.gov (United States)

    Piotti, Patrizia; Kaminski, Juliane

    2016-01-01

    Dogs are particularly skilful during communicative interactions with humans. Dogs’ abilities to use human communicative cues in cooperative contexts outcompete those of other species, and might be the result of selection pressures during domestication. Dogs also produce signals to direct the attention of humans towards outside entities, a behaviour often referred to as showing behaviour. This showing behaviour in dogs is thought to be something dogs use intentionally and referentially. However, there is currently no evidence that dogs communicate helpfully, i.e. to inform an ignorant human about a target that is of interest to the human but not to the dog. Communicating with a helpful motive is particularly interesting because it might suggest that dogs understand the human’s goals and need for information. In study 1, we assessed whether dogs would abandon an object that they find interesting in favour of an object useful for their human partner, a random novel distractor, or an empty container. Results showed that it was mainly self-interest that was driving the dogs’ behaviour. The dogs mainly directed their behaviour towards the object they had an interest in, but dogs were more persistent when showing the object relevant to the human, suggesting that to some extent they took the humans interest into account. Another possibility is that dogs’ behaviour was driven by an egocentric motivation to interact with novel targets and that the dogs’ neophila might have masked their helpful tendencies. Therefore, in study 2 the dogs had initial access to both objects, and were expected to indicate only one (relevant or distractor). The human partner interacted with the dog using vocal communication in half of the trials, and remaining silent in the other half. Dogs from both experimental groups, i.e. indicating the relevant object or indicating the distractor, established joint attention with the human. However, the human’s vocal communication and the presence

  8. The cerebrovascular structure and brain tissue volume: a comparative study between beagle dogs and mongrel dogs

    International Nuclear Information System (INIS)

    Liu Sheng; Shi Haibin; Hu Weixing; Zu Qingquan; Lu Shanshan; Xu Xiaoquan; Sun Lei; Li Linsun

    2011-01-01

    Objective: To compare the differences of cerebrovascular structure and brain tissue volume between beagle and mongrel dogs by using angiography and MR scanning. Methods: A total of 40 dogs, including 20 beagle dogs (beagle group) and 20 mongrel dogs (mongrel group), were enrolled in this study. Under general anesthesia, all dogs were examined with cerebral angiography and MR scanning. The cerebrovascular structure was evaluated with angiography via selective catheterization of aortic arch, bilateral external cerebral arteries (ECA), maxillary arteries, internal cerebral arteries (ICA) and vertebral arteries separately. The diameters of the ICA, middle cerebral artery (MCA), rostral cerebral artery (RCA), the anastomosis channel ICA and ECA, and basilar artery (BA) were measured at the similar point of each dog. Meanwhile the volumes of the brain tissue were calculated in coronal T2 view of MR scanning. The statistical analysis was performed among the weight of dogs, the diameter of arteries and the volume of brain tissue. The differences in the diameters and brain tissue volume were compared between the two groups. Results: No obvious variations in the cerebrovascular structure and brain tissue volume were found in these dogs. One mongrel dog was excluded from this study because of the severe stenosis of ICA. The mean weight of 20 beagle dogs and 19 mongrel dogs was (12.81±1.29) kg and (12.85±1.12) kg, respectively. The diameters of the ICA, MCA, RCA, the anastomosis channel between ICA and ECA and BA in beagle group were (1.26±0.07) mm, (0.90±0.05) mm, (0.58±0.07) mm, (0.55±0.07) mm and (0.95±0.06) mm, respectively. These parameters in mongrel group were (1.27±0.07) mm, (0.92±0.05) mm, (0.59±0.06) mm, (0.67±0.07) mm and (0.94±0.05) mm, respectively. The volume of brain in two groups was (76232.33±5018.51) mm 3 and (71863.96±4626.87) mm 3 , respectively. There were no obvious correlation among the body weight, the cerebrovascular diameters and brain

  9. Beware of the dog? An observational study of dog-related musculoskeletal injury in the UK.

    Science.gov (United States)

    Willmott, H; Greenheld, N; Goddard, R

    2012-05-01

    Although owning a dog confers numerous health benefits, dogs can cause falls resulting in musculoskeletal injury and fractures. We conducted a prospective observational study over a two-month period to investigate the incidence and epidemiology of dog-related musculoskeletal injury. All patients attending the Emergency Department, trauma ward or fracture clinic were asked whether their injury was caused by a dog. Thirty-seven patients were identified. There were 26 fractures, 10 soft-tissue injuries and one head injury. Seventeen patients were admitted to the hospital and sixteen cases required an operation. Older people were statistically more likely to sustain a fracture (p=0.0003) or require hospital admission (p=0.02). Mechanisms of injury are discussed and can be classified into direct or indirectly caused by the dog. The most common injury mechanism was being pulled over by a dog on a lead. Injury avoidance strategies are discussed. We conclude that dogs are a potential hazard, particularly to the elderly and the morbidity associated with these injuries may offset the health benefits conferred by dog ownership. Copyright © 2012. Published by Elsevier Ltd.

  10. VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS COMPARED TO DOGS WITH HYPERADRENOCORTICISM.

    Science.gov (United States)

    Granger, L Abbigail; Hilferty, Michael; Francis, Taylor; Steiner, Jörg M; Gaschen, Lorrie

    2015-01-01

    Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy dogs on ultrasound examination and the prevalence and clinical significance of this finding is unknown. The objective of this study was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and correlate these findings to weight, age, and body condition score (BCS). An additional objective was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and weight were recorded. Dogs were screened for health by physical examination, serum chemistry panel, urine specific gravity, and a canine pancreatic lipase immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism were also reviewed and pancreatic echogenicity and echotexture were recorded. The prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and heterogeneity was 40% (30 of 74). No correlation existed between pancreatic echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically significant increase in the proportion of dogs having a hyperechoic pancreas was found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P pancreas in these samples confounds interpretation of diseases such as chronic pancreatitis. © 2015 American College of Veterinary Radiology.

  11. Size and demography pattern of the domestic dog population in Bhutan: Implications for dog population management and disease control.

    Science.gov (United States)

    Rinzin, Karma; Tenzin, Tenzin; Robertson, Ian

    2016-04-01

    Understanding the demography of domestic dogs is essential to plan the dog population management and rabies control program. In this study, we estimated the owned and stray dog population and the proportion of owned dogs that are free-roaming in Bhutan. For this, a cross-sectional household surveys were conducted in six districts (both urban and rural areas) and two border towns in southern Bhutan. The population estimation was done by extrapolation of the mean number of dogs per household and dogs per person, whilst mark-resight survey was conducted to estimate the proportion of owned dogs that were free-roaming. A total of 1,301 (rural:585; urban:716) respondents (one per household) were interviewed of which 173 households (24.4%) in urban areas owned 237 dogs whilst 238 households (40.8%) in rural areas owned 353 dogs. The mean number of dogs per dog owning household was estimated to be 1.44 (urban:1.37 dogs; rural:1.48 dogs) and dogs per household was estimated to be 0.45 (urban:0.33; rural:0.60). The dog: human ratio was 1:16.30 (0.06 dogs per person) in urban areas and 1:8.43 (0.12 dogs per person) in rural areas. The total owned dog population based on the mean number of dogs per household and dogs per person were estimated to be 65,312 and 71,245 in the country, respectively. The male: female ratio of the owned dog was 1.31:1 in urban areas and 2.05:1 in rural areas. Majority of the dogs were local non-descript breeds in both urban (60.8%) and rural (78%) areas, and the most common source was acquisition from friends or family (44.7%). The stray dog population in Bhutan was estimated to be 48,379 (urban:22,772; rural:25,607). Of the total estimated owned dog population in the two border towns, the proportion that were found free-roaming was estimated to be 31%. The different dog population estimation methods were compared and discussed in this paper. This study generated baseline data on the demographic patterns of the owned and stray dogs in Bhutan which

  12. Peripheral Nerve Repair and Prevention of Neuroma Formation

    Science.gov (United States)

    2014-09-01

    bone disease in Neurofibromatosis type I. Molecular genetics and metabolism . 2008;94(1):105-11. doi: 10.1016/j.ymgme.2007.12.004. PubMed PMID...isolated from dog, and continue to develop them in a canine model of peripheral nerve extension- repair as well as characterize their contribution...Task 1: To test the functional contribution of the mouse/human cells (athymic rats) and their canine counterpart ( canine ) in critical size nerve

  13. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Azpurua, Jorge; Feigenson, Marina; Bozzella, Michael; Mao, Zhiyong; Catania, Kenneth C; Gorbunova, Vera

    2009-11-17

    The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.

  14. Finding Cardiovascular Disease Genes in the Dog

    Science.gov (United States)

    Parker, Heidi G.; Meurs, Kathryn M.; Ostrander, Elaine A.

    2013-01-01

    Recent advances in canine genomics are changing the landscape of veterinary biology, and by default, veterinary medicine. No longer are clinicians locked into traditional methods of diagnoses and therapy. Rather major advances in canine genetics and genomics from the past five years are now changing the way the veterinarian of the 21st century practices medicine. First, the availability of a dense genome map gives canine genetics a much needed foothold in comparative medicine, allowing advances made in human and mouse genetics to be applied to companion animals. Second, the recently released 7.5x whole genome sequence of the dog is facilitating the identification of hereditary disease genes. Finally, development of genetic tools for rapid screening of families and populations at risk for inherited disease means that the cost of identifying and testing for disease loci will significantly decrease in coming years. Out of these advances will come major changes in companion animal diagnostics and therapy. Clinicians will be able to offer their clients genetic testing and counseling for a myriad of disorders. Such advances are certain to generate healthier and more long lived dogs, improving quality of life for owner and pet alike. The clinician of the 21st century, therefore, faces incredible opportunities as well as challenges in the management of genetic disease. In this review we summarize recent findings in canine genomics and discuss their application to the study of canine cardiac health. PMID:19083345

  15. Dogs with macroadenomas have lower body temperature and heart rate than dogs with microadenomas.

    Science.gov (United States)

    Benchekroun, Ghita; Desquilbet, Loic; Herrtage, Michael E; Jeffery, Nick D; Rosenberg, Dan; Granger, Nicolas

    2017-09-01

    Pituitary macroadenomas compress the hypothalamus, which partly regulates heart rate and body temperature. The aim of this study was to investigate whether heart rate and/or body temperature could aid in clinically differentiating dogs with macroadenomas from dogs with microadenomas (i.e. small non-compressive pituitary mass). Two groups of dogs diagnosed with pituitary-dependent hyperadrenocorticism (i.e. Cushing's disease) were included. Heart rate and body temperature were collected on initial presentation before any procedure. Dogs with macroadenoma had a significantly lower heart rate and body temperature (Pdogs with microadenoma. We suggest that the combined cut-off values of 84 beats per minutes and 38.3°C in dogs with Cushing's disease, especially with vague neurological signs (nine of 12 dogs=75%), might help to suspect the presence of a macroadenoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter mice crossed with a human SNCA transgenic mouse model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Margarita Chumarina

    2017-03-01

    Full Text Available Mouse embryonic stem cell (mESC lines were derived by crossing heterozygous transgenic (tg mice expressing green fluorescent protein (GFP under the control of the rat tyrosine hydroxylase (TH promoter, with homozygous alpha-synuclein (aSYN mice expressing human mutant SNCAA53T under the control of the mouse Prion promoter (MoPrP, or wildtype (WT mice. The expression of GFP and human aSYN was validated by immunocytochemistry in midbrain neuron cultures upon differentiation of mESC lines using stromal cell-derived inducing activity. These mESC lines can help to study the impact of human aSYN expression in neurons and oligodendrocytes, and also trace GFP-expressing midbrain neurons.

  17. Generation of muscular dystrophy model rats with a CRISPR/Cas system.

    Science.gov (United States)

    Nakamura, Katsuyuki; Fujii, Wataru; Tsuboi, Masaya; Tanihata, Jun; Teramoto, Naomi; Takeuchi, Shiho; Naito, Kunihiko; Yamanouchi, Keitaro; Nishihara, Masugi

    2014-07-09

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation. Dmd-mutated rats exhibited a decline in muscle strength, and the emergence of degenerative/regenerative phenotypes in the skeletal muscle, heart, and diaphragm. These mutations were heritable by the next generation, and F1 male rats exhibited similar phenotypes in their skeletal muscles. These model rats should prove to be useful for developing therapeutic methods to treat DMD.

  18. Do dogs live in joint families? Understanding allo-parental care in free-ranging dogs

    OpenAIRE

    Paul, Manabi; Bhadra, Anindita

    2016-01-01

    Cooperative breeding is an excellent example of altruistic cooperation in social groups. Domestic dogs have evolved from cooperatively hunting and breeding ancestors, but have adapted to a facultatively social scavenging lifestyle on streets, and solitary living in human homes. Pets typically breed and reproduce under human supervision, but free-ranging dogs can provide insights into the natural breeding biology of dogs. We conducted a five year long study on parental care of free-ranging dog...

  19. Characterization and autoradiographic visualization of (+)-[3H]SKF10,047 binding in rat and mouse brain: further evidence for phencyclidine/sigma opiate receptor commonality

    International Nuclear Information System (INIS)

    Sircar, R.; Nichtenhauser, R.; Ieni, J.R.; Zukin, S.R.

    1986-01-01

    The binding specificity of (+)-[ 3 H]N-allylnormetazocine, the dextrorotatory isomer of the prototypical sigma opiate SKF10,047, was determined in rat and mouse brain and the neuroanatomical distribution of its binding sites elucidated by quantitative autoradiography in sections of rat brain. Computer-assisted Scatchard analysis revealed an apparent two-site fit of the binding data in both species and in all rat brain regions examined. In whole rat brain, the Kd values were 3.6 and 153 nM and the maximum binding values were 40 fmol and 1.6 pmol/mg of protein for the apparent high- and low-affinity binding sites, respectively. (+)-SKF10,047, haloperidol and pentazocine were among the most potent inhibitors of 7 nM (+)-[ 3 H]SKF10,047 binding to the higher affinity sites; rank orders of ligand potencies at these sites differ sharply from those that have been reported for the [ 3 H]phencyclidine (PCP) site, or for eliciting PCP-like or SKF10,047-like behaviors. By contrast, rank orders of potency of sigma opiods, PCP derivatives and dioxolanes for displacement of 100 nM (+)-[ 3 H]SKF10,047 from the more numerous lower affinity sites in the presence of 100 nM haloperidol agreed closely with their potencies in the [ 3 H]PCP binding assay as well as their potencies in exerting PCP- or SKF10,047-like behavioral effects. In order to compare directly the anatomical localizations of PCP and (+)-SKF10,047 binding sites, quantitative light microscopy autoradiography utilizing tritium-labeled PCP and (+)-SKF10,047 was carried out in rat brain sections. (+)-[ 3 H]SKF10,047 binding was observed to follow the regional pattern of [3H]PCP binding but also to bind in other regions not associated with PCP receptors

  20. Prevalence of Yersinia pestis in rodents and fleas associated with black-tailed prairie dogs (Cynomys ludovicianus) at Thunder Basin National Grassland, Wyoming

    Science.gov (United States)

    Thiagarajan, Bala; Bai, Ying; Gage, Kenneth L.; Cully, Jack F.

    2008-01-01

    Rodents (and their fleas) that are associated with prairie dogs are considered important for the maintenance and transmission of the bacterium (Yersinia pestis) that causes plague. Our goal was to identify rodent and flea species that were potentially involved in a plague epizootic in black-tailed prairie dogs at Thunder Basin National Grassland. We collected blood samples and ectoparasites from rodents trapped at off- and on-colony grids at Thunder Basin National Grassland between 2002 and 2004. Blood samples were tested for antibodies to Y. pestis F-1 antigen by a passive hemagglutination assay, and fleas were tested by a multiplex polymerase chain reaction, for the presence of the plague bacterium. Only one of 1,421 fleas, an Oropsylla hirsuta collected in 2002 from a deer mouse, Peromyscus maniculatus, tested positive for Y. pestis. Blood samples collected in summer 2004 from two northern grasshopper mice, Onychomys leucogaster, tested positive for Y. pestis antibodies. All three positive samples were collected from on-colony grids shortly after a plague epizootic occurred. This study confirms that plague is difficult to detect in rodents and fleas associated with prairie dog colonies, unless samples are collected immediately after a prairie dog die-off.

  1. Psychosocial and Environmental Factors Associated with Dog

    OpenAIRE

    Richards, Elizabeth; McDonough, Megan H; Edwards, Nancy E; Lyle, RM; Troped, Philip J

    2013-01-01

    Dog walking is associated with higher levels of physical activity (PA). However, not all dog owners walk their dog(s) at a level sufficient for health benefits. Therefore, identifying correlates of dog walking may help to inform the design of more effective interventions to promote this specific form of PA. The purpose of this study was to examine psychosocial and environmental correlates of dog walking and relationships of dog walking with overall PA. In 2010, 391 dog owners (Mage= 43.6±12.3...

  2. [Pharmacokinetic of four alkaloids of Yanshu injection in Beagel dogs].

    Science.gov (United States)

    Liu, Jiping; Xue, Mei; Huang, Xin; Wang, Shu; Jiang, Zhenzhou; Zhang, Luyong

    2012-06-01

    For studying the pharmacokinetic of Yanshu injections in Beagel dogs, a sensitive and reproducible LC-MS method for quantitative determination of matrine, oxymatrine, sophocarpine and oxysophocarpine in dog's plasma were developed and validated using monocrotaline as an internal standard after iv of Yanshu injections (Sophorae Flavescentis Radix and Heterosmilacis Japonicae Rhizoma). The separation of plasma samples was performed on a CN column by isocratic elution with methanol-10 mmol x L(-1) NH4Ac-0.02% HCOOH-H2O 90:10 as the mobile phase. The plasma concentration of four kinds of alkaloids were calculated in dog plasta by detection of healthy dogs given Yanshu injection fluid after in twelve hours of plasma samples, All data of concentration-time of four kinds of alkaloids were treated with pharmacokinetics program DAS 2. 0. MT, OMT, SP and OSP have a good linear relationship in 0.01-16.0, 0.02-60.0, 0.01-4.0, 0.02-16.0 mg x L(-1), respectively. The average recoveries were more than 90% and the RSD of precision and stability of the test were less than 6.4% iv 1.2 g x kg(-1) Yanshu injection, four kinds of alkaloids in rats meet the two-compartment open pharmacokinetic model, Cmax and the concentration of the original liquid in the proportion of the basic line, the AUC(0-infinity) of matrine and oxymatrine, sophocarpine and oxysophocarpine compared to the original both in the proportion of liquid increases, the MRT(0-infinity) and t(1/2z) of matrine and sophocarpine were less than oxymatrine and oxysophocarpine; four kinds of alkaloids apparent volume of distribution matrine > oxymatrine, sophocarpine > oxysophocarpine. A method with high recovery rate and good stabilitywas established to determine the blood concentration of MT, OMT, SP, OSP in Yanshu injection and applied in its pharmacokinetics successfully.

  3. Evaluation of pulsatile plasma concentrations of growth hormone in healthy dogs and dogs with dilated cardiomyopathy

    NARCIS (Netherlands)

    Beijerink, N.J.; Lee, W.M.; Stokhof, A.A.; Voorhout, G.; Mol, J.A.; Kooistra, H.S.

    2011-01-01

    Abstract OBJECTIVE: To evaluate plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I) in healthy dogs and large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 8 dogs with DCM and 8 healthy control dogs of comparable age and body weight. PROCEDURES: Blood

  4. Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile.

    Science.gov (United States)

    Jones, Michael D; Rainville, Paul D; Isaac, Giorgis; Wilson, Ian D; Smith, Norman W; Plumb, Robert S

    2014-09-01

    Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. The Blue Dog: evaluation of an interactive software program to teach young children how to interact safely with dogs.

    Science.gov (United States)

    Schwebel, David C; Morrongiello, Barbara A; Davis, Aaron L; Stewart, Julia; Bell, Melissa

    2012-04-01

    Pre-post-randomized design evaluated The Blue Dog, a dog safety software program. 76 children aged 3.5-6 years completed 3 tasks to evaluate dog safety pre- and postintervention: (a) pictures (recognition of safe/risky behavior), (b) dollhouse (recall of safe behavior via simulated dollhouse scenarios), and (c) live dog (actual behavior with unfamiliar live dog). Following preintervention evaluation, children were randomly assigned to dog or fire safety conditions, each involving 3 weeks of home computer software use. Children using Blue Dog had greater change in recognition of risky dog situations than children learning fire safety. No between-group differences emerged in recall (dollhouse) or engagement (live-dog) in risky behavior. Families enjoyed using the software. Blue Dog taught children knowledge about safe engagement with dogs, but did not influence recall or implementation of safe behaviors. Dog bites represent a significant pediatric injury concern and continued development of effective interventions is needed.

  6. Multiple infestation of Dioctophyme renale in dogs with leishmaniasis in Uruguaiana, RS - Report of five cases

    Directory of Open Access Journals (Sweden)

    Maria Lígia de Arruda Mistieri

    2014-06-01

    Full Text Available ABSTRACT. Mistieri M.L. de A., Pascon J.P. da E. & dos Santos F.P. [Multiple infestation of Dioctophyme renale in dogs with leishmaniasis in Uruguaiana, RS - Report of five cases.] Infestação múltipla de Dioctophyme renale em cães portadores de leishmaniose em Uruguaiana, RS - Relato de cinco casos. Revista Brasileira de Medicina Veterinária, 36(2:195-198, 2014. Universidade Federal do Pampa, BR 472, Km 592, Caixa Postal 118, Uruguaiana, RS 97500-970, Brasil. Email: mariamistieri@unipampa.edu.br Dioctophyme renale is a parasite of different animal species, including human beings. The parasite life cycle can be complex, involving intermediate hosts, definitive hosts and paratenic hosts, represented by different species of frog, rat and fish, specially. The domestic dogs are considered unusual and terminal hosts because they commonly present single parasite, enabling its reproduction and the cycle maintenance. This report presents a multiple infestation of D. renale (male and female specimens in five of nine dogs that underwent to euthanasia due to leishmaniasis. It was noticed two to eight parasites in each affected dog, summing 27 specimens, 12 males measuring between 9.0 and 21.5 cm in length and 15 females with 23.5 to 42.0 cm. In all dogs, the right kidney was completely destroyed. Actual epidemiological studies are necessary to check the real prevalence of the dioctophimosis in the region of Uruguaiana and the determination of the local parasite cycle. Deficient sanitary and hygiene conditions are commonly observed in the progression of D. renale and Leishmania sp. infections. It is possible that those conditions are the link between both disorders in the studied dogs.

  7. The role of serotoninergic neurons in rats agressive behaviour.

    Science.gov (United States)

    Czlonkowski, A; Kostowski, W; Markowska, L; Markiewicz, L; Wiśniewska, I

    1975-10-01

    Lesions of the dorsal and medial raphe nuclei that caused a marked decrease of the 5-HT level in the forebrain induced in groupped rats intraspecies aggressiveness but failed to increase mouse-killing behaviour. In rats isolated for 3 weeks lesions of the raphe nuclei did not change behaviour of "killers" and natural "non-killers". The role of 5-HT in mechanism of the aggressive behaviour is discussed.

  8. Quantified Dog: Supporting Dog Health through Persuasive Technologies

    OpenAIRE

    Hanell, Jenny

    2017-01-01

    In collaboration with HappyTail, a Swedish company developing a mobile application for dog owners, this qualitative research study examines and identifies important factors, for developers or other stakeholders, to have in mind when developing mobile applications that aim to support dog health. According to behavioural scientists, there needs to be a bridge between health themed mobile applications and behavioural change theories in order to achieve desirable results. Therefore, literature on...

  9. Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice

    International Nuclear Information System (INIS)

    Szabo, L.G.; Kelemen, E.

    1988-01-01

    Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production pf splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. (author)

  10. Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

    NARCIS (Netherlands)

    Javadi, S; Mol, JA; Boer, P; Boer, WH; Runberk, A

    2003-01-01

    The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were

  11. Jealousy in dogs.

    Science.gov (United States)

    Harris, Christine R; Prouvost, Caroline

    2014-01-01

    It is commonly assumed that jealousy is unique to humans, partially because of the complex cognitions often involved in this emotion. However, from a functional perspective, one might expect that an emotion that evolved to protect social bonds from interlopers might exist in other social species, particularly one as cognitively sophisticated as the dog. The current experiment adapted a paradigm from human infant studies to examine jealousy in domestic dogs. We found that dogs exhibited significantly more jealous behaviors (e.g., snapping, getting between the owner and object, pushing/touching the object/owner) when their owners displayed affectionate behaviors towards what appeared to be another dog as compared to nonsocial objects. These results lend support to the hypothesis that jealousy has some "primordial" form that exists in human infants and in at least one other social species besides humans.

  12. Evaluation of the Dogs, Physical Activity, and Walking (Dogs PAW) Intervention: A Randomized Controlled Trial.

    Science.gov (United States)

    Richards, Elizabeth A; Ogata, Niwako; Cheng, Ching-Wei

    2016-01-01

    To facilitate physical activity (PA) adoption and maintenance, promotion of innovative population-level strategies that focus on incorporating moderate-intensity lifestyle PAs are needed. The purpose of this randomized controlled trial was to evaluate the Dogs, Physical Activity, and Walking intervention, a 3-month, social cognitive theory (SCT), e-mail-based PA intervention. In a longitudinal, repeated-measures design, 49 dog owners were randomly assigned to a control (n = 25) or intervention group (n = 24). The intervention group received e-mail messages (twice weekly for 4 weeks and weekly for 8 weeks) designed to influence SCT constructs of self-efficacy, self-regulation, outcome expectations and expectancies, and social support. At baseline and every 3 months through 1 year, participants completed self-reported questionnaires of individual, interpersonal, and PA variables. Linear mixed models were used to assess for significant differences in weekly minutes of dog walking and theoretical constructs between groups (intervention and control) across time. To test self-efficacy as a mediator of social support for dog walking, tests for mediation were conducted using the bootstrapping technique. With the exception of Month 9, participants in the intervention group accumulated significantly more weekly minutes of dog walking than the control group. On average, the intervention group accumulated 58.4 more minutes (SD = 18.1) of weekly dog walking than the control group (p dog walking. Results indicate that a simple SCT-based e-mail intervention is effective in increasing and maintaining an increase in dog walking among dog owners at 12-month follow-up. In light of these findings, it may be advantageous to design dog walking interventions that focus on increasing self-efficacy for dog walking by fostering social support.

  13. Dog Owners' Interaction Styles: their Components and Associations with Reactions of Pet Dogs to a Social Threat

    Directory of Open Access Journals (Sweden)

    Giulia Cimarelli

    2016-12-01

    Full Text Available The bond dogs develop with their owner received increased attention in the last years but no study aimed at characterizing the way in which owners interact with their dogs in their daily life and how this might influence dog behavior. In order to examine how dog owners interact with their dogs, we first analyzed the behavior of 220 dog owners in 8 different standardized situations involving the owner-dog dyad. We extracted 3 behavioral factors related to Owner Warmth, Owner Social Support and Owner Control. Further, we investigated whether owner personality, gender and age are associated with these three factors. Results indicated that older owners scored lower in Owner Warmth and in Owner Social Support and higher in Owner Control than younger owners. Furthermore, owners scoring high in Owner Control scored lower in the personality trait Openness and owners scoring high in Owner Social Support scored lower in the personality trait Conscientiousness. Finally, we also analyzed whether the dogs´ reaction to an unfamiliar woman’s threatening approach was associated with the owners’ interaction styles. Results showed that dogs that searched for proximity of their owners during the threatening situation had owners scoring higher in Owner Warmth, as compared to dogs that reacted more autonomously, approaching the unfamiliar experimenter. Analogies between dog-owner interaction styles and human parenting styles are discussed considering the implications of the present findings for human social psychology as well as the practical relevance for dog welfare and human safety.

  14. Dog Owners' Interaction Styles: Their Components and Associations with Reactions of Pet Dogs to a Social Threat.

    Science.gov (United States)

    Cimarelli, Giulia; Turcsán, Borbála; Bánlaki, Zsófia; Range, Friederike; Virányi, Zsófia

    2016-01-01

    The bond dogs develop with their owner received increased attention in the last years but no study aimed at characterizing the way in which owners interact with their dogs in their daily life and how this might influence dog behavior. In order to examine how dog owners interact with their dogs, we first analyzed the behavior of 220 dog owners in 8 different standardized situations involving the owner-dog dyad. We extracted 3 behavioral factors related to " Owner Warmth ," " Owner Social Support ," and " Owner Control ." Further, we investigated whether owner personality, gender and age are associated with these three factors. Results indicated that older owners scored lower in " Owner Warmth " and in " Owner Social Support " and higher in " Owner Control " than younger owners. Furthermore, owners scoring high in " Owner Control " scored lower in the personality trait Openness and owners scoring high in " Owner Social Support " scored lower in the personality trait Conscientiousness. Finally, we also analyzed whether the dogs' reaction to an unfamiliar woman's threatening approach was associated with the owners' interaction styles. Results showed that dogs that searched for proximity of their owners during the threatening situation had owners scoring higher in " Owner Warmth ," as compared to dogs that reacted more autonomously, approaching the unfamiliar experimenter. Analogies between dog-owner interaction styles and human parenting styles are discussed considering the implications of the present findings for human social psychology as well as the practical relevance for dog welfare and human safety.

  15. [Comparison of fluoride concentrations in human, dog, fox and raccoon dog bones from northwestern Poland].

    Science.gov (United States)

    Palczewska-Komsa, Mirona

    2015-01-01

    Since the beginning of the XXth there has been a constant increase in fluoride (F-) emissions into the environment, mainly due to the development of industry, the fluoridation of drinking water, and the widespread use of toothpaste containing fluoride. All these factors have resulted in an intensive accumulation of F- in the bodies of vertebrates, mainly in their bones. It is therefore reasonable to estimate the F- concentration in humans and other long-lived mammals. Accordingly, ecotoxicologists worldwide have looked for mammalian species that may serve as good bioindicators of environmental fluoride pollution. In contrast to ungulates, long-lived domestic mammals and wild carnivores have rarely been used for this purpose (including the dog, fox and raccoon dog). The main aims of this study were to: 1) investigate F- concentrations in bones obtained from humans, dog, fox and raccoon dog from northwestern Poland, 2) perform intra- and inter-specific comparisons of F- concentrations in the studied mammalian bones against the background of environmental and living conditions, 3) examine the relationship between concentrations of F- in bones and the age or age category of the studied mammals. The study material comprised bones of the hip joint obtained from 36 patients who underwent hip replacement in Szczecin, 43 dogs from Szczecin veterinary clinics, 32 foxes and 18 raccoon dogs provided by hunters, with the whole test material consisting of 129 samples. The indications of F- (using potentiometry with Thermo Orion ion-selective electrodes) were performed in triplicate. The F- concentration was expressed on a dry weight basis. Interspecific analysis showed that the largest number of differences in the concentrations of F- were between the fox and raccoon, and then between the dog and fox, and then between the dog and the wild canids (foxes and raccoon dogs together). Close statistically significant differences were also found between the samples from humans and the

  16. How to Know whether a Dog is Dangerous: Myth, Superstition and its Influence on the Human-dog Relationship

    Directory of Open Access Journals (Sweden)

    Tanja Kovačič

    2015-04-01

    Full Text Available The relationship between humans and dogs is complex and ambivalent. The dog was the first animal that Homo sapiens domesticated. This means that the human-dog relationship has lasted longer than any other human-animal relationships. Despite all this, mythological, symbolic and folkloristic traditions often depict dogs in a negative light and as a dangerous and threatening force from the underworld. Due to the belief that seeing an unknown dog can lead to misfortune, accident or even death, people were often afraid of dogs. People had to invent certain rules that could help them determine which dog was dangerous and which was not. Those rules had to change over time based on the fact that human-dog relationship is culturally and historically defined. The author analyses stories from in the Glasovi (Voices collection to show that, in the last few centuries in the territory of modern Slovenia, black dogs where most feared by humans. In contrast, nowadays the most feared dogs are those of the Pit Bull and some other breeds. Nevertheless, the folk superstitions and prejudice toward black dogs is still present in modern Western societies. In the English language “black dog” symbolizes depression. And some are still reluctant to adopt large black dogs from the animal shelters.

  17. Estimation of pre-meiotic DNA synthesis period in the dog spermatozoa

    International Nuclear Information System (INIS)

    Ghosal, S.K.; Bandyopadhyay, T.; De, S.; Beauregard, L.J.

    1976-01-01

    About 10 μCi of 3 H-thymidine was injected into each of 4 arbitarary sites in each testis of 6 dogs. Biopsies were taken at 4-hour intervals coverning a period from 20.0 to 22.2 days post-injection. Kinetics of labelled spermatocytes was followed employing Kodak NTB-3 emulsion to conventionally prepared air-dried slides. The technique for calculating pre-meiosis DNA synthesis duration is same as that for estimating S period in mitotic cells. Current investigation suggests that the mean duration of pre-meiotic S period of Canine spermatocytes is 20.4 hrs as compared to 29 and 40 hrs in spermatocytes of mouse and golden hamster respectively. (author)

  18. Immunoglobulin G responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.

    Science.gov (United States)

    Bond, R; Lloyd, D H

    2002-04-20

    Serum immunoglobulin G (IgG) responses of healthy dogs and dogs with Malasseziapachydermatis dermatitis were compared by Western immunoblotting. M pachydermatis CBS 1879 was disrupted mechanically and its proteins were separated and blotted on to nitrocellulose membranes before being incubated with sera from eight healthy beagles, eight Irish setters with gluten-sensitive enteropathy, 15 healthy basset hounds, and 30 dogs with Mpachydermatis-associated dermatitis, 20 of which were basset hounds. The mean (se) numbers of bands of immunoreactivity observed in the seborrhoeic basset hounds (10.7 [0.4]) and affected mixed-breed dogs (9.4 [0.9]) were significantly greater than in the beagles (3-0 [1.0]), Irish setters (5.5 [1.1]) and healthy basset hounds (5.6 [0.7]). The number of bands identified was correlated (r(s) = 0.76, P dogs were immunoreactive towards the 132, 66 and 50 to 54 kDa proteins and the affected dogs were also usually reactive towards the 219, 110, 71 and 42 kDa proteins.

  19. Looking after chronically ill dogs

    DEFF Research Database (Denmark)

    Christiansen, Stine B.; Kristensen, Annemarie Thuri; Sandøe, Peter

    2013-01-01

    thus face similar challenges when caring for their animals. This qualitative study uncovers impacts on an owner's life, when attending to the care of an aged or chronically ill dog and reflects on the differing roles of caregivers with animal and human patients. Twelve dog owners were selected for in......-depth interviews based on the dogs' diagnoses, and the choice of treatments and care expected to affect the owner's life. Interviews were recorded, transcribed, and analyzed qualitatively. The dog owners reported several changes in their lives due to their dog's condition: practicalities like extra care, changes...... in use of the home, and restrictions relating to work, social life, and finances. These were time-consuming, tough, and annoying, but could often be dealt with through planning and prioritizing. Changes in the human–dog relationship and activities caused sadness and frustration, which in turn led...

  20. Who are the real bird brains? Qualitative differences in behavioral flexibility between dogs (Canis familiaris) and pigeons (Columba livia).

    Science.gov (United States)

    Laude, Jennifer R; Pattison, Kristina F; Rayburn-Reeves, Rebecca M; Michler, Daniel M; Zentall, Thomas R

    2016-01-01

    Pigeons given a simultaneous spatial discrimination reversal, in which a single reversal occurs at the midpoint of each session, consistently show anticipation prior to the reversal as well as perseveration after the reversal, suggesting that they use a less effective cue (time or trial number into the session) than what would be optimal to maximize reinforcement (local feedback from the most recent trials). In contrast, rats (Rattus norvegicus) and humans show near-optimal reversal learning on this task. To determine whether this is a general characteristic of mammals, in the present research, pigeons (Columba livia) and dogs (Canis familiaris) were tested with a simultaneous spatial discrimination mid-session reversal. Overall, dogs performed the task more poorly than pigeons. Interestingly, both pigeons and dogs employed what resembled a timing strategy. However, dogs showed greater perseverative errors, suggesting that they may have relatively poorer working memory and inhibitory control with this task. The greater efficiency shown by pigeons with this task suggests they are better able to time and use the feedback from their preceding choice as the basis of their future choice, highlighting what may be a qualitative difference between the species.

  1. Buster-Jangle Shot Dog

    International Nuclear Information System (INIS)

    Kaul, Dean C.

    1987-01-01

    Shot Dog of the Buster-Jangle Series used a device which had a high-explosive configuration virtually identical to that of the Nagasaki bomb, though with different fissionable components. Dog was detonated at a height of 431.9 m with the mean atmospheric conditions between burst and ground being dry air density 1.027 mg/cc and atmospheric moisture density 0.006 mg/cc. The ground was taken to be that of Nevada test site (NTS) area 9 with a water content of 8% by weight. The yield of the weapon was 21 kt. Results shown here for Buster-Jangle Shot Dog have been scaled from those calculated for Ranger Shot Fox. The design features and burst geometries of the two devices were deemed sufficiently similar to make this substitution in the absence of a radiation leakage spectrum calculated explicitly for Buster-Jangle Shot Dog. However, while the relative atmospheric contents of the two shots were very similar, Shot Fox took place in air of approximately 10% greater density than Shot Dog. Thus, scaled calculated results could not be obtained to compare with the three closest measurement points at Shot Dog

  2. Heterogeneity within the spleen colony-forming cell population in rat bone marrow

    International Nuclear Information System (INIS)

    Martens, A.C.; van Bekkum, D.W.; Hagenbeek, A.

    1986-01-01

    The pluripotent hemopoietic stem cell (HSC) of the rat can be enumerated in a spleen colony assay (SCA) in rats as well as mice. After injection of rat bone marrow into lethally irradiated mice, macroscopically visible spleen colonies (CFU-S) are found from day 6 through 14, but the number varies on consecutive days. In normal bone marrow a constant ratio of day-8 to day-12 colony numbers is observed. However, this ratio is changed after in vivo treatment of rats with cyclophosphamide, as well as after in vitro treatment of rat bone marrow with cyclophosphamide derivatives. This indicates that the CFU-S that form colonies on day 8 react differently to this treatment than the CFU-S that form colonies on day 12, and suggests heterogeneity among the CFU-S population. Posttreatment regrowth of day-8 and day-12 CFU-S is characterized by differences in population-doubling times (Td = 0.85 days vs 1.65 days). Another argument in support of the postulate of heterogeneity within the rat CFU-S population is derived from the fact that (in contrast to normal rat spleen) the spleen of leukemic rats contains high numbers of CFU-S that show a ratio of day-8 to day-12 CFU-S of 4.5, which is different than that observed for a CFU-S population in normal bone marrow (a ratio of 2.4). It is concluded that, in rat hemopoiesis, two populations of spleen colony-forming cells can be distinguished using the rat-to-mouse SCA. This indicates that mouse and rat hemopoiesis are comparable in this respect and that heterogeneity in the stem cell compartment is a general phenomenon

  3. Restriction fragment polymorphisms in the major histocompatibility complex of diabetic BB rats

    DEFF Research Database (Denmark)

    Kastern, W.; Dyrberg, T.; Scholler, J.

    1984-01-01

    DNA isolated from diabetic BB (BB/Hagedorn) rats was examined for restriction fragment length differences within the major histocompatibility complex (MHC) as compared with nondiabetic (W-subline) BB rats. Polymorphisms were detected using a mouse class I MHC gene as probe. Specifically, a 2-kb Bam......HI fragment was present in all the nondiabetic rats examined, but absent in the diabetic rats. Similar polymorphisms were observed with various other restriction enzymes, particularly XbaI, HindII, and SacI. There were no polymorphisms detected using either a human DR-alpha (class II antigen heavy chain...

  4. Some effects of sarcoptic mange on dogs.

    Science.gov (United States)

    Arlian, L G; Morgan, M S; Rapp, C M; Vyszenski-Moher, D L

    1995-10-01

    Sequential changes in pathology were examined for scabies-infested dogs to determine the effects of infestation with Sarcoptes scabiei var. canis. During 8 wk of infestation with S. scabiei, the progression of the disease was evaluated weekly by skin scrape, clinical examination, and blood analyses. At 8 wk, selected organs were microscopically examined for histopathology. All infested dogs developed an advanced level of scabies infestation by 8 wk. Of the 36 blood parameters evaluated, only values for erythrocyte sedimentation rate (ESR) deviated significantly from the normal ranges for dogs. However, infested dogs had significantly (P dogs. Red blood cell levels for infested dogs dropped significantly (P dogs compared to controls, some individual infested dogs exhibited eosinophilia at 4-8 wk of infestation. The ESRs for infested dogs were significantly (P dogs prior to infestation or control dogs. All parameters except neutrophils had returned to preinfestation levels by 2 wk after treatment for scabies. Neutrophil concentrations were no longer significantly different by 4 wk posttreatment. There were no significant differences in serum enzyme, biochemical and electrolyte concentrations between infested and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

    Science.gov (United States)

    Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

    2015-11-17

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

  6. Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

    Science.gov (United States)

    Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

    2003-01-01

    This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

  7. Contact with domestic dogs increases pathogen exposure in endangered African wild dogs (Lycaon pictus.

    Directory of Open Access Journals (Sweden)

    Rosie Woodroffe

    Full Text Available BACKGROUND: Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus. Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic "reservoir" hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. METHODOLOGY/PRINCIPAL FINDINGS: We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. CONCLUSIONS/SIGNIFICANCE: These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches--including no intervention--which are most appropriate for each pathogen.

  8. Contact with Domestic Dogs Increases Pathogen Exposure in Endangered African Wild Dogs (Lycaon pictus)

    Science.gov (United States)

    Woodroffe, Rosie; Prager, Katherine C.; Conrad, Patricia A.; Dubovi, Edward J.; Mazet, Jonna A. K.

    2012-01-01

    Background Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus). Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) “reservoir” hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. Methodology/Principal Findings We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. Conclusions/Significance These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches – including no intervention – which are most appropriate for each pathogen. PMID:22238695

  9. Does getting a dog increase recreational walking?

    Directory of Open Access Journals (Sweden)

    Knuiman Matthew W

    2008-03-01

    Full Text Available Abstract Background This study examines changes in socio-demographic, environmental and intrapersonal factors associated with dog acquisition in non-dog owners at baseline to 12-months follow-up and the effect of dog acquisition on minutes per week of recreational walking. Methods RESIDE study participants completed self-administered questionnaires (baseline and 12-months follow-up measuring physical activity, dog ownership, dog walking behavior as well as environmental, intrapersonal and socio-demographic factors. Analysis was restricted to 'Continuing non-owners' (i.e., non-owners at both baseline and follow-up; n = 681 and 'New dog owners' (i.e., non-owners who acquired a dog by follow-up; n = 92. Results Overall, 12% of baseline non-owners had acquired a dog at follow-up. Dog acquisition was associated with working and having children at home. Those who changed from single to couple marital status were also more likely to acquire a dog. The increase in minutes of walking for recreation within the neighborhood from baseline to follow-up was 48 minutes/week for new dog owners compared with 12 minutes/week for continuing non-owners (p p p > 0.05 after further adjustment for change in baseline to follow-up variables. Increase in intention to walk was the main factor contributing to attenuation of the effect of dog acquisition on recreational walking. Conclusion This study used a large representative sample of non-owners to examine the relationship between dog acquisition and recreational walking and provides evidence to suggest that dog acquisition leads to an increase in walking. The most likely mechanism through which dog acquisition facilitates increased physical activity is through behavioral intention via the dog's positive effect on owner's cognitive beliefs about walking, and through the provision of motivation and social support for walking. The results suggest that behavioral intention mediates the relationship between dog acquisition

  10. Juvenile cellulitis in dogs: 15 cases (1979-1988).

    Science.gov (United States)

    White, S D; Rosychuk, R A; Stewart, L J; Cape, L; Hughes, B J

    1989-12-01

    The records of 15 dogs diagnosed as having juvenile cellulitis (juvenile pyoderma, puppy strangles) were evaluated for clinical, laboratory, and therapeutic results. Mandibular lymphadenopathy was observed in 14 dogs, and was not associated with skin lesions in 5 dogs. Edema, pustules, papules, or crusts were noticed periorally, periocularly, on the chin or muzzle, or in the ears of those dogs with skin lesions. Eight dogs were lethargic; fever and anorexia were inconsistent findings. Four dogs had signs of pain on manipulation of their joints. Complete blood counts revealed leukocytosis with neutrophilia in 4 dogs, and normocytic, normochromic anemia in 6 dogs. Three dogs had suppurative lymphadenitis with many neutrophils. Cytology of the aspirate of pustules or abscesses in 6 dogs revealed many neutrophils without bacteria. Coagulase-positive Staphylococcus spp were isolated from draining lesions in 2 dogs. Intact abscesses and lymph nodes were negative for bacterial growth in 4 dogs. Three of these dogs were being administered antibiotics at the time of bacterial culturing. Cytology of the aspirates of joints in 3 of the 4 dogs with joint pain revealed suppurative arthritis with no bacteria, and the aspirates were negative for bacterial growth on culturing, although all 3 dogs were being administered antibiotics at the time of culturing. Of 12 dogs initially treated with antibiotics, only 4 (33%) responded favorably; the other 8 dogs were then given antibiotics and corticosteroids. Three dogs were initially given antibiotics and corticosteroids. All dogs treated concurrently with antibiotics and corticosteroids responded favorably. One of these dogs had a relapse after treatment was discontinued. The concurrent arthritis in 4 of the dogs resolved with treatment of the juvenile cellulitis and did not redevelop once the medication was discontinued. Concurrent treatment with antibiotics (cephalosporins) and prednisone (2.2 mg/kg of body weight/day) was the most

  11. Svetlana Suktueva, The Dog in Kalmyk Culture

    OpenAIRE

    Terbish, Baasanjav

    2015-01-01

    If a dog comes to your house, it is forbidden to chase it away or kill it. There is a belief that such dogs are the reincarnation of your ancestors. Such dogs should be fed and taken care of. The Kalmyks are superstitious about dogs. In Kalmykia there are three types of dog, (1) barg noha or watchdogs, (2) shurg noha or hounds, and (3) gavsh noha or mongrels. Watchdogs are considered to be helpers of herders. These dogs are also referred to as ‘dogs with 4 eyes’ (because they have spots abov...

  12. Service Dogs in the Perioperative Setting.

    Science.gov (United States)

    Levey, Janet A; Chappy, Sharon L

    2017-04-01

    Service dogs are critical for the independence of individuals with disabilities because they assist with daily living activities and help these individuals navigate society. Perioperative nurses need a working knowledge of disability laws pertaining to service dogs to provide patient-centered care for individuals using service dogs. This article provides information on the Americans With Disabilities Act regulations regarding service dogs, makes recommendations for the care of patients with service dogs across the perioperative continuum, and offers policy directives to ensure that safe, high-quality care is delivered to patients using service dogs. Copyright © 2017 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  13. I Walk My Dog Because It Makes Me Happy: A Qualitative Study to Understand Why Dogs Motivate Walking and Improved Health.

    Science.gov (United States)

    Westgarth, Carri; Christley, Robert M; Marvin, Garry; Perkins, Elizabeth

    2017-08-19

    Dog walking is a popular everyday physical activity. Dog owners are generally more active than non-owners, but some rarely walk with their dog. The strength of the dog-owner relationship is known to be correlated with dog walking, and this qualitative study investigates why. Twenty-six interviews were combined with autoethnography of dog walking experiences. Dog walking was constructed as "for the dog", however, owners represented their dog's needs in a way which aligned with their own. Central to the construction of need was perceptions of dog personality and behaviour. Owners reported deriving positive outcomes from dog walking, most notably, feelings of "happiness", but these were "contingent" on the perception that their dogs were enjoying the experience. Owner physical activity and social interaction were secondary bonuses but rarely motivating. Perceptions and beliefs of owners about dog walking were continually negotiated, depending on how the needs of the owner and dog were constructed at that time. Complex social interactions with the "significant other" of a pet can strongly motivate human health behaviour. Potential interventions to promote dog walking need to account for this complexity and the effect of the dog-owner relationship on owner mental wellbeing.

  14. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    OpenAIRE

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years 1–3 . This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years 4,5 . In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single inci...

  15. Behavioral and physiological reactions in dogs to a veterinary examination: Owner-dog interactions improve canine well-being.

    Science.gov (United States)

    Csoltova, Erika; Martineau, Michaël; Boissy, Alain; Gilbert, Caroline

    2017-08-01

    In order to improve well-being of dogs during veterinary visits, we aimed to investigate the effect of human social interactions on behavior and physiology during routine examination. Firstly, we assessed the impact of a standardized veterinary examination on behavioral and physiological indicators of stress in dogs. Secondly, we examined whether the owner's tactile and verbal interactions with the dog influenced behavioral and physiological stress-associated parameters. A randomized within-subjects crossover design was used to examine behavior (n=33), rectal temperature (n=33), heart rate (HR) (n=18), maximal ocular surface temperature (max OST) (n=13) and salivary cortisol concentrations (n=10) in healthy privately owned pet dogs. The study consisted of two experimental conditions: a) "contact" - owner petting and talking to the dog during the examination; b) "non-contact" - owner present during the examination but not allowed to interact with the dog. Our findings showed that the veterinary examinations produced acute stress responses in dogs during both "contact" and "non-contact" conditions, with significant increases in lip licking, HR, and max OST. A significant decrease in attempts to jump off the examination table (p=0.002) was observed during the examination in the "contact" compared to the "non-contact" condition. In addition, interactions of owners showed an attenuating effect on HR (p=0.018) and max OST (p=0.011) in their dogs. The testing order (first vs. second visit) had no impact on behavioral and physiological parameters, suggesting that dogs did not habituate or sensitize to the examination procedure. Moreover, the duration of the owner-dog interactions had no significant impact on the behavioral and physiological responses of their dogs. This study demonstrates that owner-dog interactions improve the well-being of dogs during a veterinary examination. Future research may assist in further understanding the mechanisms associated with reducing

  16. Radiation toxicity in dogs

    International Nuclear Information System (INIS)

    Norris, W.P.

    1975-01-01

    Progress is reported on studies of the effects of continuous (22 hr/day), whole-body γ-irradiation in the pure-bred beagle dog. Dogs were exposed continuously until death at one of four different exposure rates ranging from 5 to 35 R/day. The study is still 2441 days (approximately 6.7 yr) of irradiation. The experiment has narrowed to the dogs receiving 5 R/day and the controls. A group of dogs receiving one of these relatively low daily exposure rates may exhibit remarkably varied responses, both in survival times in the γ field and in ultimate causes of death. The basis for these large differences in responses of individual dogs remains mostly unexplained, but is presumed to reside in their genetic composition. The composite result in the study, however, demonstrates an orderly, step-wise appearance of clinical end points resulting from radiation-induced damage to the blood-forming tissues. About one-half the dogs exposed continuously to 10 R/day develop bone marrow aplasia and die of anemia, while the other one-half develop bone marrow hyperplasias and die of malignancies, usually myelogenous leukemias. In dogs exposed at rates greater than 10 R/day, aplastic bone marrows predominate; while hyperplastic responses are the dominant cause of death at 5 R/day. Only among the most recent deaths of dogs exposed continuously to either 10 or 5 R/day, have there appeared terminal causes of death unrelated to hematopoietic injury. These causes (degenerative and/or inflammatory disease and cancers of tissue other than bone marrow) suggest that we are now beginning to define the combinations of exposure rate and time of exposure that allow expressions of damage by tissues outside the hematopoietic system. (U.S.)

  17. Biochemical Characterisation of TSC1 and TSC2 Variants Identifiedd in Patients with Tuberous sclerosis Complex

    Science.gov (United States)

    2008-07-01

    different species (human, chimpanzee, macacca, cow, dog, horse, mouse, rat, chicken, pufferfish, honey bee , fruitfly, mosquito and fission yeast). The...by mutations in either the TSC1 or TSC2 tumour suppressor genes (2, 3). The TSC1 and TSC2 gene products form a protein complex that inhibits the...quantitative estimate of TSC1-TSC2 levels and S6K phosphorylation, the blots were scanned. 3. Phosphorylation of ribosomal protein S6 in Tsc1 -/- and

  18. CONTROLLING STREET DOG POPULATION IN MOSCOW

    OpenAIRE

    ZHULENKO A.S.; POLYNOVA G.V.

    2016-01-01

    The issue represents the analysis of the fundamentals and world-wide best practices of controlling street dog population in Moscow and other global cities. Actions proposed to improve the strategy of managing free-ranging dogs in Moscow.Some reasons of increase in number of stray dogs and “pet overpopulation” ware studied. There are ecological types of stray dogs characterized the types of running wild of dogs and foraging (food procurement) strategy of animals.The analysis of the basic princ...

  19. Tear ferning in normal dogs and dogs with keratoconjunctivitis sicca ...

    African Journals Online (AJOL)

    This study evaluates tear ferning as an ancillary technique for the evaluation of the canine tear film in normal eyes and eyes affected by keratoconjunctivitis sicca (KCS). Thirty dogs with KCS and 50 control dogs with normal tear film were evaluated with a full ophthalmoscopic examination and a Schirmer tear test type 1 ...

  20. Detection of Hepatozoon canis in the Brown Dog Tick and Domestic Dogs in Peninsular Malaysia.

    Science.gov (United States)

    Prakash, Batah Kunalan; Low, Van Lun; Tan, Tiong Kai; Vinnie-Siow, Wei Yin; Lim, Yvonne Ai-Lian; Morvarid, Akhavan Rezaei; Azman, Adzzie Shazleen; Yeong, Yze Shiuan; AbuBakar, Sazaly; Sofian-Azirun, Mohd

    2018-05-17

    Hepatozoon canis has been widely reported in dogs. Its prevalence in ticks, however, has not been well-established. Here we determine the occurrence of Hepatozoon DNA in the brown dog tick Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) sensu lato (s.l.) and domestic dogs from Peninsular Malaysia using a polymerase chain reaction (PCR) assay based on amplification of the 18S ribosomal RNA coding sequence. Our results revealed a relatively low prevalence of H. canis DNA in both R. sanguineus s.l. (0.7%) and dogs (3.33%). This study represents the first report of H. canis DNA in R. sanguineus s.l. in Malaysia, highlighting the risk of this infection in dogs.

  1. Management of tick infestation in dogs

    Directory of Open Access Journals (Sweden)

    Somasani Ayodhya

    2014-09-01

    Full Text Available The present study was carried out during the month of January 2014 when a total of 148 dogs with history of various diseases were presented to the Campus Veterinary Hospital, Teaching Veterinary Clinical Complex, College of Veterinary Science, Rajendranagar, Hyderabad, India. Out of 148 dogs that were presented to the hospital, 48 dogs had the clinical signs of loss of hair, itching, and reduced food intake. The dogs were restless and continuously rubbed their bodies against the walls in the houses, and scratching with their legs. Clinical examination of the dogs revealed presence of alopecia, pruritus, and the formation of small crusts. All 48 dogs were treated with ivermectin by subcutaneous injection dosed at 0.02 mL/kg body weight at a weekly interval for 2 to 3 weeks. All dogs were bathed with cypermethrin shampoo weekly once for 2-3 weeks. In the present study, it was observed that ivermectin/cypermethrin combination therapy was effective for the management of tick infestation in dogs.

  2. Mandatory desexing of dogs: one step in the right direction to reduce the risk of dog bite? A systematic review.

    Science.gov (United States)

    D'Onise, Katina; Hazel, Susan; Caraguel, Charles

    2017-06-01

    Preventing dog bites is an intractable problem given the complex dog bite injury environment. Desexing of dogs has the opportunity of creating a safer injury environment, given the potential links between desexing and behaviour change in dogs. A systematic review of the literature was conducted to examine the evidence for desexing of dogs to reduce dog bite risk within a population health paradigm. Medline and CAB Abstracts were searched for studies that reported data on the association of dog neuter status with the risk of dog bite. All definitions of dog bite were included and all empirical studies were included in the review, limited to those published in English. Quality appraisal and data extraction were based on the 2013 evidence-based practice and critical appraisal tool from the University of Auckland. Five out of six observational studies, from four study populations found evidence that intact dogs were associated with an increased risk of dog bite compared with desexed dogs. The effect sizes ranged across the studies and given the heterogeneity of the studies no single effect size on the association between desexing and dog bite risk could be estimated. There is consistent evidence that desexing dogs is associated with a reduced risk of dog bite, although the studies reflect association and may not be causal. Although recent publications have suggested desexing is associated with health and behavioural costs in some breeds, population level evidence supports desexed dogs having a longer lifespan, and being less likely to wander with the added benefit of reducing unwanted litters. Thus, mandatory desexing presents a possible opportunity for prevention of dog bites expanding dog bite prevention beyond an education-only approach. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Genomic sequences of murine gamma B- and gamma C-crystallin-encoding genes: promoter analysis and complete evolutionary pattern of mouse, rat and human gamma-crystallins.

    Science.gov (United States)

    Graw, J; Liebstein, A; Pietrowski, D; Schmitt-John, T; Werner, T

    1993-12-22

    The murine genes, gamma B-cry and gamma C-cry, encoding the gamma B- and gamma C-crystallins, were isolated from a genomic DNA library. The complete nucleotide (nt) sequences of both genes were determined from 661 and 711 bp, respectively, upstream from the first exon to the corresponding polyadenylation sites, comprising more than 2650 and 2890 bp, respectively. The new sequences were compared to the partial cDNA sequences available for the murine gamma B-cry and gamma C-cry, as well as to the corresponding genomic sequences from rat and man, at both the nt and predicted amino acid (aa) sequence levels. In the gamma B-cry promoter region, a canonical CCAAT-box, a TATA-box, putative NF-I and C/EBP sites were detected. An R-repeat is inserted 366 bp upstream from the transcription start point. In contrast, the gamma C-cry promoter does not contain a CCAAT-box, but some other putative binding sites for transcription factors (AP-2, UBP-1, LBP-1) were located by computer analysis. The promoter regions of all six gamma-cry from mouse, rat and human, except human psi gamma F-cry, were analyzed for common sequence elements. A complex sequence element of about 70-80 bp was found in the proximal promoter, which contains a gamma-cry-specific and almost invariant sequence (crygpel) of 14 nt, and ends with the also invariant TATA-box. Within the complex sequence element, a minimum of three further features specific for the gamma A-, gamma B- and gamma D/E/F-cry genes can be defined, at least two of which were recently shown to be functional. In addition to these four sequence elements, a subtype-specific structure of inverted repeats with different-sized spacers can be deduced from the multiple sequence alignment. A phylogenetic analysis based on the promoter region, as well as the complete exon 3 of all gamma-cry from mouse, rat and man, suggests separation of only five gamma-cry subtypes (gamma A-, gamma B-, gamma C-, gamma D- and gamma E/F-cry) prior to species separation.

  4. Identification and target prediction of miRNAs specifically expressed in rat neural tissue

    Directory of Open Access Journals (Sweden)

    Tu Kang

    2009-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

  5. Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.E.; Burns, F.J.; Altshuler, B.

    1978-02-01

    The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

  6. Assessment of tear film osmolarity using the TearLab™ osmometer in normal dogs and dogs with keratoconjunctivitis sicca.

    Science.gov (United States)

    Sebbag, Lionel; Park, Shin Ae; Kass, Philip H; Maggs, David J; Attar, Mayssa; Murphy, Christopher J

    2017-07-01

    To evaluate repeatability and reproducibility of tear osmolarity measured using the TearLab ™ osmometer in normal dogs and to assess its diagnostic potential in dogs with keratoconjunctivitis sicca (KCS). Beagle dogs; six normal and five with KCS. Tear osmolarity and Schirmer tear test-1 (STT-1) values were obtained at various times. Normal dogs were assessed for diurnal variation and repeatability and reproducibility of measurements. Dogs with KCS were evaluated before and after 5 months' topical twice-daily therapy with 2% cyclosporine. Mean ± SD tear osmolarity (mOsm/L) was significantly higher in normal dogs (337.4 ± 16.2) than in dogs with KCS before therapy (306.2 ± 18.0; P dogs, tear osmolarity readings were stable during the daytime (P = 0.99). Repeated measurements revealed high variability and typically poor-to-moderate repeatability and reproducibility, although this was improved by taking three successive measurements at each session. Considering combined data from all dogs, a positive correlation existed between STT-1 and tear osmolarity measurements (Pearson's correlation test, P = 0.04, r = 0.62). Canine tear osmolarity as determined by TearLab ™ osmometer was variable, required multiple readings to be informative, and differed from values reported for humans. Dogs with KCS had a lower tear osmolarity than did normal dogs, and this increased following cyclosporine therapy. © 2016 American College of Veterinary Ophthalmologists.

  7. Purification and characterization of a small dermatan sulphate proteoglycan implicated in the dilatation of the rat uterine cervix.

    Science.gov (United States)

    Kokenyesi, R; Woessner, J F

    1989-06-01

    A small dermatan sulphate proteoglycan (DSPG) was extracted from rat cervices and was purified by using DEAE-Sephacel ion-exchange chromatography, gel filtration on Sepharose CL-2B and CsCl-density-gradient centrifugation. Sedimentation-equilibrium centrifugation gave a weight-average Mr of 95,000. Amino acid analysis showed a high content of aspartic acid, glutamic acid, glycine and leucine. The glycosaminoglycan chains had Mr 50,000 as determined by gel filtration. Chondroitin AC lyase and chondroitin ABC lyase digestions of these chains showed that they were composed of 75% dermatan sulphate and 25% chondroitin sulphate. Chondroitin ABC lyase digestion produced a core protein of Mr 45,000. The core protein, after treatment with HF, had Mr 37,000. Amino acid sequences of the N-terminus and a CNBr-cleavage peptide showed similarity to the sequences of core proteins of small proteoglycans of bovine and human origin, but the N-terminal glycosaminoglycan-attachment site (Ser-Gly-Ile-Ile) differed from the consensus sequence (Ser-Gly-Xaa-Gly) [Bourdon, Krusius, Campbell, Schwartz & Ruoslahti (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 3194-3198]. A polyclonal antibody against the rat cervical DSPG reacted with small proteoglycans from cervices of human, mouse, dog, cow and sheep. DSPG is the major proteoglycan species present in the cervix. The amount of DSPG per cervix increases 4-fold during pregnancy, then falls precipitously within 1 day post partum. A role in cervical dilatation is postulated for this proteoglycan.

  8. Pulmonary mineralization in four dogs with Cushing's syndrome

    International Nuclear Information System (INIS)

    Berry, C.R.; Ackerman, N.; Monce, K.

    1994-01-01

    The clinical and imaging features of four dogs with Cushing's syndrome and pulmonary mineralization are reviewed. Three dogs presented with a primary complaint of respiratory distress/dyspnea. Three dogs had pituitary dependent Cushing's syndrome, while the remaining one dog had iatrogenic Cushing's syndrome. Each dog had clinical features typical for Cushing's syndrome. Two of the dogs were euthanized due to progressive hypoxemia. In each dog, the serum calcium, phosphorous, blood urea nitrogen and creatinine were normal. A generalized increase in unstructured interstitial pulmonary opacity with diffuse mineralization was noted on thoracic radiographs of all dogs. In one dog, an ill-defined nodular interstitial pattern of mineralization was present. Delayed bone phase scintigraphy using 99m Technetium methylene diphosphonate documented generalized pulmonary uptake in two dogs. 99m Technetium labeled microaggregated albumin lung perfusion scans were normal in these two dogs. 99m Tc-MDP scintigraphy can provide useful information in diagnosing pulmonary mineralization in Cushingoid dogs

  9. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.

    2007-01-01

    Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...... applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs....

  10. Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

    Science.gov (United States)

    Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

    2014-07-01

    International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment. © 2014 by The Author(s).

  11. 9 CFR 3.8 - Exercise for dogs.

    Science.gov (United States)

    2010-01-01

    ... Cats 1 Animal Health and Husbandry Standards § 3.8 Exercise for dogs. Dealers, exhibitors, and research... dog(s); or (3) Any dog exhibits aggressive or vicious behavior. (c) Methods and period of providing...

  12. Assistance Dogs: Historic Patterns and Roles of Dogs Placed by ADI or IGDF Accredited Facilities and by Non-Accredited U.S. Facilities.

    Science.gov (United States)

    Walther, Sandra; Yamamoto, Mariko; Thigpen, Abigail Paige; Garcia, Anaissa; Willits, Neil H; Hart, Lynette A

    2017-01-01

    Dogs' roles to support people with disabilities are increasing. Existing U.S. laws and regulations pertaining to the use of dogs for people with disabilities are only minimally enforced. Pushback legislation against some aspects of uses of assistance dogs currently is being passed or proposed in several states. Further, the U.S. Department of the Army and the Veterans' Administration support only dogs trained by an Assistance Dogs International (ADI) or International Guide Dog Federation (IGDF) accredited facility. Lacking a mandatory national process for screening the selection, training, and placement of assistance dogs with persons who have disabilities, the U.S. offers a creative but confusing opportunity for people to train their own dogs for any disability. While no U.S. surveillance system monitors assistance dogs, other countries generally have a legislated or regulatory process for approving assistance dogs or a cultural convention for obtaining dogs from accredited facilities. We conducted an online survey investigating current demographics of assistance dogs placed in 2013 and 2014 with persons who have disabilities, by facilities worldwide that are associated with ADI or IGDF and by some non-accredited U.S. facilities. Placement data from ADI and IGDF facilities revealed that in most countries aside from the U.S., guide dogs were by far the main type of assistance dog placed. In the U.S., there were about equal numbers of mobility and guide dogs placed, including many placed by large older facilities, along with smaller numbers of other types of assistance dogs. In non-accredited U.S. facilities, psychiatric dogs accounted for most placements. Dogs for families with an autistic child were increasing in all regions around the world. Of dog breeds placed, accredited facilities usually mentioned Labrador Retrievers and Golden Retrievers, and sometimes, German Shepherd Dogs. The facilities bred their dogs in-house, or acquired them from certain breeders

  13. The response of guide dogs and pet dogs (Canis familiaris) to cues of human referential communication (pointing and gaze).

    Science.gov (United States)

    Ittyerah, Miriam; Gaunet, Florence

    2009-03-01

    The study raises the question of whether guide dogs and pet dogs are expected to differ in response to cues of referential communication given by their owners; especially since guide dogs grow up among sighted humans, and while living with their blind owners, they still have interactions with several sighted people. Guide dogs and pet dogs were required to respond to point, point and gaze, gaze and control cues of referential communication given by their owners. Results indicate that the two groups of dogs do not differ from each other, revealing that the visual status of the owner is not a factor in the use of cues of referential communication. Both groups of dogs have higher frequencies of performance and faster latencies for the point and the point and gaze cues as compared to gaze cue only. However, responses to control cues are below chance performance for the guide dogs, whereas the pet dogs perform at chance. The below chance performance of the guide dogs may be explained by a tendency among them to go and stand by the owner. The study indicates that both groups of dogs respond similarly in normal daily dyadic interaction with their owners and the lower comprehension of the human gaze may be a less salient cue among dogs in comparison to the pointing gesture.

  14. Pharmacokinetics and enhanced bioavailability of candidate cancer preventative agent, SR13668 in dogs and monkeys.

    Science.gov (United States)

    Kapetanovic, Izet M; Muzzio, Miguel; Hu, Shu-Chieh; Crowell, James A; Rajewski, Roger A; Haslam, John L; Jong, Ling; McCormick, David L

    2010-05-01

    SR13668 (2,10-dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole), is a new candidate cancer chemopreventive agent under development. It was designed using computational modeling based on a naturally occurring indole-3-carbinol and its in vivo condensation products. It showed promising anti-cancer activity and its preclinical toxicology profile (genotoxicity battery and subchronic rat and dog studies) was unremarkable. However, it exhibited a very poor oral bioavailability (Solutol, were tested in dogs and monkeys. Levels of SR13668 were measured in plasma and blood using a high-performance liquid chromatograph-tandem mass spectrometer system. Non-compartmental analysis was used to derive pharmacokinetic parameters including the bioavailability. The Solutol formulation yielded better bioavailability reaching a maximum of about 14.6 and 7.3% in dogs and monkeys, respectively, following nominal oral dose of ca. 90 mg SR13668/m(2). Blood levels of SR13668 were consistently about threefold higher than those in plasma in both species. SR13668 did not cause untoward hematology, clinical chemistry, or coagulation effects in dogs or monkeys with the exception of a modest, reversible increase in liver function enzymes in monkeys. The lipid-based surfactant/emulsifiers, especially Solutol, markedly enhanced the oral bioavailability of SR13668 over that previously seen in preclinical studies. These formulations are being evaluated in a Phase 0 clinical study prior to further clinical development of this drug.

  15. Rats, cats, and elephants, but still no unicorn: induced pluripotent stem cells from new species.

    Science.gov (United States)

    Trounson, Alan

    2009-01-09

    Two independent studies in this issue of Cell Stem Cell (Liao et al., 2009; Li et al., 2009) derive rat induced pluripotent stem cells (iPSCs). In one report, the method used results in rat and human iPSCs that exhibit phenotypic traits similar to mouse embryonic stem cells.

  16. Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

    DEFF Research Database (Denmark)

    Rune, Ida; Rolin, Bidda; Lykkesfeldt, Jens

    2018-01-01

    In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control...

  17. Effects of exogenous hormones on spermatogenesis in the male prairie dog (Cynomys ludovicianus).

    Science.gov (United States)

    Foreman, D

    1998-01-01

    Male prairie dogs (Cynomys ludovicianus) breed anually and have complete testicular regression. Changes in the seminiferous tubules during the annual cycle have been described recently (Foreman, 1997). This is the first description of spermatogenesis in such a species. The definition of tubular stages during the cycle allows for evaluation of the effects of exogenous hormones, hemicastration, and hemicryptorchidism on spermatogenesis during the annual cycle. Hemicastration was performed during stages of the annual cycle to determine effects of exogenous hormones on remaining testes. Hemicryptorchidism was also done during stages of the annual cycle. FSH, LH, and testosterone were given in high and low doses for short- or long-term treatment periods during stages of the annual cycle. Testicular weights and counts of cell types in tubules of control and treated testes were made on testis tissues. Hemicastration during the out-of-season period does not cause compensatory hypertrophy of the remaining testis, but during recrudescence, hypertrophy of the remaining testis occurs. Hemicastration does not prevent loss of weight by the remaining testis during regression. The seminiferous epithelium of hemicryptorchid prairie dog testes shows damage during spermatogenic activity but not during testicular inactivity. Similarly, hemicryptorchid 15-day-old rat testes do not show damage from hemicryptorchidism. Long-term treatment with FSH preparations during testicular inactivity increased testis weights, spermatogonial proliferation, and spermatocyte differentiation in conjunction with Sertoli cell differentiation. Short-term treatments with low doses increased spermatogonial proliferation and abnormal meiotic activity. Both long- and short-term treatments with LH caused increased sloughing of germ cells and stimulated Leydig and Sertoli cells. Testosterone propionate injections stimulated Sertoli secretions but not Leydig cell activity. Hemicastration during inactivity does

  18. Human behavior preceding dog bites to the face.

    Science.gov (United States)

    Rezac, P; Rezac, K; Slama, P

    2015-12-01

    Facial injuries caused by dog bites pose a serious problem. The aims of this study were to determine human behavior immediately preceding a dog bite to the face and to assess the effects of victim age and gender and dog sex and size on the location of the bite to the face and the need for medical treatment. Complete data on 132 incidents of bites to the face were analysed. A human bending over a dog, putting the face close to the dog's face, and gazing between victim and dog closely preceded a dog bite to the face in 76%, 19% and 5% of cases, respectively. More than half of the bites were directed towards the central area of the victim's face (nose, lips). More than two thirds of the victims were children, none of the victims was an adult dog owner and only adult dogs bit the face. Victim's age and gender and dog's sex and size did not affect the location of the bite on the face. People who were bitten by large dogs sought medical treatment more often than people who were bitten by small dogs (P face close to the dog's face and gazing between human and dog should be avoided, and children should be carefully and constantly supervised when in the presence of dogs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Lead intoxication in dogs: risk assessment of feeding dogs trimmings of lead-shot game.

    Science.gov (United States)

    Høgåsen, Helga R; Ørnsrud, Robin; Knutsen, Helle K; Bernhoft, Aksel

    2016-07-25

    Expanding lead-based bullets, commonly used for hunting of big game, produce a scattering of lead particles in the carcass around the wound channel. Trimmings around this channel, which are sometimes fed to dogs, may contain lead particles. The aim of this study was to assess potential health effects of feeding dogs such trimmings. Lead ingestion most commonly causes gastrointestinal and neurological clinical signs, although renal, skeletal, haematological, cardiovascular and biochemical effects have also been reported. Experimental data indicate that a daily dose of around 1 mg lead as lead acetate/kg body weight for ten days may be considered as a Lowest Observed Effect Level in dogs. Acute toxicity documentation from the Centers for Disease Control and Prevention indicates 300 mg/kg body weight as the lowest dose of lead acetate causing death in dogs after oral ingestion. Our assessment suggests that dogs fed trimmings of lead-shot game may be affected by the amounts of lead present, and that even deadly exposure could occasionally occur. The intestinal absorption of lead from bullets was assumed to be 10-80 % of that of lead acetate, reflecting both the variability in particle size and uncertainty about the bioavailability of metallic lead in dogs. Despite data gaps, this study indicates that feeding dogs trimmings of lead-shot game may represent a risk of lead intoxication. More research is needed to assess the exact consequences, if lead-based bullets are still to be used. Meanwhile, we recommend that trimmings close to the wound channel should be made inaccessible to dogs, as well as to other domestic or wild animals.

  20. A CNGB1 frameshift mutation in Papillon and Phalene dogs with progressive retinal atrophy.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA or degeneration resembles human retinitis pigmentosa (RP and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10(-8 with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes.

  1. Protection of dogs against canine heartworm infection 28 days after four monthly treatments with Advantage Multi® for Dogs.

    Science.gov (United States)

    Bowman, Dwight D; Grazette, Alyssa R; Basel, Chris; Wang, Yingying; Hostetler, Joseph A

    2016-01-08

    Monthly heartworm preventives are designed to protect dogs by killing heartworms acquired the month prior to their administration, and after treatment with most products, the drug levels rapidly dissipate to very low levels. Work with Advantage Multi® for Dogs (imidacloprid + moxidectin) topical solution showed protection against hookworm infection throughout the month after administration of several monthly doses suggesting that similar protection might occur with heartworms. This study assessed the amount of protection afforded to dogs by the administration of four monthly doses of Advantage Multi for Dogs prior to infection with third-stage heartworm larvae (Dirofilaria immitis) 28 days after the last (fourth) treatment. There were 16 purpose-bred mongrel dogs in the study that were divided into two groups, 8 control and 8 treated dogs. Dogs were housed in a manner preventing contact between animals and groups, and personal protective gear worn by staff minimised the chance spread of the topically applied product between runs. The dogs in the treated group received monthly applications of Advantage Multi for Dogs as per label instructions on Study Days 0, 28, 56, and 84. On Study Day 112, all 16 dogs received 50 third-stage larvae of D. immitis ("Missouri" isolate) via subcutaneous inoculation in the inguinal region. The study was terminated on Day 264, and the number of heartworms per dog was determined at necropsy. Moxidectin levels after 4 treatments 28 days apart were near steady state on Study Day 112 when the dogs were inoculated with D. immitis third-stage larvae. At necropsy, 152 days after infection, all the control dogs had adult worms in their pulmonary arteries (geometric mean = 33.9; range 25-41), and none of the dogs treated four times prior to infection, with the last treatment 30 days prior to infection, harbored worms at necropsy. The efficacy of prevention was 100% when the dogs were infected 28 days after the last monthly treatment

  2. A qualitative investigation of the perceptions of female dog-bite victims and implications for the prevention of dog bites.

    Science.gov (United States)

    Westgarth, Carri; Watkins, Francine

    2015-01-01

    Preventing dog bites is an increasingly important public health and political issue with implications for both human and animal health and welfare. Expert opinion is that most bites are preventable. Intervention materials have been designed to educate people on how to assess the body language of dogs, evaluate risk, and take appropriate action. The effectiveness of this approach is rarely evaluated and the incidence of dog bites is thought to be increasing. Is the traditional approach to dog bite prevention working as well as it should? In this novel, small scale qualitative study, the perceptions of victims regarding their dog bite experience were explored in-depth. The study recruited 8 female participants who had been bitten by a dog in the past 5 years. In-depth, one-to-one interviews were conducted, transcribed, and analyzed using thematic analysis. The findings indicate that dog bites may not be as easily preventable as previously presumed, and that education about dog body language may not prevent some types of dog bites. The reasons participants were bitten were multifaceted and complex. In some cases, there was no interaction with the dog before the bite so there was no opportunity to assess the situation and modify behavior around the dog accordingly. Identifying who was to blame, and had responsibility for preventing the bite, was straightforward for the participants in hindsight. Those bitten blamed themselves and/or the dog owner, but not the dog. Most participants already felt they had a theoretical knowledge that would allow them to recognize dog aggression before the dog bite, yet participants, especially those who worked regularly with dogs, routinely believed, "it would not happen to me." We also identified an attitude that bites were "just one of those things," which could also be a barrier prevention initiatives. Rather than being special to the human-canine relationship, the attitudes discovered mirror those found in other areas of injury

  3. Bone tumors in R30 dogs

    International Nuclear Information System (INIS)

    Morgan, J.P.; Pool, R.R.

    1980-01-01

    Radiographic and histologic findings from a mid-level group (38 dogs) of radium toxicity dogs showed 49 primary bone tumors with a high frequency of tumors within the axial skeleton. Additional primary bone tumors, bone tumors metastatic to bone, soft tissue metastases, and lung metastases were detected. No bone tumors were identified in 3 dogs. Lesions described as radiation osteodystrophy were found in all but 2 dogs

  4. Seroprevalence of Leptospirosis in Working Dogs.

    Science.gov (United States)

    Lau, S F; Wong, J Y; Khor, K H; Roslan, M A; Abdul Rahman, M S; Bejo, S K; Radzi, R; Bahaman, A R

    2017-12-01

    Working dogs are canine animals that have been trained to assist human beings in carrying out various tasks. They help in guarding property, performing rescues, assisting the visually impaired or physically handicapped, searching for drugs, explosives, and others. Leptospirosis is one of the most widespread zoonotic diseases in the world and a commonly occurring disease of the tropics and subtropics. In Malaysia, all working dogs are normally vaccinated with serovars, Pomona, Icterohaemorrhagiae, Canicola, and Grippotyphosa based on protocols recommended from other countries. The duration of immunity in vaccinated dogs for Leptospira can last up to 13 months; however, there is no full crossprotection between the different serovars. Five representative canine units from different government agencies in Malaysia (n = 96 dogs) were recruited in this study. For detection, the microscopic agglutination test was performed by incubating the serum from dogs with various serovars of leptospires, namely, Icterohaemorrhagiae, Canicola, Pomona, Grippotyphosa, Australis, Bataviae, Javanica, Tarassovi, Hebdomadis, Lai, and Pyrogenes. The plasma obtained was used for polymerase chain reaction (PCR) analysis, for the detection of 16S rRNA, and lipL 32 genes of Leptospira. Out of the 96 dogs sampled, only 3 dogs were positive toward serovars, Australis, Bataviae, and Javanica, based on the cutoff point at 1:80. The seroprevalence of canine leptospirosis in this population was 3.1% (n = 3/96). However, all 96 blood samples of working dogs tested negative for both pathogenic and nonpathogenic Leptospira genes. The results revealed that, by vaccination alone, working dogs were not fully protected against leptospirosis and could pose a risk to dog handlers. A preventative and control protocol for leptospirosis is warranted, and its implementation should be monitored and improved accordingly from time to time, in order to maintain a healthy condition in both working dogs and their

  5. Self-disclosure with dogs

    OpenAIRE

    Evans-Wilday, Aislinn

    2016-01-01

    There exists an abundance of literature on the health benefits of dog-ownership and the health benefits of self-disclosure however, there has been no research into the potential health benefits of self-disclosure to dogs. This thesis addresses that gap in the literature. Among the literature on the health benefits of dog-ownership there is often a focus on the benefits to people with clinical conditions or living in care facilities – much less investigated are the benefits to ‘normally-fun...

  6. Anaesthesia, not number of sessions, influences the magnitude and duration of an aHF-rTMS in dogs.

    Directory of Open Access Journals (Sweden)

    Robrecht Dockx

    Full Text Available Currently, the rat has been a useful animal model in brain stimulation research. Nevertheless, extrapolating results from rodent repetitive Transcranial Magnetic Stimulation (rTMS research to humans contains several hurdles. This suggests the desperate need for a large animal model in translational rTMS research. The dog would be a valid choice, not only due to the fact that humans and dogs share a neurophysiological background, but a similar neuropathological background as well.In order to evaluate the feasibility of the canine rTMS animal model, this study aimed to evaluate the neurophysiological response in dogs on a, clinically used, accelerated high frequency (aHF rTMS protocol. This aHF-rTMS (20 Hz protocol was performed under anaesthesia or sedation and either 20 sessions or 5 sessions were given to each dog.21 healthy dogs were randomly subjected to one of the four aHF-rTMS protocols (1 sham and 3 active protocols. For each dog, the perfusion indices (PI, of a [99mTc]HMPAO scan at 4 time points, for the left frontal cortex (stimulation target were calculated for each protocol.Concerning sham stimulation, the average PI remained at the baseline level. The main result was the presence of a direct transitory increase in rCBF at the stimulation site, both under anaesthesia and sedation. Nevertheless the measured increase in rCBF was higher but shorter duration under sedation. The magnitude of this increase was not influenced by number of sessions. No changes in rCBF were found in remote brain regions.This study shows that, despite the influence of anaesthesia and sedation, comparable and clinically relevant effects on the rCBF can be obtained in dogs. Since less methodological hurdles have to be overcome and comparable results can be obtained, it would be acceptable to put the dog forward as an alternative translational rTMS animal model.

  7. Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Sommer, Yasmin; Glatt, Hansruedi; Seidel, Albrecht; Monien, Bernhard H

    2016-01-01

    5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent rodent carcinogens that are present in thermally processed foodstuffs. The carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)-mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous SULT forms substantially differ in substrate specificity and tissue distribution. This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and rats. The catalytic efficiencies (k cat/K M) of HMF sulfoconjugation of human SULT1A1 (13.7 s(-1) M(-1)), mouse Sult1a1 (15.8 s(-1) M(-1)) and 1d1 (4.8 s(-1) M(-1)) and rat Sult1a1 (5.3 s(-1) M(-1)) were considerably higher than those of all other SULT forms investigated (≤0.73 s(-1 )M(-1)). FFA sulfoconjugation was monitored using adenosine as a nucleophilic scavenger for the reactive 2-sulfoxymethylfuran (t 1/2 = 20 s at 37 °C). The resulting adduct N (6)-((furan-2-yl)methyl)-adenosine (N (6)-MF-A) was quantified by isotope-dilution UPLC-MS/MS. The rates of N (6)-MF-A formation showed that hSULT1A1 and its orthologues in mice and rats were also the most important contributors to FFA sulfoconjugation in each of the species. Taken together, the catalytic capacity of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which carcinogenic effects of HMF and FFA were detected. This is of primary concern due to the expression of hSULT1A1 in many different tissues.

  8. Recognizing the value of assistance dogs in society.

    Science.gov (United States)

    Audrestch, Hilary M; Whelan, Chantelle T; Grice, David; Asher, Lucy; England, Gary C W; Freeman, Sarah L

    2015-10-01

    Assistance dogs are specially trained to undertake a variety of tasks to help individuals with disabilities. This review gives an overview of the different types of assistance dogs in the UK, including guide dogs, hearing dogs, mobility assistance dogs, service dogs and dual-purpose dogs. The literature describes many benefits of assistance dogs, including their impact on physical wellbeing and safety of their 'owners,' as well as on psychological wellbeing and social inclusion. The role of assistance dogs in society is widely recognized by the public, but is not currently acknowledged in government social policy. The current evidence on the benefits of assistance dogs is limited by the type and scale of current research. This article highlights the need for independent funding for high quality research to enable social care and policy makers to make evidence-based decisions on the value of assistance dogs to people with disabilities. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Human–dog interactions and behavioural responses ofvillage dogs in coastal villages in Michoacán, Mexico

    NARCIS (Netherlands)

    Ruiz-Izaguirre, E.; Eilers, C.H.A.M.; Bokkers, E.A.M.; Ortolani, A.; Ortega-Pacheco, A.; Boer, I.J.M.

    2014-01-01

    tIn Mexican villages, most households keep dogs that roam freely. Therefore, socialisationof village dogs occurs in a different context than that of companion dogs in developedcountries. The objectives of this study were: (1) to assess village dogs’ behavioural responsestowards familiar and

  10. How dogs drink water

    Science.gov (United States)

    Gart, Sean; Socha, Jake; Vlachos, Pavlos; Jung, Sunghwan

    2014-11-01

    Animals with incomplete cheeks (i.e. dogs and cats) need to move fluid against gravity into the body by means other than suction. They do this by lapping fluid with their tongue. When a dog drinks, it curls its tongue posteriorly while plunging it into the fluid and then quickly withdraws its tongue back into the mouth. During this fast retraction fluid sticks to the ventral part of the curled tongue and is drawn into the mouth due to inertia. We show several variations of this drinking behavior among many dog breeds, specifically, the relationship between tongue dynamics and geometry, lapping frequency, and dog weight. We also compare the results with the physical experiment of a rounded rod impact onto a fluid surface. Supported by NSF PoLS #1205642.

  11. Vestibulovaginal stenosis in dogs: 18 cases (1987-1995).

    Science.gov (United States)

    Kyles, A E; Vaden, S; Hardie, E M; Stone, E A

    1996-12-01

    To evaluate vestibulovaginal stenosis in dogs. Retrospective study. 18 dogs with vestibulovaginal stenosis diagnosed between January 1987 and June 1995. Signalment, results of physical examination, and diagnostic testing, treatment, and outcome were analyzed. Mean age at initial examination was 4.6 years. Problems reported by the owners included signs of chronic urinary tract infection (6 dogs), urinary incontinence (4), failure to mate (4), signs of chronic vaginitis (2), and inappropriate urination (1). One dog did not have evidence of a clinical problem. Vestibulovaginal stenosis was detected by means of digital vaginal examination (18/18 dogs), vaginoscopy (17/17 dogs), and positive-contrast vaginography (9/10 dogs). Bacteria were isolated from the urine of 11 of 15 dogs. Twelve of 18 dogs were treated. Manual dilation (4 dogs) and T-shaped vaginoplasty (4) were less successful than vaginectomy (2) or resection of the stenotic area (3). Four of 6 dogs with signs of recurrent urinary tract infection underwent surgical correction, and none of these dogs subsequently had urinary tract infection. Three of 4 dogs with urinary incontinence responded to medical or surgical treatment for sphincter incompetence or for ectopic ureters. Surgical correction of vestibulovaginal stenosis is indicated in dogs that have mating difficulties or signs of recurrent urinary tract infection or chronic vaginitis, but stenosis is probably an incidental finding in most dogs with urinary incontinence. Vaginectomy and vaginal resection and anastomosis are the preferred surgical options.

  12. Pathological features of polyneuropathy in three dogs.

    Science.gov (United States)

    Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

    2013-01-01

    Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.

  13. Surgical treatment of pulmonic stenosis in dogs under cardiopulmonary bypass: outcome in nine dogs.

    Science.gov (United States)

    Bristow, P; Sargent, J; Luis Fuentes, V; Brockman, D

    2018-01-01

    To describe the outcome for nine dogs with pulmonic stenosis treated by open patch grafting using expanded polytetrafluoroethylene under cardiopulmonary bypass. Data were collected from the hospital records of all dogs that had undergone right ventricular outflow tract grafting with an expanded polytetrafluoroethylene patch under cardiopulmonary bypass between 2006 and 2012 for the treatment of pulmonic stenosis. Echocardiographic images were reviewed and the pressure gradient across the right ventricular outflow tract re-measured. Owners of dogs still alive at the time of writing were invited to return to the hospital for reassessment. Nine dogs met the inclusion criteria. Median pressure gradient preoperatively was 118 mmHg, (range 102 to 259 mmHg) reducing to a median of 20 mmHg (range 7 to 53 mmHg) at 48 hours postoperatively and 14 mmHg (range 10 to 70 mmHg), with a median percentage reduction of 89% (range 41 to 94%) at long-term follow-up. Eight of nine dogs survived surgery, with six of nine surviving to hospital discharge. Two dogs were still alive over 6 and 8 years postoperatively. No long-term deaths were believed to be attributable to pulmonic stenosis. Expanded polytetrafluoroethylene patch grafting of the right ventricular outflow tract for treatment of severe pulmonic stenosis in dogs is feasible and can be an effective method to reduce the severity of right ventricular outflow tract obstruction. © 2017 British Small Animal Veterinary Association.

  14. A stimulator of proliferation of spleen colony-forming cells (CFU-S) in the bone marrow of irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Ivanovic, Z.; Milenkovic, P.; Stojanovic, N.; Lukic, M.; Kataranovski, M.

    1993-07-01

    The presence and activity of a spleen colony - forming cell (CFU-S) proliferation stimulator was investigated in rat bone marrow after irradiation. The dose dependent increase in cytosine arabinoside induced cell dealth of normal mouse bone marrow. The results demonstrate the existence of a CFU-S proliferation stimulator in rat bone marrow similar to that originally found as a macrophage product in regenarating mouse bone marrow. The CFU-S proliferation stimulator activity was not associated with the presence of interleukin - 1,2, or 6 like activities in the material tested.

  15. Control of Hemotropic Diseases of Dogs.

    Science.gov (United States)

    1977-12-31

    isolant. Inoculated dogs develo- ped signs of the disease which included fever , weight loss, lym- phodenopathy, corneal opacity, and pancytopenia. Of...in Alsatian dogs infected with E. canis, was not seen in thesedogs; however, 2 dogs devel- oped cutaneous petechial and ecchymotic hemorrhages at...included fever , weight loss, lymphadenopathy, - -- 19 corneal opacity, and pancytopenia. Of 3 dogs that died during the course of the study, one died with

  16. Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Hukkanen, Renee R.; Lawson, Marie; Martin, Greg [The Dow Chemical Company, Midland, MI 48640 (United States); Gilger, Brian [North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606 (United States); Soldatow, Valerie [University of North Carolina, Department of Environmental Sciences and Engineering, Chapel Hill, NC 27599 (United States); LeCluyse, Edward L. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Budinsky, Robert A.; Rowlands, J. Craig [The Dow Chemical Company, Midland, MI 48640 (United States); Thomas, Russell S., E-mail: RThomas@thehamner.org [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States)

    2013-10-15

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular

  17. Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Hukkanen, Renee R.; Lawson, Marie; Martin, Greg; Gilger, Brian; Soldatow, Valerie; LeCluyse, Edward L.; Budinsky, Robert A.; Rowlands, J. Craig; Thomas, Russell S.

    2013-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular

  18. Protective effects of seahorse extracts in a rat castration and testosterone-induced benign prostatic hyperplasia model and mouse oligospermatism model.

    Science.gov (United States)

    Xu, Dong-Hui; Wang, Li-Hong; Mei, Xue-Ting; Li, Bing-Ji; Lv, Jun-Li; Xu, Shi-Bo

    2014-03-01

    This study investigated the effects of seahorse (Hippocampus spp.) extracts in a rat model of benign prostatic hyperplasia (BPH) and mouse model of oligospermatism. Compared to the sham operated group, castration and testosterone induced BPH, indicated by increased penile erection latency; decreased penis nitric oxide synthase (NOS) activity; reduced serum acid phosphatase (ACP) activity; increased prostate index; and epithelial thickening, increased glandular perimeter, increased proliferating cell nuclear antigen (PCNA) index and upregulation of basic fibroblast growth factor (bFGF) in the prostate. Seahorse extracts significantly ameliorated the histopathological changes associated with BPH, reduced the latency of penile erection and increased penile NOS activity. Administration of seahorse extracts also reversed epididymal sperm viability and motility in mice treated with cyclophosphamide (CP). Seahorse extracts have potential as a candidate marine drug for treating BPH without inducing the side effects of erectile dysfunction (ED) or oligospermatism associated with the BPH drug finasteride. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

    Science.gov (United States)

    Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

    2008-01-01

    Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

  20. Personality consistency in dogs: a meta-analysis.

    Science.gov (United States)

    Fratkin, Jamie L; Sinn, David L; Patall, Erika A; Gosling, Samuel D

    2013-01-01

    Personality, or consistent individual differences in behavior, is well established in studies of dogs. Such consistency implies predictability of behavior, but some recent research suggests that predictability cannot be assumed. In addition, anecdotally, many dog experts believe that 'puppy tests' measuring behavior during the first year of a dog's life are not accurate indicators of subsequent adult behavior. Personality consistency in dogs is an important aspect of human-dog relationships (e.g., when selecting dogs suitable for substance-detection work or placement in a family). Here we perform the first comprehensive meta-analysis of studies reporting estimates of temporal consistency of dog personality. A thorough literature search identified 31 studies suitable for inclusion in our meta-analysis. Overall, we found evidence to suggest substantial consistency (r = 0.43). Furthermore, personality consistency was higher in older dogs, when behavioral assessment intervals were shorter, and when the measurement tool was exactly the same in both assessments. In puppies, aggression and submissiveness were the most consistent dimensions, while responsiveness to training, fearfulness, and sociability were the least consistent dimensions. In adult dogs, there were no dimension-based differences in consistency. There was no difference in personality consistency in dogs tested first as puppies and later as adults (e.g., 'puppy tests') versus dogs tested first as puppies and later again as puppies. Finally, there were no differences in consistency between working versus non-working dogs, between behavioral codings versus behavioral ratings, and between aggregate versus single measures. Implications for theory, practice, and future research are discussed.

  1. Personality consistency in dogs: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jamie L Fratkin

    Full Text Available Personality, or consistent individual differences in behavior, is well established in studies of dogs. Such consistency implies predictability of behavior, but some recent research suggests that predictability cannot be assumed. In addition, anecdotally, many dog experts believe that 'puppy tests' measuring behavior during the first year of a dog's life are not accurate indicators of subsequent adult behavior. Personality consistency in dogs is an important aspect of human-dog relationships (e.g., when selecting dogs suitable for substance-detection work or placement in a family. Here we perform the first comprehensive meta-analysis of studies reporting estimates of temporal consistency of dog personality. A thorough literature search identified 31 studies suitable for inclusion in our meta-analysis. Overall, we found evidence to suggest substantial consistency (r = 0.43. Furthermore, personality consistency was higher in older dogs, when behavioral assessment intervals were shorter, and when the measurement tool was exactly the same in both assessments. In puppies, aggression and submissiveness were the most consistent dimensions, while responsiveness to training, fearfulness, and sociability were the least consistent dimensions. In adult dogs, there were no dimension-based differences in consistency. There was no difference in personality consistency in dogs tested first as puppies and later as adults (e.g., 'puppy tests' versus dogs tested first as puppies and later again as puppies. Finally, there were no differences in consistency between working versus non-working dogs, between behavioral codings versus behavioral ratings, and between aggregate versus single measures. Implications for theory, practice, and future research are discussed.

  2. Personality Consistency in Dogs: A Meta-Analysis

    Science.gov (United States)

    Fratkin, Jamie L.; Sinn, David L.; Patall, Erika A.; Gosling, Samuel D.

    2013-01-01

    Personality, or consistent individual differences in behavior, is well established in studies of dogs. Such consistency implies predictability of behavior, but some recent research suggests that predictability cannot be assumed. In addition, anecdotally, many dog experts believe that ‘puppy tests’ measuring behavior during the first year of a dog's life are not accurate indicators of subsequent adult behavior. Personality consistency in dogs is an important aspect of human-dog relationships (e.g., when selecting dogs suitable for substance-detection work or placement in a family). Here we perform the first comprehensive meta-analysis of studies reporting estimates of temporal consistency of dog personality. A thorough literature search identified 31 studies suitable for inclusion in our meta-analysis. Overall, we found evidence to suggest substantial consistency (r = 0.43). Furthermore, personality consistency was higher in older dogs, when behavioral assessment intervals were shorter, and when the measurement tool was exactly the same in both assessments. In puppies, aggression and submissiveness were the most consistent dimensions, while responsiveness to training, fearfulness, and sociability were the least consistent dimensions. In adult dogs, there were no dimension-based differences in consistency. There was no difference in personality consistency in dogs tested first as puppies and later as adults (e.g., ‘puppy tests’) versus dogs tested first as puppies and later again as puppies. Finally, there were no differences in consistency between working versus non-working dogs, between behavioral codings versus behavioral ratings, and between aggregate versus single measures. Implications for theory, practice, and future research are discussed. PMID:23372787

  3. Behavioural changes in dogs treated with corticosteroids.

    Science.gov (United States)

    Notari, Lorella; Burman, Oliver; Mills, Daniel

    2015-11-01

    In human medicine, psychiatric side effects among patients on corticosteroid therapy are widely reported, but this appears to have been largely overlooked in the animal literature despite glucocorticoids being widely used in veterinary medicine. Therefore the aim of the current study was to identify possible psycho-behavioural changes in dogs treated with corticosteroids. Two different methodologies were used. Firstly, dog owners were asked to fill a 12 item questionnaire aimed at further validating the initial results of a previous survey relating to changes seen when their dog was receiving corticosteroid treatment. In a second study, a population of dogs undertook behavioural tests aimed at objectively identifying changes when receiving corticosteroid therapy. In the first study, a sample of owners whose dogs were receiving treatment for dermatological, orthopaedic or other conditions evaluated their dogs' behaviour on and off therapy, using a seven point scale. The survey was completed by 44 dog owners with dogs receiving treatment with a range of corticosteroid preparations (mainly prednisolone and methylprednisolone) and 54 dog owners with dogs receiving treatment with other drugs, mainly antibiotics and non-steroidal anti-inflammatory drugs. Dogs under corticosteroid treatment were reported to be significantly less playful, more nervous/restless, more fearful/less confident, more aggressive in the presence of food, more prone to barking, more prone to startle, more prone to reacting aggressively when disturbed, and more prone to avoiding people or unusual situations. In the second study, eleven “treatment” dogs were tested both before and during corticosteroid treatment with either methyl-prednisolone or prednisolone to assess their sensitivity to a potentially aversive sound stimulus. Eleven control dogs were also tested at the same time intervals in the same environment. Dogs were exposed to a brief dog growl while they explored bowls containing food

  4. Circovirus in tissues of dogs with vasculitis and hemorrhage.

    Science.gov (United States)

    Li, Linlin; McGraw, Sabrina; Zhu, Kevin; Leutenegger, Christian M; Marks, Stanley L; Kubiski, Steven; Gaffney, Patricia; Dela Cruz, Florante N; Wang, Chunlin; Delwart, Eric; Pesavento, Patricia A

    2013-04-01

    We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.

  5. A survey of the dog population in rural Bangladesh.

    Science.gov (United States)

    Hossain, Moazzem; Ahmed, Kamruddin; Marma, Aung Swi Prue; Hossain, Sohrab; Ali, Mohammad Azmat; Shamsuzzaman, Abul Khair Mohammad; Nishizono, Akira

    2013-08-01

    Globally, Bangladesh ranks third in the number of human deaths from rabies. Although dogs are the principal known transmitters of rabies and knowledge of dog populations is essential for effective national control and proper planning, dog control programs are scarce in Bangladesh. Our objective was to count dogs in a rural area to understand the dog population of the country. For this purpose we selected six unions of Raipura upazila in Narsingdi district. Dog counting was done by direct observation following accepted guidelines. We determined the mean density of the dog population in Bangladesh to be 14 dog/km(2) (95% CI 3.7, 24) and the human:dog ratio to be 120 (95% CI 55, 184). Our paper contribute to the literature which shows great variation in the human:dog ratio across regions of the developing world. The human:dog ratio depends on the area's human (as well as dog) population, whereas dog density per unit area indicates the true number of dogs. We propose that extrapolating from the human:dog ratios of other regions not be relied upon for estimating dog populations, unless the ratios can be supplemented by actual counts of dogs within the target area. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. The nutritional requirements of exercising dogs.

    Science.gov (United States)

    Hill, R C

    1998-12-01

    The nutrient requirements of canine athletes are unique. Dogs have a greater capacity for fat oxidation than humans both at rest and during exercise. In dogs undertaking endurance exercise, such as sled dogs, high fat (>50% of energy) diets increase stamina and maximize energy production, and high protein (>30% of energy) diets prevent training-induced anemia. Nutrient requirements differ, however, for sprint racing dogs, such as greyhounds. Greyhounds run faster when fed moderately increased dietary fat but run more slowly when dietary protein is increased. Sled dogs have similar energy requirements to other breeds at rest in a thermoneutral environment ( approximately 550W0.75 kJ/d where W is body weight in kg) but may require as much as 4200W0.75 kJ/d during a race. The energy requirement of greyhounds in training, however, is only approximately 600W0.75 kJ/d. There is little information, however, concerning the vitamin, mineral or other nutrient requirements of athletic dogs; most sled dogs and greyhounds are fed "homemade" recipes. These recipes usually include raw meat and represent a health risk. More studies are required to improve the health and performance of working and racing dogs.

  7. High visual acuity revealed in dogs.

    Science.gov (United States)

    Lind, Olle; Milton, Ida; Andersson, Elin; Jensen, Per; Roth, Lina S V

    2017-01-01

    Humans have selectively bred and used dogs over a period of thousands of years, and more recently the dog has become an important model animal for studies in ethology, cognition and genetics. These broad interests warrant careful descriptions of the senses of dogs. Still there is little known about dog vision, especially what dogs can discriminate in different light conditions. We trained and tested whippets, pugs, and a Shetland sheepdog in a two-choice discrimination set-up and show that dogs can discriminate patterns with spatial frequencies between 5.5 and 19.5 cycle per degree (cpd) in the bright light condition (43 cd m-2). This is a higher spatial resolution than has been previously reported although the individual variation in our tests was large. Humans tested in the same set-up reached acuities corresponding to earlier studies, ranging between 32.1 and 44.2 cpd. In the dim light condition (0.0087 cd m-2) the acuity of dogs ranged between 1.8 and 3.5 cpd while in humans, between 5.9 and 9.9 cpd. Thus, humans make visual discrimination of objects from roughly a threefold distance compared to dogs in both bright and dim light.

  8. High visual acuity revealed in dogs.

    Directory of Open Access Journals (Sweden)

    Olle Lind

    Full Text Available Humans have selectively bred and used dogs over a period of thousands of years, and more recently the dog has become an important model animal for studies in ethology, cognition and genetics. These broad interests warrant careful descriptions of the senses of dogs. Still there is little known about dog vision, especially what dogs can discriminate in different light conditions. We trained and tested whippets, pugs, and a Shetland sheepdog in a two-choice discrimination set-up and show that dogs can discriminate patterns with spatial frequencies between 5.5 and 19.5 cycle per degree (cpd in the bright light condition (43 cd m-2. This is a higher spatial resolution than has been previously reported although the individual variation in our tests was large. Humans tested in the same set-up reached acuities corresponding to earlier studies, ranging between 32.1 and 44.2 cpd. In the dim light condition (0.0087 cd m-2 the acuity of dogs ranged between 1.8 and 3.5 cpd while in humans, between 5.9 and 9.9 cpd. Thus, humans make visual discrimination of objects from roughly a threefold distance compared to dogs in both bright and dim light.

  9. Social referencing in dog-owner dyads?

    Science.gov (United States)

    Merola, I; Prato-Previde, E; Marshall-Pescini, S

    2012-03-01

    Social referencing is the seeking of information from another individual to form one's own understanding and guide action. In this study, adult dogs were tested in a social referencing paradigm involving their owner and a potentially scary object. Dogs received either a positive or negative message from the owner. The aim was to evaluate the presence of referential looking to the owner, behavioural regulation based on the owner's (vocal and facial) emotional message and observational conditioning following the owner's actions towards the object. Most dogs (83%) looked referentially to the owner after looking at the strange object, thus they appear to seek information about the environment from the human, but little differences were found between dogs in the positive and negative groups as regards behavioural regulation: possible explanations for this are discussed. Finally, a strong effect of observational conditioning was found with dogs in the positive group moving closer to the fan and dogs in the negative group moving away, both mirroring their owner's behaviour. Results are discussed in relation to studies on human-dog communication, attachment and social learning.

  10. Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs

    Directory of Open Access Journals (Sweden)

    Evan L. MacLean

    2017-09-01

    Full Text Available Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT and vasopressin (AVP—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species—and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs for the measurement of free (unbound and total (free + bound OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

  11. Seroprevalence of Leishmaniasis Among Dogs Living in a Municipal Dog and Cat Shelter in Edirne.

    Science.gov (United States)

    Düzbeyaz, Ayşe; Şakru, Nermin; Töz, Seray

    2016-06-01

    In this study, we aimed to investigate the seroprevalence of canine leishmaniosis among dogs that live in the town center due to a lack of data on the prevalence of canine leishmaniasis (CanL) in Edirne. In the present study, 37 dogs living in a municipal dog and cat shelter in Edirne were screened for leishmaniosis by the ındirect fluorescent antibody test. All samples were found to be seronegative. Our study is a preliminary study for Edirne. We wish to perform a large-scale seroepidemiological study with a larger number of dogs from different regions and identify Phlebotomus species.

  12. I Walk My Dog Because It Makes Me Happy: A Qualitative Study to Understand Why Dogs Motivate Walking and Improved Health

    Science.gov (United States)

    Marvin, Garry; Perkins, Elizabeth

    2017-01-01

    Dog walking is a popular everyday physical activity. Dog owners are generally more active than non-owners, but some rarely walk with their dog. The strength of the dog–owner relationship is known to be correlated with dog walking, and this qualitative study investigates why. Twenty-six interviews were combined with autoethnography of dog walking experiences. Dog walking was constructed as “for the dog”, however, owners represented their dog’s needs in a way which aligned with their own. Central to the construction of need was perceptions of dog personality and behaviour. Owners reported deriving positive outcomes from dog walking, most notably, feelings of “happiness”, but these were “contingent” on the perception that their dogs were enjoying the experience. Owner physical activity and social interaction were secondary bonuses but rarely motivating. Perceptions and beliefs of owners about dog walking were continually negotiated, depending on how the needs of the owner and dog were constructed at that time. Complex social interactions with the “significant other” of a pet can strongly motivate human health behaviour. Potential interventions to promote dog walking need to account for this complexity and the effect of the dog-owner relationship on owner mental wellbeing. PMID:28825614

  13. Influence of long-term treatment of the rat with clebopride on the morphology of the mammary gland.

    Science.gov (United States)

    de Lima, T C; Morato, G S; Loch, S; Tames, D R

    1990-01-01

    The substituted benzamides or orthopramides are used to treat gastrointestinal and psychotic disorders. The orthopramide clebopride, a potent dopaminergic antagonist, blocks emesis in dogs and stereotyped behavior in rodents. Since the release of prolactin is inhibited by dopamine, antidopaminergic drugs may be useful to increase lactation in nursing mothers. The present work examines the morphological and histological alterations produced by long-term treatment of puerperal and virgin female rats with clebopride. Clebopride induced significant hyperplasia of parenchymal secretory units and stimulated milk secretion in both groups of rats. However, only in virgin rats was mammary weight significantly increased.

  14. DOG-SPOT database for comprehensive management of dog genetic research data

    Directory of Open Access Journals (Sweden)

    Sutter Nathan B

    2010-12-01

    Full Text Available Abstract Research laboratories studying the genetics of companion animals have no database tools specifically designed to aid in the management of the many kinds of data that are generated, stored and analyzed. We have developed a relational database, "DOG-SPOT," to provide such a tool. Implemented in MS-Access, the database is easy to extend or customize to suit a lab's particular needs. With DOG-SPOT a lab can manage data relating to dogs, breeds, samples, biomaterials, phenotypes, owners, communications, amplicons, sequences, markers, genotypes and personnel. Such an integrated data structure helps ensure high quality data entry and makes it easy to track physical stocks of biomaterials and oligonucleotides.

  15. Pulmonary infiltration with eosinophils in 14 dogs

    International Nuclear Information System (INIS)

    Corcoran, B.M.; Thoday, K.L.; Henfrey, J.I.; Simpson, J.W.; Burnie, A.G.; Mooney, C.T.

    1991-01-01

    Pulmonary infiltration with eosinophils was diagnosed in 14 dogs, whose age ranged from three months to 13 years. The predominant clinical sign was coughing. Dyspnoea, tachypnoea and pruritus were also observed. An absolute circulating eosinophilia was seen in eight dogs and basophilia in five dogs. Thoracic radiographic changes were variable and were not diagnostic. Bronchoscopic evidence of mild to severe bronchitis was present in 12 dogs. Abnormal numbers of eosinophils were found in bronchoalveolar lavage samples and, or, bronchial washings in all 14 cases, but no significant bacteria were recovered. Respiratory compliance was measured in five dogs and was abnormal in three. Faecal examination for helminth parasites was carried out in four cases, a large ascarid burden being identified in one. Intradermal skin testing was carried out in three dogs but was negative in all cases. Complete remission of signs was achieved with prednisolone in 12 cases with six dogs requiring continuous or repeated treatment. Three dogs died as a direct consequence of progression of the disease

  16. Incorporation of membrane-anchored flagellin or Escherichia coli heat-labile enterotoxin B subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs

    Directory of Open Access Journals (Sweden)

    Yinglin eQi

    2015-03-01

    Full Text Available Rabies remains an important worldwide public health threat, so safe, effective and affordable vaccines are still being sought. Virus-like particle (VLP-based vaccines targeting various viral pathogens have been successfully produced, licensed and commercialized. Here, we designed and constructed two chimeric rabies virus-like particles (cRVLPs containing rabies virus (RABV glycoprotein (G, matrix (M protein, and membrane-anchored flagellin (EVLP-F or Escherichia coli heat-labile enterotoxin B subunit (EVLP-L as molecular adjuvants to enhance the immune response against rabies. The immunogenicity and potential of cRVLPs as novel rabies vaccine were evaluated by intramuscular vaccination in mouse and dog models. Mouse studies demonstrated that both EVLP-F and EVLP-L induced faster and larger virus-neutralizing antibodies (VNA responses and elicited greater numbers of CD4+ and CD8+ T cells secreting IFN-γ or IL-4 compared with a standard rabies VLP (sRVLP containing only G and M. Moreover, cRVLPs recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. EVLP-F induced a strong, specific IgG2a response but not an IgG1 response, suggesting the activation of Th1 class immunity; in contrast, Th2 class immunity was observed with EVLP-L. The significantly enhanced humoral and cellular immune responses induced by cRVLPs provided complete protection against lethal challenge with RABV. Most importantly, dogs vaccinated with EVLP-F or EVLP-L exhibited increased VNA titers in sera and enhanced IFN-γ and IL-4 secretion from peripheral blood mononuclear cells. Taken together, these results illustrate that when incorporated into sRVLP, membrane-anchored flagellin and LTB possess strong adjuvant activity. EVLP-F and EVLP-L induce significantly enhanced RABV-specific humoral and cellular immune responses in both mouse and dog. Therefore, these cRVLPs may be developed as safe and more efficacious rabies vaccine candidate for animals.

  17. Erythroid differentiation and commitment in rat erythroleukemia cells with hypertonic culture conditions.

    OpenAIRE

    Yamaguchi, Y; Kluge, N; Ostertag, W; Furusawa, M

    1981-01-01

    Cell cultures of 7,12-dimethylbenz[a]anthracene-induced rat erythroleukemia can be stimulated to synthesize hemoglobin when cultured in hypertonic media. During hypertonic treatment the intracellular osmotic conditions immediately readjust to those of the extracellular medium. None of the Friend virus-induced mouse erythroleukemia cell lines was inducible for differentiation with the same hypertonic culture conditions used for rat cells. Earliest commitment to erythroid terminal differentiati...

  18. Roaming of dogs in remote Indigenous communities in northern Australia and potential interaction between community and wild dogs.

    Science.gov (United States)

    Bombara, C; Dürr, S; Gongora, J; Ward, M P

    2017-06-01

    To investigate the roaming of Indigenous community dogs and potential interaction with wild dogs and dingoes. Cross-sectional survey and longitudinal follow-up study. Six remote Indigenous communities in Cape York Peninsula and Arnhem Land in northern Australia were selected. Hair samples were collected from community dogs and microsatellite DNA analyses were used to determine hybrid (>10% dingo DNA) status. Dogs were fitted with GPS collars and home range (ha) was estimated during monitoring periods of up to 3 days. In Cape York Peninsula, 6% of the 35 dogs sampled were dingo hybrids, whereas in Arnhem Land 41% of the 29 dogs sampled were hybrids. The median extended home range was estimated to be 4.54 ha (interquartile range, 3.40 - 7.71). Seven community dogs were identified with an estimated home range > 20 ha and home ranges included the bushland surrounding communities. No significant difference in home ranges was detected between hybrid and non-hybrid dogs. Study results provide some evidence (dingo hybridisation, bushland forays) of the potential interaction between domestic and wild dogs in northern Australia. The nature of this interaction needs further investigation to determine its role in disease transmission; for example, in the case of a rabies incursion in this region. © 2017 Australian Veterinary Association.

  19. Testing the social dog hypothesis: are dogs also more skilled than chimpanzees in non-communicative social tasks?

    Science.gov (United States)

    Wobber, Victoria; Hare, Brian

    2009-07-01

    Relative to non-human primates, domestic dogs possess a number of social skills that seem exceptional-particularly in solving problems involving cooperation and communication with humans. However, the degree to which dogs' unusual skills are contextually specialized is still unclear. Here, we presented dogs with a social problem that did not require them to use cooperative-communicative cues and compared their performance to that of chimpanzees to assess the extent of dogs' capabilities relative to those of non-human primates. We tested the abilities of dogs and chimpanzees to inhibit previously learned responses by using a social and a non-social version of a reversal learning task. In contrast to previous findings in cooperative-communicative social tasks, dogs were not more skilled on the social task than the non-social task, while chimpanzees were significantly better in the social paradigm. Chimpanzees were able to inhibit their prior learning better and more quickly in the social paradigm than they were in the non-social paradigm, while dogs took more time to inhibit what they had learned in both versions of the task. These results suggest that the dogs' sophisticated social skills in using human social cues may be relatively specialized as a result of domestication.

  20. Quantitative survey radiographic evaluation of the lumbosacral spine of normal dogs and dogs with degenerative lumbosacral stenosis

    International Nuclear Information System (INIS)

    Mattoon, J.S.; Koblik, P.D.

    1993-01-01

    Survey radiographic studies of the lumbosacral region for 93 normal dogs and for 26 dogs with confirmed degenerative lumbosacral stenosis were reviewed. Normal dogs were divided into 9 groups based on age and body weight. For normal dogs, increasing age and body weight were associated with a decreased ability to extend the lumbosacral joint and with increased incidence and severity of spondylosis. Transitional lumbosacral vertebrae and evidence of lumbosacral disc space collapse were very infrequent findings, and the pivot point for lumbosacral motion was consistently centered over the lumbosacral disc space. Relative to an age/weight matched sub-population of normal dogs, dogs with degenerative lumbosacral stenosis had similar mean normalized lumbosacral vertebral canal height, larger mean neutral lumbosacral angle, decreased extension of the lumbosacral joint, increased flexion of the lumbosacral joint, reduced lumbosacral range of motion, increased lumbosacral dynamic malalignment, higher incidence and severity of spondylosis, higher incidence of transitional vertebrae, and higher incidence of lumbosacral disc space collapse. A logistic model based strictly on radiographic parameters was able to discriminate normal from affected dogs with an overall accuracy rate of 86%

  1. Seroepidemiology of Canine parvovirus infection in dogs

    Directory of Open Access Journals (Sweden)

    Indrawati Sendow

    2004-10-01

    Full Text Available Canine parvovirus is an acute and fatal viral disease in dogs. A total of 209 local, cross breed and breed dogs sera from Kodya Bogor, Kabupaten Bogor, Sukabumi, and Jakarta, had been tested using Haemagglutination Inhibition Test (HI with pig red blood cells. A total of 64 breed and cross breed dogs from Sukabumi and Kodya Bogor, were used as a sentinel dogs to study the epidemiology of Canine parvovirus (CPV infection and its immunological responses caused by vaccination. The results indicated that 78% (95 breed and cross bred dogs and 59% (51 local dogs had antibody to CPV. Sentinel dogs results indicated that dogs had been vaccinated showed antibody response with the varied titre dependant upon prevaccination titre. Low prevaccinated titre gave better response than protective level titre. From 19 puppies observed, Maternal antibodi were still detected until 5 weeks old puppies. First vaccination given at less than 3 months old, should be boosted after 3 months old puppied. Antibodi titre produced by natural infection will keep untill 2 years. These data concluded that the dog condition and time of vaccination will affect the optimum antibody response.

  2. Current trends in dog-human communication:do dogs inform?

    OpenAIRE

    Kaminski, Juliane; Piotti, Patrizia

    2016-01-01

    Domestic dogs are especially skillful at understanding human forms of communication. Evidence suggests that dogs’ skills in this domain might be an adaptation to life with humans and the result of selection processes during domestication. One question that has sparked a lot of research in recent years is to what extent dogs’ communication is in any way comparable to that of human infants. Here, we discuss recent research that has examined the extent to which dogs communicate to inform others....

  3. Extreme hypoxia tolerance of naked mole-rat brain.

    Science.gov (United States)

    Larson, John; Park, Thomas J

    2009-12-09

    Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

  4. Miastenia gravis diagnostic in dogs

    Directory of Open Access Journals (Sweden)

    Adriana Patricia Suraniti

    2010-12-01

    Full Text Available Miastenia Gravis is a neuromuscular disease caused by auto antibodies. Early Clinical and biochemical diagnosis and treatment is demanded in the assurementof quality and time of life in all dogs. In this study we describe the conventional diagnosis methods and therapy in 32 dogs with suspected myasthenia gravis and propose the administration of bromide of piridostigmin as another use full diagnosis method in dogs.

  5. [Primary hyperparathyroidism in the dog. Diagnosis, therapy and postoperative management in 19 dogs].

    Science.gov (United States)

    Jores, K; Kessler, M

    2011-01-01

    Retrospective evaluation of diagnosis and outcome in 20 dogs with primary hyperparathyroidism. In 20 dogs primary hyperparathyroidism was diagnosed and 19 patients were treated via parathyroidectomy, 10 additionally with partial thyroidectomy. Medical records of the dogs were reviewed for signalment, clinical features, laboratory findings and results of histopathologic examination. In some cases postsurgical rehabilitation of calcium metabolism required substitution with calcium and vitamin D preparations. Mean age of the dogs was 11.5 years. The most common clinical signs comprised polydipsia, polyuria, reduced activity, and stiff gait. Laboratory findings were moderate to extensive hypercalcaemia, low or low-normal serum phosphorus concentrations and normal or increased serum parathyroid hormone concentrations. None of the dogs had an elevated parathyroid hormone-related polypeptide level. Histological examination revealed 11 adenomas, six carcinomas and two glandular hyperplasias. Postsurgical management of calcium homeostasis was challenging in some cases. Tumours of the parathyroid gland can be easily treated by parathyroidectomy and usually have a good prognosis. With careful interpretation of laboratory findings of a patient presenting with hypercalcaemia and ruling out other causes of hypercalcaemia diagnosis of primary hyperparathyroidism can be easily achieved and successfully treated byparathyroidectomy.

  6. Laser lithotripsy for removal of uroliths in dogs

    Science.gov (United States)

    Adams, Larry G.; Lulich, Jody P.

    2006-02-01

    Introduction: This study evaluated the ability to fragment and remove naturally occurring uroliths in dogs using a holmium: YAG laser. Methods: Twenty four dogs with naturally occurring uroliths including 10 spayed females and 14 neutered males. The dogs were 8.7 +/- 2.8 years old and weighed 13.7 +/- 8.0 kg. All dogs had bladder stones and 5 male dogs also had urethral stones. In female dogs, cystoscopy was performed using a rigid cystoscope with sheath diameter of 14 to 19 french. Cystoscopy was performed in males dogs using a 7.5 french diameter pediatric ureteroscope. Uroliths were fragmented using a 20 watt Holmium: YAG laser and the fragments were removed by basket extraction and voiding urohydropropulsion. Results: Average laser parameters for urolith fragmentation were 0.7 Joules at 8 Hertz (range: 0.5 to 1.3 Joules at 5 to 13 Hertz). All urolith fragments were successfully removed in all 10 female dogs and 11 of 14 male dogs. In one male dog, the urethra was too small to allow passage of the ureteroscope. In one of the male dogs, the urethral stones were successfully removed by laser lithotripsy, but removal of the bladder stones was performed by cystotomy. There was one complication of urethral perforation during attempts to pass an access sheath transurethrally in a dog with extensive proliferative urethritis. Conclusions: Laser lithotripsy is a safe and effective method of removing bladder and urethral stones in dogs provided the dog is large enough to permit transurethral passage of a cystoscope or ureteroscope.

  7. Spinal epidural empyema in two dogs

    International Nuclear Information System (INIS)

    Dewey, C.W.; Kortz, G.D.; Bailey, C.S.

    1998-01-01

    Extensive, diffuse, epidural spinal cord compression was visualized myelographically in two dogs presented for rapid development of nonambulatory tetraparesis and paraplegia, respectively. Purulent fluid containing bacterial organisms was aspirated percutaneously under fluoroscopic guidance from the epidural space of each dog. One dog responded poorly to aggressive medical therapy, which included installation of an epidural lavage and drainage system. Both dogs were euthanized due to the severe nature of their disorder and the poor prognosis. Spinal epidural empyema (i.e., abscess) is a rare condition in humans and has not been reported previously in the veterinary literature. Spinal epidural empyema should be considered as a differential diagnosis in dogs presenting with painful myelopathies, especially when accompanied by fever

  8. Design and development of a high resolution animal SPECT scanner dedicated for rat and mouse imaging

    International Nuclear Information System (INIS)

    Sajedi, Salar; Zeraatkar, Navid; Moji, Vahideh; Farahani, Mohammad Hossein; Sarkar, Saeed; Arabi, Hossein; Teymoorian, Behnoosh; Ghafarian, Pardis; Rahmim, Arman; Reza Ay, Mohammad

    2014-01-01

    A dedicated small-animal SPECT system, HiReSPECT, was designed and developed to provide a high resolution molecular imaging modality in response to growing research demands. HiReSPECT is a dual-head system mounted on a rotating gantry. The detection system is based on pixelated CsI(Na) scintillator crystals coupled to two Hamamatsu H8500 Position Sensitive Photomultiplier Tubes in each head. Also, a high resolution parallel-hole collimator is applied to every head. The dimensions of each head are 50 mm×100 mm, enabling sufficient transaxial and axial fields-of-view (TFOV and AFOV), respectively, for coverage of the entire mouse in single-bed position imaging. However, a 50 mm TFOV is not sufficient for transaxial coverage of rats. To address this, each head can be rotated by 90 degrees in order to align the larger dimension of the heads with the short body axis, allowing tomographic data acquisition for rats. An innovative non-linear recursive filter was used for signal processing/detection. Resolution recovery was also embedded in the modified Maximum-Likelihood Expectation Maximization (MLEM) image reconstruction code to compensate for Collimator-Detector Response (CDR). Moreover, an innovative interpolation algorithm was developed to speed up the reconstruction code. The planar spatial resolution at the head surface and the image spatial resolutions were 1.7 mm and 1.2–1.6 mm, respectively. The measurements followed by post-processing showed that the observed count rate at 20% count loss is about 42 kcps. The system sensitivity at the collimator surface for heads 1 and 2 were 1.32 cps/µCi and 1.25 cps/µCi, respectively. The corresponding values were 1.18 cps/µCi and 1.02 cps/µCi at 8 cm distance from the collimator surfaces. In addition, whole-body scans of mice demonstrated appropriate imaging capability of the HiReSPECT

  9. N-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils.

    Science.gov (United States)

    Mora-Cartín, Ricardo; Chacón-Díaz, Carlos; Gutiérrez-Jiménez, Cristina; Gurdián-Murillo, Stephany; Lomonte, Bruno; Chaves-Olarte, Esteban; Barquero-Calvo, Elías; Moreno, Edgardo

    2016-06-01

    Brucella abortus is an intracellular pathogen of monocytes, macrophages, dendritic cells, and placental trophoblasts. This bacterium causes a chronic disease in bovines and in humans. In these hosts, the bacterium also invades neutrophils; however, it fails to replicate and just resists the killing action of these leukocytes without inducing significant activation or neutrophilia. Moreover, B. abortus causes the premature cell death of human neutrophils. In the murine model, the bacterium is found within macrophages and dendritic cells at early times of infection but seldom in neutrophils. Based on this observation, we explored the interaction of mouse neutrophils with B. abortus In contrast to human, dog, and bovine neutrophils, naive mouse neutrophils fail to recognize smooth B. abortus bacteria at early stages of infection. Murine normal serum components do not opsonize smooth Brucella strains, and neutrophil phagocytosis is achieved only after the appearance of antibodies. Alternatively, mouse normal serum is capable of opsonizing rough Brucella mutants. Despite this, neutrophils still fail to kill Brucella, and the bacterium induces cell death of murine leukocytes. In addition, mouse serum does not opsonize Yersinia enterocolitica O:9, a bacterium displaying the same surface polysaccharide antigen as smooth B. abortus Therefore, the lack of murine serum opsonization and absence of murine neutrophil recognition are specific, and the molecules responsible for the Brucella camouflage are N-formyl-perosamine surface homopolysaccharides. Although the mouse is a valuable model for understanding the immunobiology of brucellosis, direct extrapolation from one animal system to another has to be undertaken with caution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues.

    Science.gov (United States)

    Peng, Tao; Huang, Bingzhen; Sun, Yao; Lu, Yongbo; Bonewald, Lynda; Chen, Shuo; Butler, William T; Feng, Jerry Q; D'Souza, Rena N; Qin, Chunlin

    2009-01-01

    Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH(2)- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH(2) termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp(181) (corresponding to Asp(197) of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH(2) terminus of Asp(197) of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp(197) is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp(197) with Ala(197) by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH(2) terminus of Asp(197) is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH(2)-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser(74) in rat DMP1 (Ser(89) in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser(89), we substituted Ser(89) by Gly(89). Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser(89) in mouse DMP1. Copyright 2008 S. Karger AG, Basel.

  11. Differential effects of orally versus parenterally administered qinghaosu derivative artemether in dogs.

    Science.gov (United States)

    Classen, W; Altmann, B; Gretener, P; Souppart, C; Skelton-Stroud, P; Krinke, G

    1999-11-01

    Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Previous animal safety studies with Qinghaosu derivatives revealed dose-dependent neurotoxicity with movement disturbances and neuropathic changes in the hindbrain of intramuscularly treated dogs, rats and monkeys. Such effects have not been seen in man. The objective of our present studies was to compare the effects of high levels of AM administered to dogs p.o. versus i.m. In a pilot study 20 mg/kg/day of AM was given i.m. to groups of 3 male Beagle dogs for 5 and 30 days, respectively. Clinical signs of neurotoxicity were noted in some individual dogs from test day 23 on. One dog had to be sacrificed pre-term. Hematologic findings indicated a hypochromic, microcytic anemia. Microscopic examination demonstrated neuropathic changes only at 30 days, but not at 5 days. The animals had neuronal and secondary axonal damage, most prominent in the cerebellar roof, pontine and vestibular nuclei, and in the raphe/paralemniscal region. The affected neurons showed loss of Nissl substance, cytoplasmic eosinophilia, shrinkage of the nucleus and in advanced stages scavenging by microglia. In a subsequent experiment, AM was administered to groups of 4 male and 4 female dogs, respectively, at 8 daily doses of 0, 20, 40 and 80 mg/kg i.m., or 0, 50, 150 and 600 mg/kg p.o. Neurologic signs were seen at high i.m. doses only. In most animals they were inconspicuous and consisted of reduced activity with convulsions seen in single dogs shortly before death. Neuronal damage occurred in all animals at 40 and 80 mg/kg following i.m. treatment. At 20 mg/kg minimal effects occurred in 5

  12. The 5T mouse multiple myeloma model: Absence of c-myc oncogene rearrangement in early transplant generations

    NARCIS (Netherlands)

    Radl, J.; Punt, Y.A.; Enden-Vieveen, M.H.M. van den; Bentvelzen, P.A.J.; Bakkus, M.H.C.; Akker T., W. van den; Benner, R.

    1990-01-01

    Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobulin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM),

  13. "Like owner, like dog": correlation between the owner's attachment profile and the owner-dog bond.

    Science.gov (United States)

    Siniscalchi, Marcello; Stipo, Carlo; Quaranta, Angelo

    2013-01-01

    During recent years, several studies have revealed that human-dog relationships are based on a well-established and complex bond. There is now evidence suggesting that the dog-human affectional bond can be characterized as an "attachment". The present study investigated possible association between the owners' attachment profile assessed throughout a new semi-projective test (the 9 Attachment Profile) and the owner-dog attachment bond evaluated using a modified version of those used in studying human infants: Ainsworth's "strange situation". The findings represented the first evidence for the presence of a correlation between the owners' attachment profile and the owner-dog attachment bond throughout procedure and behavioural analyses involving controlled observations.

  14. "What Are All These Dogs Doing at School?" Using Therapy Dogs to Promote Children's Reading Practice

    Science.gov (United States)

    Jalongo, Mary Renck

    2005-01-01

    This article discusses how registered therapy dogs can motivate and support children as they practice reading aloud in the company of the dog and with the support of the dog's handler. It also offers practical advice to educators, librarians, administrators, and community members seeking to implement such a program in their communities.

  15. Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat

    Science.gov (United States)

    Meiri, Noam; Ghelardini, Carla; Tesco, Giuseppina; Galeotti, Nicoletta; Dahl, Dennis; Tomsic, Daniel; Cavallaro, Sebastiano; Quattrone, Alessandro; Capaccioli, Sergio; Bartolini, Alessandro; Alkon, Daniel L.

    1997-01-01

    Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic “knockouts”. PMID:9114006

  16. Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.

    Science.gov (United States)

    Meiri, N; Ghelardini, C; Tesco, G; Galeotti, N; Dahl, D; Tomsic, D; Cavallaro, S; Quattrone, A; Capaccioli, S; Bartolini, A; Alkon, D L

    1997-04-29

    Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".

  17. Cuttable plate fixation for small breed dogs with radius and ulna fractures: Retrospective study of 31 dogs.

    Science.gov (United States)

    Watrous, Gwyneth K; Moens, Noel M M

    2017-04-01

    This retrospective study evaluated complication rates for radius and ulna fractures in small breed dogs in which 1.5 mm to 2.7 mm cuttable bone plates were used for internal fixation. The medical records of all cases from 2004 to 2011 that were presented to our clinic were reviewed. Inclusion criteria were: dogs with body weight dogs met the inclusion criteria. Of 25 dogs that were available for follow-up, all achieved union, minor complications occurred in 9, and major complications occurred in 8. External coaptation was responsible for complications in 8 cases and the need for coaptation needs to be investigated. Excluding minor complications, 32% of patients required at least 1 additional surgery or additional hospitalization. All but 2 of the dogs returned to full function. The 1.5 mm straight plate was successfully used in all dogs with a body weight of 0.9 to 2.6 kg.

  18. Gallbladder Agenesis in 17 Dogs: 2006-2016.